By Eloycsia Ratliff, MPH, 23andMe Medical Education Project Manager
We know that diet and exercise play an important role in a person&#8217;s likelihood of developing <a href="http://www.23andme.com/topics/health-predispositions/type-2-diabetes/">type 2 diabetes</a>, but what role does genetics play?<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-199x300.jpg" alt="" class="alignright size-medium wp-image-27136" width="199" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-199x300.jpg 199w, https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-768x1156.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-680x1024.jpg 680w, https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-585x880.jpg 585w, https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-784x1180.jpg 784w, https://blogcms.23andme.com/wp-content/uploads/2019/06/©Piter2016-23andMe-MichaelMulthaup-022-scaled.jpg 1701w" sizes="auto, (max-width: 199px) 100vw, 199px" />
That’s a question 23andMe researchers have been investigating, and at a meeting of the American Diabetes Associations (ADA) Annual Conference on June 10th in San Francisco, 23andMe’s Senior Product Scientist, Michael Multhaup, Ph.D., will be presenting some of what we’ve learned in a presentation titled “Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database.” 
<h6>Polygenic Score</h6>
Dr. Multhaup’s presentation comes on the heels of the release of 23andMe’s Type 2 Diabetes report (T2D)*  that is currently available to eligible customers who have opted into receiving health reports. The T2D report calculates a polygenic score based on more than 1000 genetic variants. A polygenic score quantifies how an individual’s genetics may contribute to developing a complex disease, such as T2D. For the T2D genetic susceptibility study, 23andMe researchers generated a polygenic score based on more than 1200 variants discovered using data shared by more than 600,000 consented research participants who self-reported if they had been diagnosed with T2D.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2019/03/T2D-Image-300x138.jpg" alt="" class="alignright size-medium wp-image-26911" width="300" height="138" srcset="https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-300x138.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-768x354.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-1024x473.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-880x406.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-1180x545.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image.jpg 1950w" sizes="auto, (max-width: 300px) 100vw, 300px" /> 
Our researchers then tested the performance of the polygenic score in separate sets of participants to cover five different ancestries — African-American, East-Asian, European, Latino and South Asian. Based on the results, 23andMe researchers were able to make associations between an individual’s genetics and their likelihood of developing T2D. Researchers categorized results into “increased likelihood” and “typical likelihood,” where an “increased likelihood” result means the likelihood of developing T2D from genetics alone exceeds the likelihood of developing the condition due to being overweight. 
<h6>Presentation of Findings</h6>
At the conference, Dr. Multhaup will present findings from this study and he will discuss the use of genetics as a screening tool to inform cost-effective interventions that could be used by both healthcare providers and their patients.
In addition to Dr. Multhaup’s scientific session presentation, 23andMe will host a booth in the exhibit hall (booth #1340) to engage directly with healthcare professionals over the three day conference from June 8th to June 10th. At the meeting, 23andMe plans to discuss with healthcare providers the impact of 23andMe’s health predisposition reports, such as theType 2 Diabetes report, on medicine and routine patient care. It is important for healthcare providers to understand the consumer experience and motivations, as well as available tools and resources, so they are prepared for patient encounters around direct-to-consumer genetic testing.
23andMe believes knowledge about genetic information has a role in improving health outcomes. Our goal in providing consumers with access to their genetic information is to provide insights into their likelihood of developing a condition, like T2D, before they develop that condition. Early access to this information has the potential to motivate individuals to be more proactive in changing health behaviors — a goal 23andMe wants for their consumers.
If you are attending the ADA conference in San Francisco and would like to learn more about the findings from 23andMe’s T2D research study, come to Dr. Multhaup’s presentation at Scientific Session 304-OR, Monday, June 10th 2:30 – 2:45pm. Also, look for us on the exhibition floor at booth #1340!
To stay up to date on health report releases and resources available to healthcare professionals, visit our 23andMe for healthcare professionals site at  <a href="https://medical.23andme.com/">https://medical.23andme.com/</a>.
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*The 23andMe Type 2 Diabetes report is based on 23andMe research and incorporates more than 1,000 genetic variants to provide information on the likelihood of developing type 2 diabetes.  The report does not account for lifestyle or family history and has not been reviewed by the US Food and Drug Administration. Visit <a href="http://www.23andme.com/topics/health-predispositions/type-2-diabetes">23andMe’s Type 2 Diabetes landing page</a> for additional important information.
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Eloycsia Ratliff

23andMe Data on the Genetics of Type 2 Diabetes

23andMe’s new Type 2 Diabetes report* offers customers insight into their likelihood of developing one of the most prevalent, pernicious, and yet preventable health conditions in the United States.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2019/03/T2D-Image-300x138.jpg" alt="" class="alignright wp-image-26911" title="diet and exercise can help lower risk of type 2 diabetes" width="350" height="162" srcset="https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-300x138.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-768x354.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-1024x473.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-880x406.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image-1180x545.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2019/03/T2D-Image.jpg 1950w" sizes="auto, (max-width: 350px) 100vw, 350px" />
This new report will impact more 23andMe customers than any other <a href="https://www.23andme.com/dna-health-ancestry">Health Predisposition report</a> the company has ever released. In part, this is because the likelihood of developing <a href="https://www.23andme.com/topics/health-predispositions/type-2-diabetes/">type 2 diabetes</a> is so high in the general population.
“Diabetes is a significant health issue in the United States that is expected to impact nearly half of the population,&#8221; said Anne Wojcicki, CEO and Co-Founder of 23andMe. &#8220;When customers learn about their genetic likelihood of developing type 2 diabetes, we believe there is an opportunity to motivate them to change their lifestyle and ultimately to help them prevent the disease.&#8221; 
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<h6>What’s a Polygenic Score?</h6>
The genes we inherit from our mother and father influence our risk of disease. While that’s pretty straightforward, the role genetics plays is a bit more complicated.
Although there are examples of a single genetic variant in a single gene causing certain conditions, it is often the case that hundreds or even thousands of variants — along with lifestyle and environmental factors — all play a role. And that’s precisely the case with type 2 diabetes.
For 23andMe’s new Type 2 Diabetes report, we created a model that incorporates more than 1,000 genetic variants to calculate a polygenic score for a customer’s likelihood of developing type 2 diabetes.
It’s not the first time we’ve used this method. However, it is the first time we’ve used this kind of polygenic score for a Health Predisposition report. In the past, we’ve used this method to develop our<a href="https://blog.23andme.com/health-traits/23andme-releases-first-of-its-kind-genetic-weight-report/"> Genetic Weight Report</a>. That report used both genetic data — hundreds of variants associated with BMI — and non-genetic data to calculate a person’s genetic predisposition to weigh more or less than average. 
<h6>Modeled Reports</h6>
Several other trait reports similarly rely on polygenic scores. For example, 23andMe’s recent reports on<a href="https://blog.23andme.com/health-traits/feeling-woozy-over-23andmes-new-report-on-motion-sickness/"> Motion Sickness</a>, the ability to<a href="https://blog.23andme.com/health-traits/itching-to-see-23andmes-new-trait-reports/"> Match a Musical Pitch</a>, and estimated<a href="https://blog.23andme.com/health-traits/23andme-adds-four-new-trait-reports/"> Wake Up Time</a> each use hundreds of variants to calculate one’s predisposition toward those traits.
23andMe will continue to use these kinds of polygenic modeled reports to report health predispositions to its customers. We are uniquely positioned to do this because of the data our customers contribute. This in turn allows our researchers to better understand the complex genetic underpinnings of various diseases. We can also then create polygenic models that take into account the cumulative effects of a large number of genetic variants. This allows us to give better estimates of their influence on different health conditions and diseases. 
You can learn more about how others are incorporating polygenic modeling to estimate risk by looking at coverage in the <a href="https://news.harvard.edu/gazette/story/2018/08/polygenic-risk-scoring-flags-likelihood-of-developing-common-diseases/">Harvard Gazette</a>. That article focuses on  research done by scientists at the Broad Institute of MIT, Harvard, and Massachusetts General Hospital. In the summer of 2018 the team published their findings in the journal <a href="https://www.nature.com/articles/s41588-018-0183-z?_ga=2.116551877.2133794146.1551300156-1054250013.1551300156#Abs1">Nature</a>. The study showed how they created a polygenic model to better estimate for the risk of five different conditions. The conditions included type 2 diabetes, breast cancer, and coronary artery disease.
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<h6>Rising Rates of Diabetes</h6>
In the United States alone a staggering one in three Americans have prediabetes, according to estimates from<a href="https://www.cdc.gov/nchs/products/databriefs/db319.htm?utm_source=STAT+Newsletters&#038;utm_campaign=ae2c97fb19-MR_COPY_12&#038;utm_medium=email&#038;utm_term=0_8cab1d7961-ae2c97fb19-150868577"> the U.S. Centers for Disease Control and Prevention</a>. Worse, 90 percent don’t know they have it. The impact is even greater among certain ethnicities. For example, Hispanics have the highest rates of diabetes with about 20 percent having the condition.
Worldwide, as lifestyle and diets are changing, the prevalence is also increasing. Beyond the very real human costs are the healthcare costs for treating the condition.  In the United States estimates for the costs of treating diabetes are more than $327 billion per year, according to the American Diabetes Association.
Despite the alarming statistics, there’s reason to be optimistic. Type 2 diabetes is one condition that can be prevented or delayed with lifestyle and diet changes. Genetics, family history, ethnicity, and age all contribute to the likelihood for developing type 2 diabetes. But type 2 diabetes is preventable. In many cases the likelihood can be lessened with a healthier diet and exercise. That’s where this report could help, by raising awareness among customers about their likelihood of developing the condition. There is some evidence that people do make positive changes to their diet and exercise more after getting genetic testing, according to<a href="http://www.genomes2people.org/wp-content/uploads/2018/07/20170502_PGen_BMCMedicalGenomics_Nielsen_DietExerciseDTC.pdf"> 2017 study</a> led by<a href="http://www.genomes2people.org/about/"> researchers</a> at Brigham and Women’s Hospital, Broad Institute and Harvard Medical School.
<h6>The New Report and the Genetics of Type 2 Diabetes </h6>
We hope that 23andMe’s new Type 2 Diabetes report will raise awareness about diabetes. The report also informs customers of the potential of making healthy lifestyle changes to lower one’s likelihood of developing type 2 diabetes. We’re excited by the potential that this report has for making a difference in people’s lives, but it’s significant for another reason as well.
This report is built using real-world data from more than 2.5 million 23andMe customers who have opted into research. Some of those customers have the condition and others do not. Together the data from those cusomters have allowed our product scientists to create what’s called a polygenic score. To asses an individuals likelihood of developing type 2 diabetes, our team created a model that takes into account more than a thousand genetic variants.
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<h6>Polygenic Score</h6>
Research has shown that type 2 diabetes is partially impacted by many genetics. Many genetic variants  each individually have a tiny impact on the likelihood of developing it. The Type 2 Diabetes report calculates the combined effects of more than 1,000 of these variants. These variants, known as single nucleotide polymorphisms ( SNPs)  are variations in DNA sequence at particular locations in the genome. The calculation uses all these variants to arrive at a polygenic score.  The report can help customers learn how their genetics, influence the likelihood of developing type 2 diabetes. It also looks at other factors such as  weight, age and lifestyle. In addition, the report also suggests actions customers can take to lower that likelihood.
Unlike other 23andMe health reports we developed and validated the Type 2 Diabetes report  completely on 23andMe research data. The report also underwent scientific review by our team of scientists, as well as reviews by our Medical Affairs and Regulatory teams. In addition, to create this report 23andMe relied on the expertise and knowledge of external experts. We included input from other scientific and medical professionals who are familiar with polygenic scores and the condition itself.
To learn more about the science behind 23andMe’s new Type 2 Diabetes report see <a href="https://permalinks.23andme.com/pdf/23_19-Type2Diabetes_March2019.pdf">our white paper</a>.
*Note: The 23andMe Type 2 Diabetes report is based on 23andMe research and incorporates more than 1,000 genetic variants to provide information on the likelihood of developing type 2 diabetes.  The report does not account for lifestyle or family history and has not been reviewed by the US Food and Drug Administration. Visit www.23andme.com/topics/health-predispositions/type-2-diabetes for additional important information.
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23andMe Blog

23andMe Blog Team

23andMe Offers New Genetic Report on Type 2 Diabetes

A new study found that many common genetic variants together explain why migraines cluster in some families.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2013/09/Migraine-Photo-200x300.jpg" alt="" class="alignright wp-image-19308 size-medium" title="migraines" width="200" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2013/09/Migraine-Photo-200x300.jpg 200w, https://blogcms.23andme.com/wp-content/uploads/2013/09/Migraine-Photo.jpg 566w" sizes="auto, (max-width: 200px) 100vw, 200px" />
The <a href="https://www.cell.com/neuron/fulltext/S0896-6273(18)30322-2">study</a>, lead by scientists from Massachusetts General Hospital, Harvard Medical School, the Broad Institute and the University of Helsinki, investigated three subtypes of migraines. Researchers used data from about 1,500 Finnish families. 
It is the largest ever study of families with migraine. 23andMe was one of more than a dozen institutions that contributed to this study. 
“Both rare, high-impact and common genetic variants with smaller impact could contribute to the familial aggregation of migraine,” said Padhraig Gormley, Ph.D, a lead author of the study who works at the Broad Institute. “In this study, we wanted to find out which one is more important and whether the genetic load is higher in certain types of migraine.”
<h6>Migraine Subtypes</h6>
Migraines — the severe recurring headaches that may include symptoms such as nausea and light sensitivity — are fairly common. They affect an estimated 20 percent of the population. About a third of those with migraines experience additional neurological symptoms, referred to as aura. These often occur just before or during a migraine. 
Researchers looked at whether there were different genetic mechanisms involved in two subtypes of migraines with aura. The two of subtypes were migraines with typical visual aura, and the less common subtype, hemiplegic migraines, which are accompanied by a motor weakness aura. Scientists had previously identified genetic variants associated with this common brain disorder. But there is still much to learn about the underlying biology. One lingering question is why the condition clusters in families, and that’s what this study focused on.
Two years ago this same consortium of scientists conducted what was at that time the largest genome-wide association<a href="https://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3598.html"> study</a> of migraines ever done. That study found more than 40 genetic variants associated with the condition.
<h6>Polygenic Score </h6>
For this most recent study, the researchers wanted to determine if rare variants or a combination of rare and common variants could explain why migraines cluster in some families. As in the last study, this one relied in part on a meta-analysis of data gathered together from 22 different genome-wide association studies. Together this included data from more than 375,000 people, and about 170,000 of those individuals are 23andMe customers who consented to participate in research.
By using this data, the researchers were able to create something called a “polygenic risk score,” gathering together all the variants that contributed to risk for migraines identified in these studies. This model was then used in studying a smaller cohort of Finnish families with migraines. 
<h6>Risk in Families</h6>
The scientists were interested in seeing if there was a difference in comparing the genetic risk within families to risk for migraines in the general population, as well as looking to see if these differences could be explained by the accumulation of common variants or the contribution of a few rare variants. They were particularly interested in looking at hemiplegic aura migraines, which were thought to be caused by rare genetic variants in three genes.
But what the researchers found across the board was that the combined effect of common variants was greater than the effect of any rare variants.
“Our study supports the hypothesis that migraine subtypes are genetically heterogeneous diseases, and that common polygenic variation significantly contributes to the aggregation of the disease in families, both for common and rare migraine subtypes”, said Aarno Palotie, Ph.D, another study author who works at the University of Helsinki.
The study was conducted in collaboration with members of the<a href="http://www.headachegenetics.org/"> International Headache Genetics Consortium</a> and the 23andMe <a href="https://research.23andme.com/research/">Research Team</a>.
Read more on the study in the publication <a href="https://www.cell.com/neuron/pdfExtended/S0896-6273(18)30322-2">Cell</a>.

Largest-ever family study of migraines provides new insight into the disease

23andMe scientists will be at the annual American Society of <img loading="lazy" decoding="async" class="alignright size-full wp-image-24281" src="https://blog-api.23andme.com/wp-content/uploads/2016/09/microscope.jpg" alt="microscope" width="131" height="166" />Human Genetics meeting in Vancouver this month, sharing a wide spectrum of interesting data, including more on the genetics of Parkinson’s disease, promising new methods for drug discovery, and even some fun findings around traits like nail biting and the ability to carry a tune.
These conferences, which attract thousands of geneticists and include hundreds of scientific presentations over four days, are tough to encapsulate in one article. But each year, ASHG does a good job of keying in on the most interesting current issues in the field of genetics, creating forums for some of those big ideas, and then offering scientists a chance to show off their latest work in those areas.
This year is no different, with talks on gene editing, strategies for incorporating health records into genetic research, and panel discussions on the genetics of cancer and aging.
<h2>Therapeutics</h2>
Along with presenting some of our findings, 23andMe also has the honor of having two of our scientists speak at this year’s conference.
Richard Scheller, 23andMe’s chief science officer and head of the therapeutics group, will speak on Wednesday during a session on using genome-wide association studies to help develop drug targets. Richard will be one of four speakers during a session titled “From GWAS and Mendelian Genes to Therapeutic Drug Targets.” 23andMe’s therapeutics group is using human genetic data as the starting point for identifying new therapies for both common and rare diseases.
<h2>Associations with Nail Biting</h2>
23andMe senior statistical geneticist Chao Tian will also speak at the four-day conference. Chao is no stranger to the conference, having<a href="https://blog-api.23andme.com/wp-content/uploads/2013/10/GWAS-for-Susceptibility-to-Infection.pdf"> presented a poster in 2013</a> that used genome-wide association studies to classify HLA alleles associated with infectious diseases. This year, Chao will speak in a short “platform session” on Saturday, Oct. 22, focused on Neuropsychiatric Disease in the Young and Old. She will present data on genetic and phenotypic associations for<a href="https://ep70.eventpilot.us/web/page.php?page=IntHtml&amp;project=ASHG16&amp;id=160121314"> nail biting</a>. Among her findings were that some of the variants associated with the trait are in genes or gene regions that have also been associated with certain psychiatric disorders.
Along with talks, panel discussions, and plenary sessions, scientists will also highlight their findings in poster sessions – which usually consist of vast halls where researchers literally post their work on boards and stand by to answer questions posed by anyone who happens to walk by. This informal question and answer session – involving attendees, most of whom are scientists – can be the most stimulating part of the conference, where researchers are sometimes forced to explain their methods and defend their findings in real time.
Below is the list of some poster presentations 23andMe will present at ASHG. We’ll provide more details during the conference.
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<h2 style="text-align: center;">23andMe&#8217;s Presentations at ASHG</h2>
• Genetic variation underlying self-reported weight-loss success in the presence of a dietary intervention – Authors: J.F. Shelton; N.A Furlotte; R. Smith; C. Wheldon; M.N. Johnson; C. Wilson; G. Benton; R. Gentleman
• Interrogating gene-by-environment interactions using genetic risk scores – Authors: Furlotte; V. Vacic; G. Benton; A. Auton; D. Hinds
• Generalized polygenic risk prediction for direct-to- consumer genetic testing of non-medical traits – Authors: M.L. Multhaup; R.P. Smith; D. Hinds; N.A. Furlotte
• GWASs of ability to carry a musical tune and mathematical educational attainment – Authors: R. Bell; D. Hinds; C. Tian
• GWAS of levodopa-induced dyskinesia in Parkinson’s disease – Authors: O.V. Sazonova; I. HallgrÃ­msdÃ³ttir; J. Shelton; P. Cannon
• Phenome-wide association study of 28 variants associated with Parkinson’s disease in a web-based cohort – Authors: K. Heilbron; B. Alipanahi; P. Cannon
• Leveraging PheWAS to Fine Map Complex Trait GWAS Loci – Authors: F. Sathirapongsasuti; P. Fontanillas; V. Vacic; A. Auton
• Efficient calculation of genetic correlations across 700,000 pairs of diverse phenotypes – Authors: A. Kleinman; N. Furlotte; A. Auton; D. Hinds
• The impact of personal experience with direct ­-to- ­consumer genetic testing on physician readiness – Authors: E.S. Gordon; E. Kim; J. Cintron; R. Gold; J. Pollard; E. Nelson
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PRS — Page 3

23andMe Data on the Genetics of Type 2 Diabetes

23andMe Offers New Genetic Report on Type 2 Diabetes

Largest-ever family study of migraines provides new insight into the disease

23andMe Scientists To Present New Findings at ASHG

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