When we think about menopause, many of us imagine it’s something to worry about later. But understanding menopause—especially your genetic predisposition for early menopause—can actually help you stay ahead of your health today. Whether menopause isn&#8217;t on your radar or you&#8217;re already navigating the transition, being informed is a powerful way to care for your future (and current!) well-being.



Natural menopause marks the end of menstrual cycles and happens when you&#8217;ve gone 12 months without a period. Most people experience it between ages 45 and 55, but it&#8217;s considered early if it happens before age 45.



Early menopause can be triggered by medical treatments like chemotherapy, radiation, or surgery that removes the ovaries, or can occur naturally influenced by your genetics. That’s why understanding your genetic risk is so important. To support this, we’ve launched the new Early Menopause* report for female <a href="https://www.23andme.com/membership/" target="_blank" rel="noreferrer noopener">23andMe+ Premium</a>™ members, offering insights into your genetic predisposition.



<h2 class="wp-block-heading" id="h-why-you-should-care-now">Why You Should Care Now</h2>



Even though early menopause isn’t something you can always predict or prevent, there are things you can do to stay informed and in control:



<ul class="wp-block-list">
<li>Learn About Your Genetic Predisposition. Finding out if your genetics predispose you to experiencing menopause earlier can help you make more informed decisions before symptoms start.</li>



<li>Know Your Family History. Talk to your mom, aunts, or older sisters about when they started menopause. If it happened early for them, it might be worth discussing with your doctor sooner than later.</li>



<li>Preserve Your Fertility (If That’s a Goal). If you’re concerned about future fertility, it’s okay to start that conversation early. Options like egg freezing can offer peace of mind and flexibility.</li>



<li>Support Your Overall Health. Quit smoking, if you smoke—it&#8217;s linked to an increased risk of early menopause. Maintain a healthy weight, especially avoiding being underweight, which can increase your risk. And eat a healthy diet: think whole grains, leafy greens, lean proteins, and healthy fats like avocado or olive oil. </li>
</ul>



<h2 class="wp-block-heading" id="h-understanding-perimenopause-the-lead-up-to-menopause">Understanding Perimenopause: The Lead-Up to Menopause</h2>



Perimenopause is the transition period that starts 2–10 years before menopause. Symptoms of perimenopause can be subtle or non-specific, and many people don&#8217;t expect symptoms to appear until later in their lives. Knowing your genetic predisposition can help you be aware of when you might start experiencing symptoms.&nbsp;



Here&#8217;s what to look out for:



<ul class="wp-block-list">
<li>Irregular or missed periods</li>



<li>Hot flashes or night sweats</li>



<li>Trouble sleeping</li>



<li>Mood changes or irritability</li>



<li>Vaginal dryness or lower libido</li>
</ul>



Keep a symptom tracker or use a health app to log your menstrual cycle, mood changes, and physical symptoms. Noticing patterns early can help you and your healthcare provider take action before symptoms intensify.



<h2 class="wp-block-heading" id="h-already-in-menopause-or-experiencing-it-early-here-s-what-you-can-do-now">Already in Menopause or Experiencing It Early? Here’s What You Can Do Now</h2>



If you’ve already entered menopause (early or otherwise), you’re not alone—and there are plenty of tools and strategies to help you feel your best.



<ul class="wp-block-list">
<li>Hormone therapy (MHT/HRT) may ease symptoms like hot flashes and protect heart and bone health. Talk to your provider to see if it’s a good fit for you.</li>



<li>Lifestyle changes like stress reduction, yoga, or meditation can help with emotional ups and downs.</li>



<li>Moisturizers or vaginal estrogen can help with dryness and intimacy discomfort.</li>



<li>Emotional Support: Menopause can be emotional—especially if it happens early or unexpectedly. Connecting with friends and support groups, a therapist or counselor, or online communities or forums can help you feel heard and supported.</li>
</ul>



<h3 class="wp-block-heading" id="h-protecting-your-health-for-the-long-haul">Protecting Your Health for the Long Haul</h3>



After menopause, your body produces less estrogen and progesterone, which can affect your bones, heart, and brain. But there’s plenty you can do to stay strong and vibrant:



<ul class="wp-block-list">
<li>Get moving: Weight-bearing exercise (like walking, dancing, or lifting light weights) keeps bones strong.</li>



<li>Eat for your heart: A diet rich in fruits, vegetables, whole grains and healthy fats, supports long-term health.</li>



<li>Get your calcium and vitamin D: These vitamins are especially important for your bones post-menopause.</li>



<li>Check in with your doctor: Schedule annual physicals and get any recommended scans or checks. If considering MHT, experts recommend starting it before age 60 or within 10 years of menopause onset to get the most benefit.</li>
</ul>



<h2 class="wp-block-heading" id="h-be-your-own-health-advocate">Be Your Own Health Advocate</h2>



Menopause doesn’t have to be a mystery—or something to fear. Whether you&#8217;re years away, noticing symptoms now, or already postmenopausal, knowledge is power. Staying connected to your body, prioritizing your mental and physical health, and talking to trusted healthcare providers can make all the difference.



<figure class="wp-block-image aligncenter size-full is-resized"><img loading="lazy" decoding="async" width="612" height="252" src="http://35.88.189.111/wp-content/uploads/2025/06/early-menopause.png" alt="" class="wp-image-34008" style="width:381px;height:auto" srcset="https://blogcms.23andme.com/wp-content/uploads/2025/06/early-menopause.png 612w, https://blogcms.23andme.com/wp-content/uploads/2025/06/early-menopause-300x124.png 300w" sizes="auto, (max-width: 612px) 100vw, 612px" /></figure>



Your wellness journey is yours—and you deserve to feel supported, strong, and informed every step of the way.



<h2 class="wp-block-heading" id="h-learn-more">Learn more</h2>



Eligible 23andMe members can view this report with their other Health Predisposition reports.



Not a 23andMe+ Premium member yet? Learn more about what 23andMe has to offer <a href="https://www.23andme.com/membership/" target="_blank" rel="noreferrer noopener">here</a>.



<hr class="wp-block-separator has-text-color has-foreground-color has-alpha-channel-opacity has-foreground-background-color has-background"/>



NOTE: Within this blog post, we use the word “female” to refer to people whose birth sex is female. However, we recognize that not everyone who experiences menopause will identify as female and being categorized by birth sex may be an uncomfortable experience for some people. We do not mean to delegitimize anyone’s gender identity. Learn more about why we made this decision in this <a href="https://customercare.23andme.com/hc/en-us/articles/360010964373-How-23andMe-Uses-Your-Genetic-Sex-Birth-Sex-and-Gender" target="_blank" rel="noreferrer noopener">help article</a>.



* The 23andMe Early Menopause PRS report is based on a genetic model that includes data and insights from 23andMe consented research participants and incorporates more than 2,000 genetic variants to provide information on the likelihood of developing early menopause. The report does not describe a person’s overall likelihood, does not account for lifestyle or family history and has not been reviewed by the US Food and Drug Administration. The Early Menopause PRS report is not intended to tell you anything about your current state of health, or to be used to make medical decisions or determine any treatment.

23andMe Blog

23andMe Blog Team

Menopause Isn’t Just for “Later” – What You Should Know Now

Thyroid disease is surprisingly common. Studies have estimated that around 1 in 20 people in the U.S. have hypothyroidism or hyperthyroidism, some of the most common thyroid conditions.[1,2] Yet despite how prevalent thyroid disease is, it&#8217;s also frequently missed. According to the American Thyroid Association, up to 60% of people with a thyroid condition are unaware of it.[3]



<h2 class="wp-block-heading" id="h-thyroid-101">Thyroid 101</h2>



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="422" src="http://35.88.189.111/wp-content/uploads/2025/05/hashimotos-report-icon-1024x422.png" alt="" class="wp-image-33934" srcset="https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon-1024x422.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon-300x124.png 300w, https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon-768x316.png 768w, https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon-880x362.png 880w, https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon-1180x486.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2025/05/hashimotos-report-icon.png 1224w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



The thyroid is a butterfly-shaped organ in the neck, just in front of the trachea, that <a href="https://www.23andme.com/topics/health-predispositions/hashimotos-disease/?srsltid=AfmBOoqCPT1mfxaBMpCBrjlJJP_jB7OXbGh7CJ03xS9Njaw1R4tjhA-H" target="_blank" rel="noreferrer noopener">despite its small size plays an important role</a> in a range of physiological functions. It produces thyroid hormone, which circulates throughout the body and impacts metabolism, energy levels, and more. If the thyroid is underactive (<a href="https://www.mayoclinic.org/diseases-conditions/hypothyroidism/symptoms-causes/syc-20350284" target="_blank" rel="noreferrer noopener">hypothyroidism</a>), it doesn&#8217;t produce enough thyroid hormone. Conversely, if it&#8217;s overactive (<a href="https://www.mayoclinic.org/diseases-conditions/hyperthyroidism/symptoms-causes/syc-20373659" target="_blank" rel="noreferrer noopener">hyperthyroidism</a>), it produces too much.&nbsp;



The most common causes of both conditions are autoimmune disorders,[4] where the body&#8217;s immune system mistakenly attacks cells in the thyroid.



<h2 class="wp-block-heading" id="h-what-makes-thyroid-diseases-difficult-to-diagnose-nbsp">What makes thyroid diseases difficult to diagnose?&nbsp;</h2>



One factor is that symptoms can be non-specific. With autoimmune hypothyroidism, for instance, <a href="https://my.clevelandclinic.org/health/diseases/17665-hashimotos-disease" target="_blank" rel="noreferrer noopener">symptoms</a> can include things like weight gain, low energy, joint stiffness, and depression — which can easily be mistaken as the result of stress or too much time behind a computer, for example. Plus, symptoms can come on gradually over time. Or symptoms may come and go.&nbsp;



<h2 class="wp-block-heading" id="h-sometimes-it-s-more-than-just-stress">Sometimes it&#8217;s more than just stress</h2>



A common scenario for someone with undiagnosed Hashimoto&#8217;s: you start to notice gradual but unexplained weight gain along with unshakeable fatigue, and decide to double down on diet and exercise. Yet you see little impact of these efforts. That&#8217;s such a common experience — even for those with normal thyroid function — that it might not occur to you, or your doctor, to get a blood test to rule out potential thyroid problems.



The good news is that once they&#8217;re diagnosed, both hypothyroidism and its counterpart, hyperthyroidism, are treatable, though they may demand lifelong attention to managing them.



<h2 class="wp-block-heading" id="h-exploring-the-role-of-genetics">Exploring the role of genetics</h2>



<figure class="wp-block-image alignright size-large is-resized"><img loading="lazy" decoding="async" width="1024" height="845" src="http://35.88.189.111/wp-content/uploads/2018/04/DNA-Discovery-1024x845.png" alt="" class="wp-image-26142" style="width:224px;height:auto" srcset="https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery-1024x845.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery-300x248.png 300w, https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery-768x634.png 768w, https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery-880x726.png 880w, https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery-1180x974.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2018/04/DNA-Discovery.png 1270w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



Like other autoimmune conditions, Hashimoto&#8217;s disease and autoimmune hyperthyroidism (Graves&#8217; disease) have a strong genetic component. It&#8217;s been observed that individuals have a &#8220;set point&#8221; or characteristic level of thyroid hormone,[5] and genetics may explain up to two-thirds of the variation between individuals in this set point.[6]



So could genetics help identify people more likely to experience thyroid conditions? In recent years, research has explored how genetics can be used to predict risk for diseases like Hashimoto&#8217;s using polygenic risk scores, or PRS. Someone with the highest <a href="https://permalinks.23andme.com/pdf/23_21-PRSMethodologyAppendix_2022.pdf" target="_blank" rel="noreferrer noopener">genetic likelihood for Hashimoto&#8217;s disease based on a PRS calculated by 23andMe</a> has a <a href="https://permalinks.23andme.com/pdf/23_21-PRSMethodologyAppendix_2022.pdf">3-6 times higher odds</a> of being diagnosed with this condition than someone with an average genetic likelihood.[7]&nbsp;



Polygenic scores also have promising applications for <a href="https://pubmed.ncbi.nlm.nih.gov/32132206/" target="_blank" rel="noreferrer noopener">predicting risk of thyroid cancer</a>, predicting <a href="https://pubmed.ncbi.nlm.nih.gov/37453101/" target="_blank" rel="noreferrer noopener">subtypes of thyroid cancer</a>, and even improving <a href="https://pubmed.ncbi.nlm.nih.gov/37683082/" target="_blank" rel="noreferrer noopener">AI tools for predicting</a> which thyroid nodules are malignant.&nbsp;



And genomics can help tease apart the <a href="https://pubmed.ncbi.nlm.nih.gov/38291025/" target="_blank" rel="noreferrer noopener">biological mechanisms</a> of thyroid function that underlie all these conditions.



<h2 class="wp-block-heading" id="h-genetics-as-a-tool-for-awareness-and-early-action">Genetics as a tool for awareness and early action</h2>



Genetic insights can reveal an increased susceptibility to thyroid conditions, empowering individuals to be more proactive about their health. This heightened awareness could pave the way for faster diagnoses and earlier treatments. And that translates to more years of good health.



_____________________________________________________________________



References:



[1]Doubleday AR et al. (2020). &#8220;Hyperthyroidism.&#8221; Gland Surg. 9(1):124-135. <a href="https://pubmed.ncbi.nlm.nih.gov/32206604/" target="_blank" rel="noreferrer noopener">https://pubmed.ncbi.nlm.nih.gov/32206604/</a>&nbsp;



[2]Patil N et al. (2024). &#8220;Hypothyroidism&#8221;. StatPearls [Internet]. Accessed May 19, 2025, from <a href="https://www.ncbi.nlm.nih.gov/books/NBK519536/" target="_blank" rel="noreferrer noopener">https://www.ncbi.nlm.nih.gov/books/NBK519536/</a>.



[3]American Thyroid Association. &#8220;General Information/Press Room.&#8221; Accessed May 19, 2025, from <a href="https://www.thyroid.org/media-main/press-room/" target="_blank" rel="noreferrer noopener">https://www.thyroid.org/media-main/press-room/</a>.&nbsp;



[4]Vanderpump MP. (2011). &#8220;The epidemiology of thyroid disease.&#8221; Br Med Bull. 99:39-51. <a href="https://pubmed.ncbi.nlm.nih.gov/21893493/" target="_blank" rel="noreferrer noopener">https://pubmed.ncbi.nlm.nih.gov/21893493/</a>&nbsp;



[5]Andersen S et al. (2002). &#8220;Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease.&#8221; J Clin Endocrinol Metab. 87(3):1068-72. <a href="https://pubmed.ncbi.nlm.nih.gov/11889165/" target="_blank" rel="noreferrer noopener">https://pubmed.ncbi.nlm.nih.gov/11889165/</a>



[6]Panicker V. (2011). &#8220;Genetics of thyroid function and disease.&#8221; Clin Biochem Rev. 32(4):165-75. <a href="https://pubmed.ncbi.nlm.nih.gov/22147956/" target="_blank" rel="noreferrer noopener">https://pubmed.ncbi.nlm.nih.gov/22147956/</a>



[7]Ashenhurst JR et al. (2025). &#8220;White Paper 23-21: A generalized method for the creation and evaluation of polygenic scores.&#8221; 23andMe. Accessed May 19, 2025, from <a href="https://permalinks.23andme.com/pdf/23_21-PRSMethodology_May2020.pdf" target="_blank" rel="noreferrer noopener">https://permalinks.23andme.com/pdf/23_21-PRSMethodology_May2020.pdf</a>.

Sr. Product Scientist I

Becca Berns

Today Is World Thyroid Day and Genomics Is Here for It

<h2 class="wp-block-heading" id="h-understanding-osteoporosis-a-common-and-manageable-condition">Understanding osteoporosis: a common and manageable condition</h2>



This week, 23andMe released a new report on <a href="https://you.23andme.com/reports/prs.osteoporosis/">osteoporosis</a> for 23andMe+ Premium members.&nbsp;



Osteoporosis is a condition where bone density becomes too low, making bones more fragile and more likely to break or fracture. According to the <a href="https://www.osteoporosis.foundation/facts-statistics/key-statistic-for-north-america">International Osteoporosis Foundation</a>, about half of females and up to a quarter of males in the U.S. will break a bone due to low bone density.



Osteoporosis is <a href="https://www.niams.nih.gov/health-topics/osteoporosis">sometimes called a “silent disease”</a> because it usually has no symptoms until people break a bone. These breaks – most commonly in the spine, hip, or wrist – can be caused by minor falls, normal activities like bending or lifting, or even spontaneously. Fortunately, osteoporosis is highly actionable if diagnosed early. There are medications that can slow bone loss, and strategies that can help prevent falls.



<figure class="wp-block-image size-full"><img loading="lazy" decoding="async" width="306" height="126" src="http://35.88.189.111/wp-content/uploads/2025/01/PRS-Hero.jpg" alt="icons of broken bone" class="wp-image-33645" srcset="https://blogcms.23andme.com/wp-content/uploads/2025/01/PRS-Hero.jpg 306w, https://blogcms.23andme.com/wp-content/uploads/2025/01/PRS-Hero-300x124.jpg 300w" sizes="auto, (max-width: 306px) 100vw, 306px" /></figure>



<h2 class="wp-block-heading" id="h-the-role-of-dna-in-bone-health">The role of DNA in bone health</h2>



<a href="https://pubmed.ncbi.nlm.nih.gov/35478046/">According to published data</a>, it&#8217;s estimated that genetics explains ~60-80% of the variability in bone density. Knowing about one&#8217;s genetic likelihood of developing osteoporosis can prompt early conversations with healthcare providers to determine if screening might be appropriate. 



<figure class="wp-block-image size-full"><img loading="lazy" decoding="async" width="416" height="234" src="http://35.88.189.111/wp-content/uploads/2025/01/Ways-to-Take-Action.png" alt="" class="wp-image-33646" srcset="https://blogcms.23andme.com/wp-content/uploads/2025/01/Ways-to-Take-Action.png 416w, https://blogcms.23andme.com/wp-content/uploads/2025/01/Ways-to-Take-Action-300x169.png 300w" sizes="auto, (max-width: 416px) 100vw, 416px" /></figure>



<h3 class="wp-block-heading" id="h-ways-to-take-action">Ways to take action</h3>



It can also help to implement strategies to avoid falls and to take preventative measures such as:



<ul class="wp-block-list">
<li> making exercise (especially weight-bearing exercise) part of your daily routine</li>



<li>eating a healthy diet with plenty of vitamin D and calcium</li>



<li>maintaining a healthy weight (being underweight is associated with increased risk) </li>



<li>avoiding alcohol and smoking.</li>
</ul>



<h2 class="wp-block-heading" id="h-about-the-23andme-osteoporosis-report">About the 23andMe Osteoporosis report</h2>



23andMe+ Premium’s new Osteoporosis report* estimates one’s genetic likelihood of osteoporosis using a statistical model known as a polygenic risk score (PRS). The report uses an individual’s genetic results at many genetic markers, along with their genetic ancestry and birth sex, to estimate the likelihood of developing osteoporosis. The Osteoporosis report was developed by 23andMe scientists and clinical experts using data from 23andMe’s customers who consented to participate in research.



A published<a href="https://permalinks.23andme.com/pdf/23_25-PRSMethodology.pdf"> white paper </a>fully details the science and methodology behind 23andMe’s PRS technology. While the genetic variants included in the report play a role, the report does not account for all factors that could impact a person’s likelihood of developing osteoporosis.



<h2 class="wp-block-heading" id="h-learn-more">Learn more</h2>



 23andMe+ Premium members can view this with their other Health Predisposition reports.



Current 23andMe Health + Ancestry Service customers on the current genotyping chip can receive this and 35+ other reports by joining a 23andMe+ Premium membership within their account.



Not a <a href="https://www.23andme.com/membership/">23andMe+ Premium member</a> yet? Learn more about what <a href="https://www.23andme.com/compare-dna-tests/">23andMe has to offer here</a>.



<hr class="wp-block-separator has-alpha-channel-opacity"/>



NOTE: Within this blog post and the Osteoporosis report, we use the word “male” to refer to people whose birth sex is male and “female” to refer to people whose birth sex is female. However, we recognize that being categorized by birth sex may be an uncomfortable experience for some people, and we do not mean to delegitimize anyone’s gender identity. Learn more about why we made this decision in this <a href="https://customercare.23andme.com/hc/en-us/articles/360010964373-How-23andMe-Uses-Your-Genetic-Sex-Birth-Sex-and-Gender">help article</a>.



* The 23andMe Osteoporosis PRS report is based on a genetic model that includes data and insights from 23andMe consented research participants and incorporates more than 22,000 genetic variants to provide information on the likelihood of developing osteoporosis. The report does not describe a person’s overall likelihood, does not account for lifestyle or family history and has not been reviewed by the US Food and Drug Administration. The Osteoporosis PRS report is not intended to tell you anything about your current state of health, or to be used to make medical decisions or determine any treatment.

A New Report on Osteoporosis

This week, 23andMe released new reports on three of the most common types of cancer — <a href="https://www.cdc.gov/cancer/breast/basic_info/">breast cancer,</a> <a href="https://www.cdc.gov/cancer/prostate/basic_info/">prostate cancer</a>, and <a href="https://www.cdc.gov/cancer/colorectal/basic_info/what-is-colorectal-cancer.htm">colorectal cancer</a>.&nbsp;



The new reports use thousands of genetic variants associated with the disease to assess a person’s likelihood of an individual developing one of these cancers.



The reports are based on statistical models known as polygenic risk scores (PRS), developed by 23andMe through its proprietary research database. These new PRS reports were developed by 23andMe scientists and clinical experts using the company’s massive database of genetic and self-reported health information contributed by consented research participants.



<h2 class="wp-block-heading" id="h-the-new-cancer-prs-reports">The New Cancer PRS Reports</h2>



The new 23andMe PRS reports focus on some of the most common cancers for which genetics are often a factor, noting where some customers may have an increased likelihood of developing these conditions relative to the average. This is important because averages can mask significant differences – some people have a higher chance of developing cancer, and some have a slightly lower chance due to genetics and other factors. Significantly, healthy lifestyle habits can offset an increased genetic likelihood of developing these diseases, while routine screening can help with early detection.



Breast cancer affects, on average, one in eight females, while prostate cancer affects about one in eight males, and colorectal cancer impacts about one in 25 people.



For these reports, depending on the type of cancer and the member’s ancestry, up to 5-to-30 percent of our current <a href="https://www.23andme.com/membership/">23andMe+ Premium</a> and <a href="https://www.23andme.com/total-health/">23andMe+ Total Health</a> members will see an increased likelihood result.&nbsp;



It’s important to note that these three new cancer reports — <a href="https://you.23andme.com/reports/prs.breast_cancer/">Breast Cancer PRS Report</a>*, <a href="https://you.23andme.com/reports/prs.prostate_cancer/">Prostate Cancer PRS Report</a>*, and <a href="https://you.23andme.com/reports/prs.colorectal_cancer/">Colorectal Cancer PRS Report</a>* — augment or work in parallel with three existing Genetic Health Risk reports* that look at select variants associated with these types of cancers.&nbsp;



Although each report examines how a customer’s genetics can impact the chances of developing cancer, the reports differ in several ways. One way to look at them is to consider the different causes of cancer.



Cancer can be caused by rare genetic variants that have a significant impact on the risk of developing cancer. These highly impactful variants are part of our Genetic Health Risk reports. Other times, cancer can be influenced by thousands of common variants that each have a small effect on the likelihood of developing cancer. But a lot of small impact variants can make a big impact. 23andMe’s new PRS reports consider many common variants to report the likelihood of developing cancer. It’s these common genetic variants combined with lifestyle and environment that cause the majority of cancer.



23andMe’s existing Genetic Health Risk reports include the <a href="https://blog.23andme.com/articles/23andme-updates-brca1-2-report">BRCA1/BRCA2 (Selected Variants)</a>* report, the <a href="https://blog.23andme.com/articles/23andmes-new-hereditary-prostate-cancer-hoxb13-related-report">Hereditary Prostate Cancer (HOXB13-Related)</a>* report, and the <a href="https://blog.23andme.com/articles/23andmes-new-mutyh-report">MUTYH-Associated Polyposis (MAP)</a>* report. If a customer has an increased risk detected in one of those reports, they will not receive a result for the related PRS report.



<h2 class="wp-block-heading" id="h-a-caveat-regarding-the-new-colorectal-cancer-report">A Caveat Regarding the New Colorectal Cancer Report</h2>



The new colorectal cancer PRS report is only available for those of European and Latino/Hispanic descent, as there is not yet enough data to provide a result for those of other ethnicities &#8211; a historical issue with genetic research and polygenic scores at large. As the number of customers opting to participate in our research grows, we may be able to improve the model performance within these groups.&nbsp;



To help address this issue, 23andMe recently launched <a href="https://www.23andme.com/genetic-insights-into-colorectal-cancer-black-community/">Genetic Insights into Colorectal Cancer in the Black Community</a> study, which invites individuals with African ancestry and/or who identify as Black or African American to participate. In the U.S., Black and African Americans have an increased chance of developing and dying from colorectal cancer compared to many other ethnic groups. We hope to use the insights gained from this study to help more customers understand their chances of developing the disease. In the fall of 2023, we updated our BRCA1/BRCA2 (selected variants) report to include 44 variants and improve its coverage for people of non-European ancestry.&nbsp;



<h2 class="wp-block-heading" id="h-find-out-more-about-23andme-s-new-cancer-prs-nbsp">Find Out More About 23andMe’s New Cancer PRS&nbsp;</h2>



The hope is that these new PRS reports will help our customers become more informed, alerting them to an increased likelihood of developing cancer that they would not have known otherwise.



The three new PRS reports are available to <a href="https://www.23andme.com/membership/">23andMe+ Premium</a> members and <a href="https://www.23andme.com/total-health/">23andMe+ Total Health</a> members. Because these three new cancer reports cover similar conditions covered in three of our previously released sensitive reports—BRCA1/BRCA2 (Selected Variants), Hereditary Prostate Cancer (HOXB13-Related), and MUTYH-Associated Polyposis—we require customers to opt-in and view any tutorials associated with those sensitive reports in order to view their new cancer reports.&nbsp;



While the new reports do not include suggestions for clinical action and do not diagnose cancer, they do highlight healthy lifestyle habits, the importance of keeping up to date with screening, and what to discuss with your healthcare provider.



<h2 class="wp-block-heading" id="h-learn-more">Learn More</h2>



23andMe+ Premium members can find links to three new PRS reports on the new topic pages.



<ul class="wp-block-list">
<li><a href="https://you.23andme.com/health/condition/breast_cancer/">Breast Cancer </a>(only available for customers who self-reported their birth sex as female)</li>



<li><a href="https://you.23andme.com/health/condition/prostate_cancer/">Prostate Cancer </a>(only available for customers who self-reported their birth sex as male)</li>



<li><a href="https://you.23andme.com/health/condition/colorectal_cancer/">Colorectal Cancer&nbsp;</a></li>
</ul>



These new topic pages explain how the new cancer reports work with 23andMe’s existing Genetic Health Risk reports. In addition, the pages include information about the factors influencing the chances of developing one of these cancers and the importance of knowing your family health history.



These new topic pages will also be available to all 23andMe <a href="https://www.23andme.com/dna-health-ancestry/">Health + Ancestry customers</a> on the <a href="https://customercare.23andme.com/hc/en-us/articles/218392668-Upgrading-to-23andMe-s-Newest-Chip-Version">latest genotyping chip</a>, V5.&nbsp;



Find out all that 23andMe has to offer and <a href="https://www.23andme.com/compare-dna-tests/">compare our services here</a>.



<hr class="wp-block-separator has-alpha-channel-opacity"/>



<h2 class="wp-block-heading" id="h-disclaimer">Disclaimer</h2>



*The 23andMe PGS test includes health predisposition and carrier status reports. Health predisposition reports include both reports that meet FDA requirements for genetic health risks and PRS reports which are based on a statistical model that includes data and insights from 23andMe consented research participants, and have not been reviewed by the FDA. 



The test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks and reporting carrier status. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. Each PRS report describes if a person has a certain likelihood of developing a condition, but does not describe a person’s overall likelihood. 



The test is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future, the health of your fetus, or your newborn child&#8217;s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. 



<h2 class="wp-block-heading" id="h-warnings-amp-limitations">Warnings &amp; Limitations: </h2>



The 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) is indicated for reporting of 44 variants in the BRCA1 and BRCA2 genes. The report describes if a person&#8217;s genetic result is associated with an increased risk of developing breast cancer and ovarian cancer and may be associated with an increased risk for prostate cancer, pancreatic cancer, and potentially other cancers. 



The variants included in this report do not represent the majority of the BRCA1/BRCA2 variants in people of most ethnicities. The MUTYH-Associated Polyposis Genetic Health Risk Report is indicated for reporting the Y179C and G396D variants in the MUTYH gene and an increased risk for colorectal cancer. The two variants included in this report are most common in people of Northern European descent. The Hereditary Prostate Cancer (HOXB13-Related) Genetic Health Risk report is indicated for reporting the G84E variant in the HOXB13 gene. The report describes if a person has the G84E variant and if a male is at increased risk for prostate cancer. The variant included in this report is most common in people of European descent, especially in people of Northern European descent. 



These reports do not include variants in other genes linked to hereditary cancers and the absence of variants included in this report does not rule out the presence of other genetic variants that may impact cancer risk. These reports are for over-the-counter use by adults, and provide genetic information to inform discussions with a healthcare professional. The PGS test is not a substitute for visits to a healthcare professional for recommended screenings or appropriate follow-up. Results should be confirmed by an independent genetic test prescribed by your own healthcare provider before taking any medical action.&nbsp; For important information and limitations regarding genetic health risk reports, visit https://www.23andme.com/test-info.

An image of the three Cancer PRS reports displayed on a mobile phone.

23andMe Launches New Genetic Reports on Common Forms of Cancer

Researchers at Johns Hopkins Bloomberg School of Public Health, Harvard, the Broad Institute, the National Cancer Institute, and 23andMe have developed a method that significantly improves the performance of polygenic risk score models for people of non-European ancestry.



This new method holds promises that future clinical use of new polygenic models will be less likely to exacerbate health inequities.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="155" src="http://35.88.189.111/wp-content/uploads/2021/12/Polygenic-Risk-score-1024x155.png" alt="An illustration of polygenic risk score models
" class="wp-image-29420" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-1024x155.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-300x45.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-768x116.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-880x133.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score.png 1026w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



<h2 class="wp-block-heading" id="h-what-are-polygenic-risk-scores">What Are Polygenic Risk Scores?</h2>



Over the last several years, these kinds of risk models, also known as <a href="https://blog.23andme.com/articles/nilanjan-chatterjee">polygenic risk scores, or PRS</a>, have begun to offer up meaningful risk information on many diseases like <a href="https://www.23andme.com/brca/">breast cancer</a>, <a href="https://blog.23andme.com/articles/screening-for-t2d">type 2 diabetes</a>, or <a href="https://www.23andme.com/topics/health-predispositions/coronary-artery-disease/">heart disease.</a> But the performance of these models — which rely on very large genome wide association studies and are based on hundreds or thousands or even many thousands of variants to calculate risk — perform poorly for non-Europeans. That’s in part because of the lack of genetic research that includes data from non-Europeans.



Outlined in a paper published in the journal <a href="https://www.nature.com/articles/s41588-023-01501-z">Nature Genetics,</a> this new method addresses that problem, improving both the performance and training and building speed of these risk models. 



<h2 class="wp-block-heading" id="h-how-is-the-new-polygenic-risk-model-changing-the-game">How Is the New Polygenic Risk Model Changing the Game?</h2>



Dubbed CT-SLEB, this new approach substantially improved the performance of polygenic risk models in diverse populations, especially among people with African ancestry. And these CT-SLEB models can be modeled much faster than other polygenic risk modeling methods.



“At 23andMe, we are committed to providing health value to everyone. With this collaborative study, we helped improve a method to make polygenic risk models perform better for underrepresented populations so that everyone can have a better understanding of their future health,” said Jianan Zhan, a senior scientist with 23andMe’s Product R&amp;D. “There’s great potential for using these models in clinical care too, but to make that a reality we need to make sure they work for people of all ancestries.”



<h2 class="wp-block-heading" id="h-how-the-prs-model-works">How the PRS Model Works</h2>



The scientists used three distinct steps in their approach. First, they used something they called “clumping and thresholding.” This allowed them to select risk variants relevant to different populations — European, African, East Asian, South Asian and Latino. Then, they used a statistical method called “Empirical-Bayes.” This statistical method uses the risk averages from the whole dataset to adjust the risk averages of each specific population. Finally, the team applied a third layer that involved a machine learning approach. Calling it “super learning,” this machine learning approach adjusts and improves the predictive accuracy of the polygenic risk model.



They then compared their model to nine other modeling methods across <a href="https://www.23andme.com/dna-ancestry/">five different ancestry groups</a>. They did this to test the predictive value for seven complex traits using data from more than 3.7 million 23andMe customers who consented to participate in research. These research participants were also of different ancestries. The 3.7 million includes more than 413,000 Latinos, 117,000 African Americans, 96,000 people of East Asian descent, and another 26,000 people of South Asian descent.  



It proved to be much faster, highly scalable and one of the most powerful methods for generating risk predictions in non-European populations, particularly among African Americans.



<h2 class="wp-block-heading" id="h-what-you-need-to-know-about-polygenic-risk-scores">What You Need to Know About Polygenic Risk Scores</h2>



While this new approach offers promise, the study authors noted some of the limitations. This new method substantially improved the performance of polygenic risk models in many settings, but there is still room to improve results for non-Europeans. 



In addition, the authors noted that the best approach for risk prediction might involve using multiple methods and combining the results. Even with best methods, the disparity in polygenic risk model performance may remain. That is unless there are larger sample sizes from understudied populations.



<a href="https://www.23andme.com/dna-reports-list/">23andMe offers more than 30 reports</a> based on polygenic risk models. The model is trained with a different method but includes some of the approaches outlined in this paper that were adjusted to account for the uniqueness of our database. You can learn more about our<a href="https://permalinks.23andme.com/pdf/23_21-PRSMethodology_May2020.pdf"> methods for creating these polygenic scores</a>.



With its large size and scale, 23andMe offers a unique opportunity to develop and improve upon these types of models with unmatched power.

Understanding Polygenic Risk Scores (PRS)

The numbers are staggering.&nbsp;
In the last two decades, the number of Americans with <a href="https://www.23andme.com/topics/health-predispositions/type-2-diabetes/">Type 2 diabetes</a> has reached epidemic proportions. More<a href="https://www.cdc.gov/diabetes/basics/type2.html"> than a third</a> of adults in the United States are pre-diabetic. The vast majority of them, 84 percent, don&#8217;t even know they are at risk.&nbsp;
About 34 million people in the US have diabetes, and 20 percent don&#8217;t know it. Type 2 diabetes is the seventh leading cause of death in the United States. The costs for treating those with diabetes are estimated to be more than $327 billion annually, according to the<a href="https://www.diabetes.org/resources/statistics/cost-diabetes"> American Diabetes Association.</a>
<h6>Preventable</h6>
Delayed diagnosis for those who are pre-diabetic as well as those who have already developed type 2 diabetes, hampers effective treatment. According to the Centers for Disease Control, more than seven million people in the United States have undiagnosed diabetes. And more than 80 million&nbsp;are pre-diabetic and at risk.
This is all for a largely preventable condition.
Like a lot of different conditions, early diagnosis or more accurate predictors for risk could help those at the highest risk for type 2 diabetes. Right now, the process by which we screen for the risk of developing type 2 diabetes relies primarily on age, family history, and body mass index (BMI). But a recent study by researchers from 23andMe identified how we could improve that, offering hope to identify people sooner who have an increased likelihood of developing type 2 diabetes.
<h6>Improving Screening</h6>
The study, published in a special issue of the journal<a href="https://www.frontiersin.org/research-topics/23213/dna-based-population-screening-for-precision-public-health"> Frontiers in Genetics</a> found that adding genetics in the form of a polygenic risk model to family health history and BMI can substantially improve current screening for type 2 diabetes.
“Type 2 diabetes is an enormous public health issue affecting millions of people in the United States alone,” said Jeff Pollard, MD, 23andMe’s Director of Medical Affairs and a co-author of the study. “This paper shows that using a polygenic risk model for T2D adds information that is separate from family history, countering one major argument against the utility of using this kind of polygenic risk model in population screening.”
Not only does adding the polygenic risk model improve screening for those at risk for type 2 diabetes, but it would also identify slightly more individuals with type 2 diabetes who simply don’t yet know they have it. This offers opportunities for earlier treatment for those with the condition and prevention for those who have not yet developed type 2 diabetes.
<h6>Polygenic Scores</h6>
Over the last several years, scientists have developed so-called polygenic scores that rely on large sets of genetic and non-genetic data to better calculate disease risk. For this study 23andMe, researchers relied on data from more than 3.8 million 23andMe customers who consented to participate in research. Then our scientists combined results from several genome-wide association studies to identify more than 11,000 genetic variants associated with type 2 diabetes. From there, researchers built a model to assess the likelihood of developing the condition. 
The field of genetic prediction has relied mostly on data from participants of European descent, and the lack of global representation has often meant that polygenic scores developed in one population don&#8217;t work as well in others. In this study, however, 23andMe scientists were able to show that the PGS would help in screening practices in the Hispanic/Latino community as well.
Although 23andMe uses a polygenic risk score for its<a href="https://www.23andme.com/topics/health-predispositions/type-2-diabetes/"> Type 2 Diabetes Report (Powered by 23andMe research)</a>, it is not the same as the polygenic risk score used in this research. The T2D report calculates a polygenic score based on more than 1000 genetic variants, the research is based on a model that includes 11,999 variants. In addition, the report also relied on phenotypic data from more than 1.1 million 23andMe customers who consented to participate in research. While the research included phenotypic data from more than 1.6 million customers who consented to participate in research.

<hr>
Read more posts on type 2 diabetes and polygenic scores:
<ul>
<li><a href="https://blog.23andme.com/23andme-research/type-2-diabetes-data/">23andMe Data on the Genetics of Type 2 Diabetes</a></li>
<li><a href="https://blog.23andme.com/health-traits/spit-podcast-takes-on-type-2-diabetes/">Spit Podcast Takes on Type 2 Diabetes</a></li>
<li><a href="https://blog.23andme.com/health-traits/type-2-diabetes/">23andMe Offers New Genetic Report on Type 2 Diabetes</a></li>
</ul>

Improving Screening for Type 2 Diabetes

My Risk of Developing the “Disease of Kings.”

<figure class="wp-block-image alignright"><img loading="lazy" decoding="async" width="300" height="300" src="https://blog-api.23andme.com/wp-content/uploads/2017/03/sun-300x300.png" alt="" class="wp-image-25177" srcset="https://blogcms.23andme.com/wp-content/uploads/2017/03/sun-300x300.png 300w, https://blogcms.23andme.com/wp-content/uploads/2017/03/sun-150x150.png 150w, https://blogcms.23andme.com/wp-content/uploads/2017/03/sun-271x271.png 271w, https://blogcms.23andme.com/wp-content/uploads/2017/03/sun-372x372.png 372w, https://blogcms.23andme.com/wp-content/uploads/2017/03/sun-574x574.png 574w, https://blogcms.23andme.com/wp-content/uploads/2017/03/sun.png 600w" sizes="auto, (max-width: 300px) 100vw, 300px" /></figure>



A team of scientists at 23andMe created a new model to better estimate skin cancer risk, one of the most commonly diagnosed forms of cancer.



Details of the new model are included in a study published in <a href="https://www.nature.com/articles/s41467-020-20246-5">Nature Communications</a> today.



Using genetic and other data from more than 210,000 customers who consented to participate in the research, the 23andMe team created a model to calculate a risk score for the three forms of skin cancer. The model relied on more than 100 known genetic variants for skin cancers and dozens of non-genetic risk factors, including family cancer history, <a href="https://www.23andme.com/topics/traits/skin-pigmentation/">skin pigmentation</a>, and sun exposure.



According to the study&#8217;s lead author, Pierre Fontanillas, Ph.D., and a senior statistical geneticist at 23andMe, the new model could help detect skin cancer earlier. 



“There remains considerable room to improve the risk model by including additional data, especially from people of non-European ancestry,” said Pierre. “But we’ve shown the ability to use a risk model to potentially identify people with elevated risk for skin cancer who do not currently have identifiable symptoms.”<code></code><wp-block data-block="core/more"></wp-block>



<figure class="wp-block-image alignright wp-image-26632 size-medium"><img loading="lazy" decoding="async" width="199" height="300" src="https://blog-api.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-199x300.jpg" alt="" class="wp-image-26632" srcset="https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-199x300.jpg 199w, https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-768x1156.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-680x1024.jpg 680w, https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-585x880.jpg 585w, https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-784x1180.jpg 784w, https://blogcms.23andme.com/wp-content/uploads/2018/10/©Piter2016-23andMe-PierreFontanillas-033-copy-scaled.jpg 1701w" sizes="auto, (max-width: 199px) 100vw, 199px" /><figcaption class="wp-element-caption">23andMe Senior Statistical Geneticist Pierre Fontanillas, Ph.D.</figcaption></figure>



<h2 class="wp-block-heading" id="h-one-in-five">One in Five</h2>



Such early detection could have broad benefits. In the United States alone, one in five people is likely to develop skin cancer in their lifetime. Despite being preventable, more than 15,000 Americans die each year from one of the three major types of skin cancer — basal cell carcinoma, squamous cell carcinoma, and melanoma.



Using the new model they developed, the 23andMe scientists found the research participants in this study with the highest risk scores were up to 13 times more at risk of <a href="http://35.88.189.111/articles/new-23andme-report-on-skin-cancer">developing skin cancer.</a> The work doesn’t just offer the potential for identifying people with elevated risk for cancer. It also could help predict such things as the age of onset and the severity of cancer.



Early detection and treatment for skin cancer can go a long way in improving outcomes. Currently, early detection relies on regular full-body skin examinations. While inexpensive and non-invasive, there’s little evidence that it’s an effective method for detecting skin cancer in the general population. Developing a more accurate predictor for individual risk for cancer has been difficult.



<h2 class="wp-block-heading" id="h-new-tools">New Tools</h2>



Finding tools for better risk prediction and earlier detection offers hope for better outcomes.



“These scores rely on the long tail behavior of the genetic and non-genetic factors and potentially enable the identification of asymptomatic individuals with elevated skin cancer risk,” the scientists said in the paper.



Because this initial work included data primarily from customers with European ancestry, the researchers plan to expand the study to include data from individuals with non-European ancestry. Also, they hope to improve how they estimate sun exposure and refine the genetic risk score. According to the researchers, the goal is to develop risk estimates accurate enough to be used clinically and individually.



<h2 class="wp-block-heading" id="h-polygenic-risk-scores">Polygenic Risk Scores</h2>



Over the last several years, scientists have developed <a href="https://blog.23andme.com/articles/nilanjan-chatterjee">polygenic risk scores </a>that rely on large sets of genetic and non-genetic data to better calculate disease risk. 23andMe has used this kind of risk modeling for its <a href="https://www.23andme.com/topics/health-predispositions/type-2-diabetes/">Type 2 Diabetes Report (Powered by 23andMe research)</a>. The T2D report calculates a polygenic score based on more than 1000 genetic variants. The report also relied on data from more than 1.1 million 23andMe customers who consented to participate in the research. 



As more genetic data become available, polygenic risk models are increasingly being used to help calculate risk. Often, these models use many hundreds, or even thousands, of genetic variants to calculate risk. These new models can also include other factors — such as lifestyle and environmental influences — to offer a clearer picture of disease risk. Also, including data from more diverse populations can be used to predict risk in underrepresented populations better.



At this time, 23andMe does not offer a report on skin cancer.

A Better Way to Estimate Skin Cancer Risk

This week, 23andMe is hosting its third annual Genome Research Day, a meeting focused on human genomics research happening in and around the Bay Area. This event will also allow 23andMe scientists to explain some of our latest research. <img loading="lazy" decoding="async" class="wp-image-27142 size-full alignright" src="http://35.88.189.111/wp-content/uploads/2019/06/nilanjan_orig.png" alt="" width="350" height="329" srcset="https://blogcms.23andme.com/wp-content/uploads/2019/06/nilanjan_orig.png 350w, https://blogcms.23andme.com/wp-content/uploads/2019/06/nilanjan_orig-300x282.png 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Among the many presentations, we’ll highlight some of our work around polygenic risk modeling. We asked Johns Hopkins University statistical geneticist Nilanjan Chatterjee, Ph.D., a Bloomberg Distinguished Professor of Biostatistics and Medicine at Johns Hopkins University, to help us put into context the work being done around the world on risk modeling. 
Chatterjee is a noted expert in developing risk prediction models, particularly around cancer. As more genetic data becomes available, polygenic risk models are increasingly being used to help calculate the cumulative risk of not just a few genetic variants but the many hundreds or even thousands of variants that convey risk. In addition, these new models can also include other factors  — such as lifestyle and environmental influences — to offer a clearer picture of disease risk.
<h2>Bigger and Getter GWAS</h2>
Thank you for chatting with us, Dr. Chatterjee. Can we start by asking why we are hearing so much about polygenic risk scores now, even though they have been around for a while? 
Dr. Nilanjan Chatterjee: My guess is that because the sample size for genome-wide association studies has increased by leaps and bounds, this has led to much more improvement (polygenic risk scores). In particular, PRS is now providing meaningful risk-stratification for several common diseases like breast cancer, type-2 diabetes, and heart disease. I anticipate the power of (these models) for risk-stratification will continue to increase as the sample size for GWAS grows, especially for non-European ethnic groups where the data have been lacking in the past.
There are many different kinds of non-genetic risk models to estimate risk. How are polygenic risk score models different, and is that important?
Dr. Chatterjee: Well, that is an interesting question that does not have a simple answer. At one level, all models are trying to produce an estimate of &#8220;risk,&#8221; which is a single number. It does not matter whether this is being driven by genetic or non-genetic factors as long as the overall model performs well. But at another level there are important pros- and cons- for using genetic and non-genetic factors. It can be simpler for people to feed in information on simple factors like BMI, smoking history, and family history through filling out questionnaires. While one-day, genetic information, including PRS, may be part of routine clinical care, we are not there yet.
On the other hand, lifestyle factors and other non-genetic factors, including various biomarkers, change over time, and they may have limited value for long-term risk prediction based on a single measurement. Information on inherited DNA needs to be collected only once in a lifetime. We often see that genetic predisposition leads to risks that remain throughout an individual’s lifetime, and non-genetic risk factors act in a multiplicative fashion on the background of that stable genetic risk.
Complicating the future use of polygenic risk models is a huge issue related to our confidence in the systems in place to protect the security of our genetic information. But setting aside the confidentiality issue, I feel future risk models should include both genetic and non-genetic information. It’s important to understand risks associated with lifestyle because that is something we can do something about it. At the same time, genetics is an important determinant of our background risk, and even if it cannot or should not be modified, it can help us make decisions regarding strategies for risk reduction through lifestyle changes, medication, and screening.
<h2>Non-Genetic Factors</h2>
We focus a lot on how polygenic risk scores can include many more genetic variants associated with risk. Still, they can be extended to also use non-genetic variables and environmental factors. What is the significance of this, and do you see some good examples of risk modeling that include these different types of data?
Dr. Chatterjee: Coronary heart disease and breast cancer are two fields that have historically been ahead in the development and validation of risk models for clinical application. In both fields, I see considerable effort going toward the integration of polygenic risk scores with other types of information, such as rare, high-penetrant mutations and non-genetic risk factors. 
For example, the BOADICEA model that uses extensive family history information to predict the risk of breast cancer has recently been extended to include polygenic risk scores and non-genetic risk factors (Lee et al., Genetics in Medicine, 2019). In our own work, we have recently put a lot of effort into integrating polygenic risk scores for breast cancer (Mavaddat et al. AJHG, 2019) with information on a set of classic risk factors for breast cancer. We’ve validated these models across a variety of cohorts encompassing 6 different countries (ongoing work).
How far are we from incorporating polygenic risk scores into day-to-day health care?
Dr. Chatterjee: We still have a while — perhaps 10 years —  to sort a few things out before polygenic risk scores can become part of routine care. There are a lot of questions we need to address. First, how much will it cost, and who will pay for it? Beyond the costs, what kind of data do we need to convince insurance companies and employers of the value of polygenic risk scores in healthcare? Also, how do we reassure the public that the information will not be misused? Finally, how will the information be communicated so that it does not create either a sense of false alarm or reassurance? These are just a few thoughts that come to my mind.
<h2>Actionable?</h2>
Do you think these risk models offer people actionable information in the current state?
Dr. Chatterjee: Yes, I do think some well-validated models could generate useful information now to guide preventive action. That said, given the current popularity of PRS and risk models in general, I am also wary that many risk models out there are not correctly validated and could generate misinformation.
What are your thoughts about 23andMe’s use of polygenic scores for Type 2 Diabetes?
Dr. Chatterjee: I am somewhat familiar with 23andMe’s Type-2 diabetes report. The underlying methodology used is sound, and the data, as well as other data, shows that a PRS for type-2 diabetes can provide meaningful risk stratification for individuals, especially given that it&#8217;s a relatively common outcome. In the future, more effort is needed to improve the performance of PRS using additional GWAS studies, specifically for non-European populations. 
What are some strategies for including more data from non-Europeans to make polygenic risk models more broadly applicable?
Dr. Chatterjee: Well, of course, we need more GWAS for non-European populations. Nevertheless, in most cases, complex diseases have many shared genetic backgrounds across different ethnic populations. So, we should do everything possible to exploit available data across multiple ethnic groups to develop polygenic risk scores optimized for other ethnic populations. More research is needed to develop methodologies in this area. 
Dr. Nilanjan Chatterjee, Ph. D., is a Bloomberg Distinguished Professor of Biostatistics and Medicine at Johns Hopkins University. Dr. Chatterjee’s opinions expressed here are his own and not those of Johns Hopkins University. In addition, 23andMe has not compensated him for his participation in this interview, and he has no other financial interest in 23andMe.

PRS — Page 2