A massive new study, the largest genome-wide association study ever done, has found nearly all the common genetic variants that explain the heritability of height among people of European ancestry, and in the process may have set the framework for future genetic research into other traits and diseases.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/04/tallshadow-225x300.jpg" alt="" width="225" height="300" class="alignright size-medium wp-image-180" srcset="https://blogcms.23andme.com/wp-content/uploads/2008/04/tallshadow-225x300.jpg 225w, https://blogcms.23andme.com/wp-content/uploads/2008/04/tallshadow.jpg 300w" sizes="auto, (max-width: 225px) 100vw, 225px" />
Using data from about 5.4 million individuals, almost half of whom were 23andMe customers who consented to participate in research, the study identified 12,111 variants or single nucleotide polymorphisms (SNPs) that help explain differences in height.
“We feel that this is really a milestone,” said&nbsp;<a href="https://www.broadinstitute.org/node/7053">Joel Hirschhorn</a>, senior author on the study, an institute member at the Broad, and also a professor of genetics and Concordia Professor of Pediatrics at Boston Children’s Hospital and Harvard Medical School. “We’d been studying height for a while but had only identified a small fraction of common variant heritability. We’re now basically done mapping this heritability to specific genomic regions, and that highlights what increasing sample size can tell us about traits controlled by multiple genes.”
<h6>GIANT</h6>
Published in the journal <a href="https://www.nature.com/articles/s41586-022-05275-y">Nature</a>, the study, led by researchers at the <a href="https://www.broadinstitute.org/news/largest-genome-wide-association-study-ever-uncovers-nearly-all-genetic-variants-linked-height">Broad Institute</a> and the international <a href="https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium">Genetic Investigation of ANthropometric Traits (GIANT) Consortium</a>, is the culmination of a multi-year effort to foster collaboration between academic, non-profit, government, and commercial partners. In their effort, the researchers collected, merged, and analyzed numerous independently generated genome-wide association studies into a single data set. In all, there are more than 200 different datasets incorporated into this study, which included contributions from hundreds of scientists from around the world.
<h6>The Power of Scale</h6>
What they found is important not just because of what it says about height, syndromes, and abnormalities affecting stature, but what it says about the potential of using very, very large amounts of data to generate insights into the genetics of different traits and conditions. Because height is so heritable, and because it is easy to measure someone’s height, it offers a very straightforward way to conduct a genetic study into a trait.
&#8220;This study highlights the ability of large-scale genetic studies to reveal the underlying biology of human phenotypes,” said Adam Auton, 23andMe’s Vice President of Human Genetics. 23andMe was one of a long list of institutions and organizations involved in the study.
“With this 5.4 million person study, we&#8217;re now at the stage where we&#8217;re starting to saturate our genetic understanding of height,” Auton said. “However, for other phenotypes — particularly human diseases — we&#8217;re a long way from saturation, and there is a lot we don&#8217;t yet understand.&#8221;
<h6>Heritability of Height</h6>
Heritability is the measure of how much our DNA explains the differences in specific traits or conditions. A SNP is a one-letter variation in the genetic code at a single point along the genome. These common variants are associated with differences in everything from traits like the color of our eyes or our height, or our risk for certain diseases.
Along with genetics, one’s environment — diet, for instance — also plays a role in these different traits and conditions. In the case of height, genetics has an outsized role in explaining about 80 percent of the variation. Because researchers included more than twice the number of individuals in this study from the next largest height study, they were able to discern almost all the heritability for height. So, size matters in genetic studies.
Previous height studies were large but just not large enough. According to the authors, this study was big enough to discern almost all of the heritability for height. In finding most of the variants that explain the heritability for height, the authors estimate that they’ve now identified variants that account for 40 percent of all variation in height in people with European ancestry. But they’ve identified only around 10–20 percent of the variation in people of other ancestries.
<h6>Diversity Matters</h6>
Also significant is that the study found that the genetic variants associated with height clustered within or near genes or gene regions associated with growth and development. That makes sense, but scientists were not so sure that is what they’d find. Many scientists thought that perhaps the variants they’ve identified could be found randomly sprinkled throughout the genome. But seeing that there is clustering will allow researchers to focus more on the clues around the biology and processes involved in individual traits like height.
In addition, the study illustrates something we already know about genetic research: diversity matters.&nbsp;
Although there were large numbers of individuals – more than a million – with African, Asian, and Latino ancestry included in this study, the vast majority of the data came from people of European ancestry. Some of the variants associated with height were associated with individuals of all different ancestries, but the findings were most applicable to those of European ancestry.&nbsp;
The researchers concluded that their study would benefit from data from a more diverse pool of individuals, especially those of African ancestry since people of African ancestry have the most genetic diversity of all populations. Not only would it improve the predictive power of the models developed to predict height for non-Europeans,&nbsp; it would also help in identifying causal genes and rare variants involved in height.
Read the full paper <a href="https://www.nature.com/articles/s41586-022-05275-y">here</a>.
&nbsp;

23andMe Blog

23andMe Blog Team

Giant Study Offers Insights into the Genetics of Height

A <a href="https://www.nature.com/articles/s41598-022-18703-w">new study</a> found that the genetic variants that underlie the ability to move to the beat of music also predict other measures of musicality, including one’s ability to follow a melody, distinguish pitch or rhythm, or even the amount of time practice singing or playing an instrument.&nbsp;
Researchers at the Max Planck Institute of Empirical Aesthetics and 23andMe used results from a recent<a href="https://blog.23andme.com/23andme-research/we-got-the-beat/"> genome-wide association study</a> (GWAS) on beat synchronization to estimate an individual’s genetic musical propensity using a polygenic score (PGS) approach in a large sample of 5,648 Swedish twins.&nbsp;
In addition to providing their genetic information, the twins were asked to complete various music questionnaires and music-related tasks.&nbsp;
Control phenotypes included non-musical traits and achievements like general intelligence, sports practice, and global and work-related flow experiences.&nbsp;
<h6>Genes and Environment Working Together&nbsp;</h6>
The team found that the PGS of self-reported beat synchronization ability (referred to in the study as PGSrhythm) was able to predict overall musicality – including musical skills as well as a tendency to enjoy and engage in musical behavior – but had no impact on the control phenotypes that were not directly related to music.
They also identified a relationship between a musically enriched childhood environment and an individual’s PGSrhythm, suggesting a correlation between genes and environment. This means that an individual&#8217;s environmental exposure (for example, whether they will take music classes) can depend on their genetic predisposition to music.
Beyond furthering the understanding of musicality’s genetic architecture, this work has far-reaching implications for the validity of using a polygenic score approach in future genetic research and shows that even a minimal phenotype used in the discovery GWAS can be a relatively good indicator of broader musicality.&nbsp;
Find out more <a href="https://www.vumc.org/music-cognition-lab/news/faq-about-beat-synchronization-gwas-study">here</a>.&nbsp;

What the Polygenic Basis of Rhythm Can Tell Us About Musical Traits

A new study by researchers at the Harvard T.H. Chan School of Public Health confirms<a href="https://blog.23andme.com/23andme-research/anxiety-depression-long-covid/"> findings from 23andMe</a> that depression and anxiety dramatically increase the likelihood of experiencing long COVID.
Published online in JAMA Psychiatry earlier this month, the<a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796097"> study</a> found that psychological distress in the form of depression, anxiety, stress, and loneliness were more predictive than many physical risk factors like obesity, asthma, and hypertension, said Siwen Wang, the researcher in the Department of Nutrition at Harvard T.H. Chan School who led the study.
“We were surprised by how strongly psychological distress before a COVID-19 infection was associated with an increased risk of long COVID,”<a href="https://www.hsph.harvard.edu/news/press-releases/psychological-distress-before-covid-19-infection-increases-risk-of-long-covid/"> Siwen said.</a>
<h2>Psychological Stress Increases Risk of COVID</h2>
The team’s findings showed that psychological stress contributed to a one-and-a-half-fold increase in the risk for long COVID. 23andMe’s results showed a two-fold increase. But the differences in the two studies may be explained by how the studies defined long COVID. 23andMe looked at data from individuals with a formal diagnosis of long COVID. The Harvard study didn&#8217;t just look those with a diagnosis but with COVID symptoms lasting four weeks or longer. But when applying similar criteria to the 23andMe data, our researchers also saw a one-and-a-half-fold increased risk of developing long COVID.
The Harvard study examined data from 54,000 individuals over a 19-month  period. About 3,200 of participants in the study contracted COVID. The 23andMe study included data from more than 100,000 individuals who reported contracting COVID-19. Of those, more than 26,000 reported that they had experienced long COVID. Over 7,000 of participants said they’d been diagnosed with it. Even after a year, more than 10 percent of those in 23andMe’s study  continued to have symptoms like brain fog, fatigue, and shortness of breath. It’s important to note that long COVID refers to individuals with symptoms that linger weeks, months, or longer after a COVID-19 infection.
<h2>23andMe Long COVID Findings</h2>
Data from 23andMe’s as-yet unpublished study<a href="https://blog.23andme.com/23andme-research/anxiety-depression-long-covid/"> first appeared on our blog. </a>It is part of<a href="https://blog.23andme.com/tag/covid-19/"> a series of studies</a> being conducted by 23andMe scientists since the beginning of the pandemic in 2020.
Among the areas of study is research on<a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/"> the role blood type plays</a> in severity and susceptibility to the virus. Our researchers have also drawn new insights into the genetics that influence<a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/"> different reactions</a> to COVID-19 vaccines. Earlier this year, 23andMe published a study in<a href="https://www.nature.com/articles/s41588-021-00986-w"> Nature Genetics</a> that identified genetic variants associated with the loss of smell or taste due to COVID-19. That paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.
The Harvard study and the preliminary 23andMe data offer more insight into the perplexing nature of long COVID. But the studies also offer another illustration of the broader health impacts of these kinds of psychological stressors.   
Find the full Harvard study<a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796097"> here</a>.

A logo for 23andMe's COVID-19 Research Study

More on Psychological Distress and Risk for Long COVID

A look by researchers of 23andMe’s internal data from customers who consented to participate in research reveals that some gut health issues affect females differently than males and that these conditions have a bigger impact on people of some ethnicities than others.
The insights come from 23andMe internal data regarding two relatively common gut health conditions, irritable bowel syndrome (IBS) and diverticulitis. The findings confirmed what we already know about common gut health issues and their importance in overall health. It also highlights that genetics plays a big role in the likelihood of developing one of these conditions. 
The data shows that the prevalence of these conditions is more common within some ethnicities. Beyond that, certain genetic variants can increase an individual’s risk compared to others of the same ethnicity. Noting the role that ethnicity and genetics play would be important considerations in assessing an individual’s likelihood of developing either IBS or diverticulitis.
This snapshot of 23andMe data from customers who consented to participate in research looks at just two of the<a href="https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases"> many digestive conditions</a> related to gut health, but they are two conditions that impact millions of people worldwide. 
<h6>The 23andMe Data on IBS</h6>
In the case of IBS, estimates are that it impacts<a href="https://aboutibs.org/what-is-ibs/facts-about-ibs/"> between 25 and 45 million people</a> in the US alone, and it impacts females at a much higher rate. Symptoms often include abdominal pain, cramping, bloating, and changes in bowel function, including diarrhea, constipation, or both.
<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-30700" src="http://35.88.189.111/wp-content/uploads/2022/11/ibs-by-age-and-sex.png" alt="" width="550" height="662" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/11/ibs-by-age-and-sex.png 550w, https://blogcms.23andme.com/wp-content/uploads/2022/11/ibs-by-age-and-sex-249x300.png 249w" sizes="auto, (max-width: 550px) 100vw, 550px" />
A study published in <a href="https://www.nature.com/articles/s41588-021-00950-8">Nature</a> in late 2021 found that IBS symptoms may be caused by the same biological processes that trigger anxiety, depression, and insomnia. It’s not that IBS causes anxiety or mood disorders but that certain genes are involved in the progression of these conditions. Several studies also indicate that these conditions impact females more than males.
According to data from 23andMe, females are about two and a half times more likely to develop the condition than males. (See figure that compares males and females with IBS by age.) While it’s well documented that<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175559/"> sex can impact the likelihood</a> of an individual’s likelihood of developing IBS, far less is known about the role genetics play in this common condition.
Perhaps even more than sex differences, ethnicity and genetics impacts the likelihood of developing IBS. According to new modeling done by 23andMe scientists, both genetics and ethnicity have a big impact on the likelihood of an individual being diagnosed with IBS. In some cases, they present a much bigger risk than previously published non-genetic factors.
In looking at ethnicity, people with largely Latino or largely European ancestry have the highest likelihood of developing IBS compared to those of other ethnicities. For example, people with mostly European ancestry are almost three times more likely to develop IBS than those of mostly East Asian ancestry. 
<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-30702" src="http://35.88.189.111/wp-content/uploads/2022/11/prevelance-of-ibs-by-ethnicity.png" alt="" width="550" height="452" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/11/prevelance-of-ibs-by-ethnicity.png 550w, https://blogcms.23andme.com/wp-content/uploads/2022/11/prevelance-of-ibs-by-ethnicity-300x247.png 300w" sizes="auto, (max-width: 550px) 100vw, 550px" />
<h6>Statistical Modeling</h6>
When researchers stratified the data and looked at individuals with a higher genetic likelihood of developing IBS — based on statistical modeling that used more than 12,000 genetic markers associated with IBS — compared to those with the least likelihood, the differences were stark. 
For example, people with predominantly Latino ancestry who also were in the highest genetic likelihood* category for IBS are four and a half times more likely to be diagnosed with IBS than Latinos with the lowest genetic likelihood.** If you look at people with primarily European ancestry who are also in that higher genetic likelihood category,* they were more than three and a half times more likely to be diagnosed with IBS than people of European ancestry at the lowest genetic likelihood.**
Why is this distinction important?  
Because it shows the outsized impact that genetic factors play on the likelihood of IBS. If you were to graph the polygenic risk for IBS, you’d see a bell curve distribution. Most people would have an average risk or be in the middle of that curve. But at the ends of this curve would be those with the least risk and the most risk.
For those with the highest genetic likelihood* — in the top five percent — the odds that they may develop IBS are quite high when compared to those at the lowest likelihood.** That information on their genetics could be very important for them and their provider in managing their health.
<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-30703" src="http://35.88.189.111/wp-content/uploads/2022/11/odds-of-developing-ibs-among-those-at-highest-genetic-risk.png" alt="" width="550" height="764" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/11/odds-of-developing-ibs-among-those-at-highest-genetic-risk.png 550w, https://blogcms.23andme.com/wp-content/uploads/2022/11/odds-of-developing-ibs-among-those-at-highest-genetic-risk-216x300.png 216w" sizes="auto, (max-width: 550px) 100vw, 550px" />
<h6>23andMe Data on Diverticulitis </h6>
23andMe’s data on diverticulitis confirms some of what we already know but also offers up a few surprises.
As with IBS, both ethnicity and genetics play an important role in the likelihood of developing diverticulitis. While it is relatively common, many people don’t know much about diverticulitis.
It occurs in the intestinal tract, where weak sections of the intestines lead to small bulges or pouches that become inflamed. These pouches, most often found in the large intestine (also called the colon), are called “diverticula.” They are common, especially as we age, but do not cause problems.
It’s estimated that more than half of people in the United States over 60 have diverticula and most likely never have any issues. But fewer than five percent of those individuals will develop inflammation in these pouches, a condition called “diverticulitis,” according to the<a href="https://www.niddk.nih.gov/health-information/digestive-diseases/diverticulosis-diverticulitis/definition-facts"> National Institutes of Health.</a> This can lead to symptoms such as abdominal pain, vomiting, fever, constipation, or diarrhea. More serious complications, such as blockages or perforations, can lead to hospitalization.
<h6>Diverticulitis and Ethnicity</h6>
While females were more likely to have been diagnosed with diverticulitis, the difference between males and females was less profound than that for IBS. And in the case of diverticulitis, the likelihood of developing the condition increases considerably as people age, according to the data.
People of European ancestry had the highest prevalence for diverticulitis and those of South Asian ancestry the lowest among individuals we studied.
<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-30713" src="http://35.88.189.111/wp-content/uploads/2022/09/prevalence-of-diverticulitis-by-age-and-sex.png" alt="" width="550" height="662" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/09/prevalence-of-diverticulitis-by-age-and-sex.png 550w, https://blogcms.23andme.com/wp-content/uploads/2022/09/prevalence-of-diverticulitis-by-age-and-sex-249x300.png 249w" sizes="auto, (max-width: 550px) 100vw, 550px" />
Looking at genetic likelihood of developing the condition, 23andMe data indicates that people with North African ancestry and Western Asian ancestry (Arabs, Kurds, Persians, and people from Anatolia for example) with the highest genetic risk* for being diagnosed with diverticulitis are about seven times more likely to be diagnosed with diverticulitis than those with the lowest genetic risk.**  
People of mostly European ancestry with the highest genetic risk* are five and a half times more likely to be diagnosed with diverticulitis based on their genetics than those with the lowest genetic risk.** People with mostly East or Southeast Asian ancestry who are at the highest genetic risk* for diverticulitis are five times more likely to be diagnosed with diverticulitis than those with the lowest genetic risk.**
<h6>Wrapping Up</h6>
This snapshot of 23andMe data on two gut health conditions reveals something many haven’t fully understood. It&#8217;s not just that genetics plays an important role in risk, but a person&#8217;s genetics together with their ethnicity matter. 
*Highest risk category: 5% of a given ethnicity, for example, Latino, with the highest genetic risk of being diagnosed with a condition
**Lowest risk category: 5% of a given ethnicity with the lowest genetic risk of being diagnosed with a condition.

Some Data to Digest About Gut Health

Listening to those with a rare disease, a common refrain is that they often feel isolated, unheard, and alone.
But they’re not alone.&nbsp;&nbsp;
<h6>Much to Learn</h6>
While each rare disease is by definition uncommon — affecting fewer than 200,000 people — there are more than 7,000 known rare diseases. There are more than 300 million people worldwide who have a rare disease. Yet because these rare diseases are unique and affect small groups of people, the conditions are difficult to study.&nbsp;
Disease research can sometimes be a numbers game, and research into rare diseases is often stymied as scientists struggle to gather enough individuals with the condition who are able to participate in their research. While we know that about 70 percent of rare diseases are genetic, there is so much we don’t know about these conditions. Only about 5 percent of all rare diseases have approved treatments.&nbsp;&nbsp;
<h6>Potential for Insight</h6>
23andMe hopes to change that. Part of our mission as a company is to focus our therapeutics efforts on conditions with unmet needs and to maximize our chances of discovering novel genetic insights to help in that search.&nbsp;
In the last few years, our researchers have discovered how powerful our unique research platform is for making important discoveries about these rare conditions. People with rare diseases are not limited by geography, and can easily participate in research if they choose, while our scientists can leverage online tools and data on a massive scale, to study a broad range of conditions.
“We have the potential of making genetic findings for several rare diseases for which there currently is very little known,” said John Matthews, Ph.D., M.D., and the Senior Clinical Development Fellow on 23andMe’s Therapeutics team.
<h6>23andMe’s Rare Disease Research Study</h6>
23andMe’s Rare Disease Research Study will start with a handful of rare diseases, recruiting individuals to participate in innovative genetic research around —<a href="https://www.23andme.com/systemic-sclerosis-study/"> systemic sclerosis</a> (a study we first started in 2021), ANCA-associated vasculitis, pemphigus vulgaris, and dermatomyositis.&nbsp;
<ul>
<li style="font-weight: 400;" aria-level="1">Systemic sclerosis causes the hardening of the body’s connective tissue.</li>
<li style="font-weight: 400;" aria-level="1">ANCA-associated vasculitis (AAV) is actually a group of autoimmune diseases that are characterized by inflammation of small vessels.&nbsp;</li>
<li style="font-weight: 400;" aria-level="1">Pemphigus vulgaris is an autoimmune disorder that involves blistering and erosion of the skin as well as the mucous membranes.</li>
<li style="font-weight: 400;" aria-level="1">Dermatomyositis is an inflammatory disease marked by muscle weakness and a distinctive skin rash.</li>
</ul>
In addition to these four conditions, 23andMe will expand another existing rare disease study on <a href="https://www.23andme.com/idiopathic-pulmonary-fibrosis/">&nbsp;idiopathic pulmonary fibrosis</a>, which causes irreparable scarring of the lungs that progressively worsens lung function. The study now will broaden to include other types of lung fibrosis as part of this program.&nbsp;
The hope is that this work will lead to discoveries and insights into possible new treatments. We plan to slowly expand the number of conditions we study in the coming months.
In typical rare disease research, scientists have relied on very small cohorts of perhaps a few dozen individuals or studied members of the same family who all might share a rare condition. But that makes it very difficult to gain new insight into genetic variants that were previously unknown to be associated with these rare conditions.
<h6>A Revelation</h6>
In what at the time was believed to be the largest genetic study of rare diseases, 23andMe published research in 2021 explaining how the company is uniquely positioned to<a href="https://blog.23andme.com/23andme-research/new-way-to-study-rare-disease/"> study rare diseases.</a>&nbsp;
Using data from more than 1.6 million research participants, including 19,000 who reported a rare disease diagnosis, 23andMe scientists conduct genome-wide association studies on 33 different rare diseases. The 23andMe study is the first Genome-Wide Association Study (GWAS) ever done for a few of these rare conditions. The study identified new genetic associations for each. The research was a revelation. Finding these associations offers scientists a deeper understanding of the biological pathways for the conditions and offers the possibility for identifying potential treatments.
“It was a surprise for us when we were able to find genetic associations in studies of rare diseases with only tens of affected individuals,” said 23andMe senior scientist in statistical genetics, Suyash Shringarpure, Ph.D., who worked on the study. “Another surprise was finding that common genetic variants show association with rare disease risk. Previously, it has been found that rare genetic variants cause rare diseases, so this was unexpected.”
You can learn more about 23andMe’s Rare Disease Study by following the links to the disease-specific landing pages below:
<ul>
<li style="font-weight: 400;" aria-level="1"><a href="https://www.23andme.com/rare-disease-research-study/systemic-sclerosis/">Systemic sclerosis</a>&nbsp;</li>
<li style="font-weight: 400;" aria-level="1"><a href="https://www.23andme.com/rare-disease-research-study/anca-associated-vasculitis/">ANCA-associated vasculitis</a>&nbsp;</li>
<li style="font-weight: 400;" aria-level="1"><a href="https://www.23andme.com/rare-disease-research-study/pemphigus-vulgaris/">Pemphigus vulgaris</a></li>
<li style="font-weight: 400;" aria-level="1"><a href="https://www.23andme.com/rare-disease-research-study/dermatomyositis/">Dermatomyositis</a></li>
</ul>
<h6></h6>

23andMe Launches Rare Diseases Study

A new genetic study identified five regions in the human genome associated with susceptibility to pneumonia, a leading cause of death worldwide.
Published in the journal<a href="https://www.nature.com/articles/s41467-022-31473-3"> Nature Communications</a>, the study also found a surprising link between the risk of pneumonia and psychiatric conditions, such as schizophrenia, bipolar disorder, and major depression.
There are several types of pneumonia, but the most common involve bacterial or viral infection in the lungs. The condition can be deadly for those most physically vulnerable, particularly the elderly and young children. Many of those hospitalized for COVID-19 also end up having to be treated for pneumonia.
<h2>Five Genetic Regions</h2>
This study was led by researchers at the University of Newcastle in Australia. It included data from over half a million individuals and is believed to be the largest genomic study of pneumonia ever done. The research included data from 23andMe customers who consented to participate in research and data from the<a href="https://www.finngen.fi/en"> FinnGen</a> consortium.
The researchers identified five genetic regions associated with pneumonia. Some previously identified associations within human leukocyte antigen (HLA) genes were among those. 
The HLA genes are the hundreds of genes on chromosome 6 that regulate the body’s immune system. The HLA gene also regulates the response to invading pathogens like viruses and bacteria. 
<h2>Role of Inflammation</h2>
The team also found three new associations in genes related to inflammation and immunity and another new association in the gene MUC5AC. The gene is in a cluster of genes that regulate the production of mucin proteins in the body. Mucin proteins make up mucus, the substance that lubricates and protects the lining of the airways, digestive tract, and reproductive system. The up-regulation of MUC5AC may exacerbate pneumonia by inducing inflammation in the airways.
According to the researchers, the link between the genetic risk for pneumonia and psychiatric conditions may be related to inflammation.
“I think it&#8217;s surprising, but in some ways, it’s not, as there are thought to be inflammatory risks for mental illness,”<a href="https://www.newcastle.edu.au/newsroom/featured/pneumonia-risk-signals-potential-for-precision-medicine"> said Murray Cairns,</a> one of the paper’s co-authors and a principal investigator at the University of Newcastle’s HMRI Precision Medicine Research Program. “(Inflammation) is a well-known risk factor for psychiatric illness, so it&#8217;s potentially a risk shared between those disorders.”
The researchers acknowledge that much more must be done to understand the link between pneumonia and mental illness. However, in the paper, they hypothesize that the connection may be related to HLA genes and either their overreaction, inflammation, or inadequate response to an infection.
Understanding the role of this link with inflammation and the genetic associations for pneumonia could help researchers look for new treatments.
Find the complete study in the journal<a href="https://www.nature.com/articles/s41467-022-31473-3"> Nature Communications.</a>

A New Genetic Study on Pneumonia

A very large genetic study of insomnia has identified hundreds of genes associated with the condition that is also linked to such things as depression, anxiety, schizophrenia, as well as metabolic disorders.
The scientists who worked on the study suggest that the breadth of those links likely indicates that there are different genetic subtypes for the condition. It’s estimated that as many as<a href="https://pubmed.ncbi.nlm.nih.gov/28348990/"> 30 percent of adults</a> have insomnia, which is defined as an inability to fall asleep at least three times a week over several months.
<h6>Large Study </h6>
Published in the journal Nature Genetics the<a href="https://www.nature.com/articles/s41588-022-01124-w"> study</a> included data from more than 2.3 million people, more than half a million of whom reported having insomnia and the remaining 1.8 million without the condition who were used in this research as controls. 
This study almost doubled the size of the previous largest genome-wide association <a href="https://blog.23andme.com/23andme-research/genetics-of-insomnia-more-similar-to-psychiatric-conditions-than-to-other-sleep-traits/">study on insomnia</a> that was conducted by some of the same scientists. Danielle Posthuma, a professor at Vrije University in Amsterdam, again led it at Vrije University in Amsterdam.
Posthuma and her co-authors explained in this paper that the current work suggests that &#8220;for extremely polygenic traits such as insomnia, increasing sample size does lead to an increase in detected (single nucleotide polymorphisms), loci, genes, and pathways, providing more confidence in existing and novel mechanisms.&#8221;
<h6>Many Genes Involved</h6>
At the same time, the additional data in this study did not improve the predictive power for insomnia. This is in part due to the highly polygenic nature of insomnia, meaning that there are many, many genetic variants associated with the condition that have yet to be identified. Insomnia is estimated to be the third most polygenic trait behind major depressive disorder and educational attainment, according to the researchers for this study.
The study identified 289 genes involved in insomnia, but that total still only explains about 10 percent of the heritability of the condition. Some of the genes associated with insomnia appeared linked to metabolic or psychiatric conditions.
Other studies indicate that about<a href="https://pubmed.ncbi.nlm.nih.gov/18979946/"> three-quarters of adults</a> with depression suffer from insomnia. 
23andMe does not have a genetic health report on insomnia, but it does have a collection of reports on such things as <a href="https://www.23andme.com/topics/wellness/deep-sleep/">Deep Sleep</a>, <a href="https://www.23andme.com/topics/wellness/sleep-movement/">Sleep Movement</a>, and Wake Time in a “sleep hub” meant to look at how your genetics may play a role in the quality of your sleep.
You can read the full insomnia study in<a href="https://www.nature.com/articles/s41588-022-01124-w"> Nature Genetics.</a>

New Genetic Study on Insomnia

In late 2020, 23andMe launched a genetic study of systemic sclerosis, a rare autoimmune disease that results in the hardening and thickening of the skin and other organs.
Within 18 months, we’ve met our goal of recruiting more than 1,500 individuals with systemic sclerosis to participate in this study. We did this through online recruitment and with help from a collaboration with the Scleroderma Research Foundation, and our drug discovery collaboration partner GSK, who provided funding and expertise. 
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 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="210" height="210" src="https://blogcms.23andme.com/wp-content/uploads/2020/11/Scleroderma-Feed-Icon@3x.png" alt="" class="wp-image-28608" srcset="https://blogcms.23andme.com/wp-content/uploads/2020/11/Scleroderma-Feed-Icon@3x.png 210w, https://blogcms.23andme.com/wp-content/uploads/2020/11/Scleroderma-Feed-Icon@3x-150x150.png 150w" sizes="auto, (max-width: 210px) 100vw, 210px" /></figure>
 
<h6>Recruiting to Study the genetics of systemic sclerosis</h6>
Simply reaching our recruitment goal so quickly is an important milestone.
Like many rare diseases — defined as conditions that affect<a href="https://rarediseases.info.nih.gov/about"> fewer than 200,000</a> individuals in the United States — there is currently no cure or effective treatment for systemic sclerosis. And like many rare diseases, the rarity of this condition makes it challenging for scientists to study. As with many of the more than 7,000 known rare diseases, it is often difficult to find enough people with a rare disease, or enough who are able to participate in research studies. Historically, research on these conditions has been limited and slow.
23andMe’s unique research model allows for online recruitment and participation, which makes it that much easier.
<h6>A snapshot of our research participants</h6>
While there is still much work to do, we want to mark this recruitment milestone. And as we close our recruitment and begin this next phase of the study, we’re sharing a little bit about those participating in our research.
In all, 1,594 people living with systemic sclerosis consented to participate in our research. Although we haven’t yet begun the study, we’ve begun to characterize the cohort of research participants and we’ve already learned a little bit from them.
The condition is more common among women; indeed, 95 percent of the participants in our study are female. We’ve learned that the median age of onset of symptoms among our participants is 35 for those with what’s called primary Raynaud’s phenomenon. For onset of other systemic sclerosis symptoms, the median age of onset is 38 among those participating in 23andMe’s study. 
Raynaud’s phenomenon is the most common symptom for those with systemic sclerosis.  It’s characterized by what’s called vasospasms or spasms of the blood vessels that are triggered by cold temperatures or stress. This can lead to discoloration of the fingers, numbness and pain. In some cases, it can also lead to ulcers on the fingers. (Just note that people who do not have systemic sclerosis can also develop Raynaud’s.)
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 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="584" height="598" src="https://blogcms.23andme.com/wp-content/uploads/2022/08/Sscl-Bar-Graph.png" alt="" class="wp-image-29978" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/08/Sscl-Bar-Graph.png 584w, https://blogcms.23andme.com/wp-content/uploads/2022/08/Sscl-Bar-Graph-293x300.png 293w" sizes="auto, (max-width: 584px) 100vw, 584px" /></figure>
 
<h6>Most Common Symptoms</h6>
To give readers a sense of how difficult systemic sclerosis can be for those living with it, we&#8217;re sharing some of the most common symptoms reported by our participants.
Almost half of participants, 48 percent, have had sores or ulcers on their fingers. Another serious symptom is called “interstitial lung disease,” essentially scarring of the lungs, and 30 percent of participants reported having this. Lung scarring can make it harder to breathe and get oxygen into your bloodstream.
About 14 percent of participants reported having pulmonary arterial hypertension, or high blood pressure caused by restrictive blood flow in the lungs. Finally, about 3 percent of participants reported having one of the most serious complications from systemic sclerosis, renal crisis, which can lead to renal failure or congestive heart failure. 
<h6>Studying the Genetics of Systemic Sclerosis</h6>
As our researchers begin the hard work of this study, they continue to focus on the goal that this work will generate genetic insights for potential treatments.
This study will allow our researchers to study systemic sclerosis at scale and allow those living with this condition to participate in research that could provide invaluable insight that may lead researchers to a future treatment discoveries.
While we know that about 70 percent of rare diseases are genetic, there is so much we don’t know about these conditions. Only about 5 percent of all rare diseases have approved treatments. But by working to uncover new genetic insights to conditions like systemic sclerosis, we hope to add to the list of approved treatments to address this unmet need. 
With the additional consent of participants in the study, we plan  to share the data from this study with qualified researchers from academia or biotech labs through the Database of Genotype and Phenotypes (<a href="https://www.ncbi.nlm.nih.gov/gap/">dbGaP</a>). This  repository is sponsored by the <a href="https://www.nih.gov/">National Institutes of Health (NIH)</a>. The NIH’s dbGaP archives and distributes data from studies investigating the relationship of genotype and phenotype in humans.

Recruitment Goal Met for Systemic Sclerosis Genetic Study

A new genetic study suggests drinking coffee during pregnancy does not negatively affect birthweight, nor does it increase the risk of a miscarriage, stillbirth, or premature birth.  
The<a href="https://academic.oup.com/ije/advance-article/doi/10.1093/ije/dyac121/6605011?login=false#358171832"> study</a>, by researchers at the University of Queensland in Australia and the University of Oslo, counters the advice often given during pregnancy to avoid caffeine. That advice was based on observational studies that did not separate coffee drinking from the harmful effects of behaviors like smoking, drinking alcohol, or poor nutrition.  

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="681" src="https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-1024x681.jpg" alt="" class="wp-image-26590" srcset="https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-1024x681.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-300x199.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-768x511.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-880x585.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans-1180x784.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2018/10/coffee-beans.jpg 1256w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
<h6>Randomized Stidy</h6>
But in this study the researchers focused solely on the effects of drinking coffee. 
 They used data from several sources, including UK Biobank and from 23andMe customers who consented to participate in research. Ideally, the researchers would have isolated the effects of drinking coffee by doing a randomized trial. This would have required recruiting a very large group of pregnant women and then requiring some to drink coffee, and the others would not be allowed to drink coffee. Then researchers would monitor the effect on their pregnancies. For several reasons, that study design is not feasible in this case. So instead, the researchers used Mendelian randomization to mimic a randomized trial. They did this by first looking at genetic variants associated with drinking coffee and then seeing if they also affect pregnancy outcomes.
Using this genetic analysis, the researchers found no causation between drinking coffee during pregnancy and pregnancy risks for miscarriage, stillbirth, or premature birth. 
<h6>Moderation</h6>
At the same time, the study only looked at a handful of adverse pregnancy outcomes, leaving the possibility that drinking coffee could affect other aspects of a baby’s development.
“For that reason, we don’t recommend a high intake during pregnancy, but a low or moderate consumption of coffee,”<a href="https://www.uq.edu.au/news/article/2022/06/genes-reveal-coffee-safe-during-pregnancy"> said Dr. Gunn-Helen Moen</a>, a lead researcher for the study.
This research used genetic data from the Coffee and Caffeine Genetics Consortium, the<a href="https://www.ukbiobank.ac.uk/"> UK Biobank</a>, the<a href="http://www.bristol.ac.uk/alspac/"> Avon Longitudinal Study of Parents and Children</a>, and customers from 23andMe who consented to participate in research.
The study was published in the<a href="https://dx.doi.org/10.1093/ije/dyac121"> International Journal of Epidemiology</a>.

Research — Page 11