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Before genetics came into the picture, researchers interested in introducing agriculture to Europe had only the archaeological record to go on – a limited collection of primarily stone and bone artifacts that left much room for interpretation. But as researchers began applying population genetics to the question of how farming spread across Europe, beginning with the work of <a id="yenv" title="Luca Luigi Cavalli-Sforza" href="https://www.ncbi.nlm.nih.gov/pubmed/258176?ordinalpos=7&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank" rel="noopener">Luca Luigi Cavalli-Sforza</a> nearly 40 years ago, there began to be hope for a better understanding of how agriculture spread through the continent beginning about 10,000 years ago.
<h2>The Spread of Agriculture</h2>
Decades of genetic research have produced some clarity. But geneticists have also created their own new sources of debate surrounding the spread of agriculture.
Over the years, two schools of thought have jockeyed for dominance: one argues that farmers from the Near East came into Europe around 10,000 years ago, spreading both their knowledge of farming AND their descendants throughout the continent.
Known as the &#8216;Demic Diffusion Model,&#8217; this hypothesis predicts that most of today&#8217;s Europeans trace their ancestry to early farmers from the Near East.   The alternative hypothesis, dubbed the &#8216;Cultural Diffusion Model,&#8217; argues that while the practice of farming likely spread from the Near East into Europe, the farmers themselves did not.   Instead, the technology was passed along from settlement to settlement until it reached northern Europe 5,000 years later. It predicts most modern Europeans should trace their ancestry to the original Stone Age inhabitants of Europe.
<h2>The Balkan Link</h2>
As the debate has continued, newer studies have begun breaking the puzzle down into more manageable pieces, looking at particular regions within Europe to see how farming changed the demographics on a more regional level.
This is precisely what new research published in the European Journal of Human Genetics seeks to do by examining the genetic history of the Balkans in Eastern Europe to work out what was happening there nearly 10,000 years ago.
The study&#8217;s authors, including Stanford professors and 23andMe scientific advisers Drs. Peter Underhill and Roy King focused on the Balkans chiefly because the archaeological record in this area hints at interactions between farmers from the east and the hunter-gatherers who were already living there.   The researchers chose to examine the Y-chromosome, which is passed down from father to son, to see if any traces of such interactions remained in people living in the Balkans today.   They sampled more than 1,200 men from Greece, Albania, Slovenia, and many other countries on the Balkan Peninsula and throughout Eastern Europe.
<h2>Early Haplogroups</h2>
They found three major Y-chromosome haplogroups (clusters of men with deep ancestry along the paternal line). One group pre-dated the arrival of agriculture into the region, a second arrived along with agriculture, and a third fell somewhere in between.
Specifically, more than 60% of those sampled belonged to branches of either haplogroup I or haplogroup R, both of which are believed to have arrived in Europe tens of thousands of years ago.   In addition, a unique branch of haplogroup E is found at levels of 15-25% among the men tested, but only in those people hailing from the southern Balkans (such as Greece or Macedonia).   Finally, up to one-fifth of the men tested fell into haplogroup J, which is common in the Near East and thought to be closely associated with Mediterranean seafarers and agriculture&#8217;s origin and spread.
What do these figures mean?
First of all, it is clear that over half of the men in the Balkans and Eastern Europe belong to haplogroups that pre-date the arrival of agriculture in the area.   These men&#8217;s paternal ancestors likely trace back to the Mesolithic hunter-gatherers.   On the other hand, the 20% of men belonging to Haplogroup J likely trace their ancestry to the same Near Eastern populations where agriculture originated.
<h2>Hunter-Gatherers and Farmers</h2>
So it stands to reason that &#8211; because the authors&#8217; samples contain both hunter-gatherer and farmer haplogroups &#8211; there was likely some kind of interaction between the two populations when they came into contact with each other nearly 10,000 years ago.   More importantly, it reveals that the spread of farming into Europe cannot be pigeonholed into either the Demic Diffusion or Cultural Diffusion Model.   Its spread is far more complex &#8211; and intriguing &#8211; than many initially thought.
But what about the men who traced their ancestry to that sub-branch of haplogroup E, which is typical of North or East Africans; what is it doing in the Balkans?   Haplogroup E has a unique history, stretching back some 40,000 years to East Africa. From where men carrying it expanded into the Nile Valley.   The authors believe this branch of Haplogroup E exited Africa almost 16,000 years ago, well before the arrival of farming, making it to the southern Balkans a few thousand years later.   Men bearing the haplogroup may have been among the first converts to agriculture when Neolithic farmers arrived in the area a few thousand years after that.
So it would seem that by using genetics to piece together ancient interactions between Mesolithic hunters and Neolithic farmers, we are actually left with new questions surrounding the arrival of Haplogroup E.
Who were these men who carried it?   What made them expand from the Nile Valley into the Balkans just before the arrival of farming?   And did their presence in the Balkans influence interactions between the hunter-gatherers and the farmers from the Near East?
Once again, research into the genetic signatures of the first farmers has given us both new answers and new questions.

23andMe Blog

23andMe Blog Team

New Genetic Discoveries Shed Light on the Spread of Farming in Eastern Europe

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Every year, about half of the more than one million people in the United States who have a heart attack survive. But because the first heart attack increases their risk for another one, these people must make major adjustments in their lives to keep their hearts healthy in the future.
In addition to adopting a healthy diet, quitting smoking and losing weight, most people who’ve had a heart attack take medications to help further reduce their risk. Clopidogrel – sold under the trade names Plavix, Iscover, Clopilet and Ceruvin – is a drug commonly prescribed (often in combination with aspirin) to help prevent platelets in the blood from forming clots that can block blood flow to the heart.
Clopidogrel is converted into its active form once it is inside the body. But some people carry genetic variants that reduce the activity of an enzyme central to this conversion process, which in turn reduces the amount of active clopidogrel in the bloodstream and the effectiveness of the drug in preventing clots. Three reports published online this week — two in the New England Journal of Medicine and one in The Lancet — show that genetic variants can increase the chances that a patient will suffer a second major cardiovascular event.

Jessica Mega and co-workers from Brigham and Women’s Hospital and Harvard Medical School in Boston tracked 1,477 subjects who had had unstable angina or a heart attack and were taking clopidogrel.
Their results, published in <a href="http://content.nejm.org/cgi/content/full/NEJMoa0809171" target="_blank" rel="noopener noreferrer">NEJM</a>, showed that those people who carried one or more copies of a function-reducing variation in the CYP2C19 gene that (referred to as *2, *3, *4 and *5) had 1.53 times the risk of having a heart attack, stroke or dying from cardiovascular causes compared to non-carriers. The risk of a stent-blocking clot (in those patients who had stents implanted during angioplasty to keep their arteries open) was increased three-fold.
The second <a href="http://content.nejm.org/cgi/content/full/NEJMoa0808227" target="_blank" rel="noopener noreferrer">NEJM</a> report, from researchers at several Paris hospitals led by Tabassome Simon, showed that in a group of 2,208 heart attack patients taking clopidogrel, carrying two CYP2C19 variants (any combination of *2, *3, *4, or *5) led to a 1.98 times increased risk of heart attack, stroke or death from any cause. Among the 1,535 patients who underwent angioplasty while in the hospital, having two function-reducing CYP2C19 variants increased the risk of cardiovascular events by 3.58 times.
Unlike the study from Mega et al, Simon and colleagues did not see an increased risk in those people with only one copy of a CYP2C19 function-reducing variant.
Finally, Jean-Philippe Collet and colleagues (also from Paris, France) followed the outcomes for 259 young (&lt; 45 years old) heart attack patients taking clopidogrel. Their results, published in <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61845-0/fulltext" target="_blank" rel="noopener noreferrer">The Lancet</a>, showed that having one or two copies of the CYP2C19*2 variant increased the risk of a second heart attack by 4.54 times. The risk of a stent-blocking clot increased 6.02 times.
Collet et al did not investigate the other CYP2C19 variants included in the other reports.
Although the magnitude of the effect of CYP2C19 variants was different in each report, all three did show that versions of the CYP2C19 gene that reduce its ability to activate clopidogrel also increased the risk of a second cardiovascular event in those patients who have already suffered one. Based on these results, both Simon et al and Collet et al suggest that genotyping patients might be a good alternative to the current practice of monitoring their platelet response to clopidogrel.
But in a <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61846-2/fulltext" target="_blank" rel="noopener noreferrer">commentary</a> accompanying the report in The Lancet, Dr. Robert Storey of the Cardiovascular Research Unit at the University of Sheffield School of Medicine, UK, argues that testing platelet function in patients is faster than genotyping, and has the added benefit of finding patients who are not responding to clopidogrel due to factors other than CYP2C19 variants, such as age, diabetes, renal failure and cardiac failure.
“Genotyping of patients with acute coronary syndrome is not necessarily the appropriate solution without further work to validate such an approach,” he writes.

Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack

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In genetic anthropology, mitochondrial DNA and the Y chromosome are the major players.
Scientists use these regions of our genome most frequently when tracing ancient and historical human migrations, and they are important tools for genealogists who use DNA to piece together their family trees.
<h2>X Marks the Spot</h2>
But another part of the human genome has recently started to prove itself as a window into our species&#8217; past: the X-chromosome.
Like both the mtDNA and the Y-chromosome, the X is passed from parents to children in such a way that scientists can use it to trace the deep ancestry of our species. However, only recently has the X-chromosome been used this way, and some of the early research has been somewhat inconsistent.
Now, the authors of a paper published in this week’s <a href="https://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.303.html" target="_blank" rel="noopener">Nature Genetics</a> believe they have perfected a way of using the X-chromosome to unravel details about the initial migration of humans out of Africa tens of thousands of years ago. Their results suggest that more men than women were involved in the exodus that initiated the peopling of the entire globe.
<h2>Why the X and not the Y?</h2>
One of the reasons analysis of the X-chromosome has not proven straightforward compared to the mtDNA or the Y-chromosome is that the way the X is passed down from one generation to the next differs depending on the child&#8217;s sex. Fathers pass on their X chromosomes to their daughters, but not their sons, while mothers pass one X chromosome to their children of both sexes. So, while any person&#8217;s X-chromosome came down to them along a specific lineage – just like their Y-chromosome and mtDNA – that path is impossible to trace.
<h2>The XX</h2>
However, the X chromosome does have one distinctive quality. Since men have one and women have two, any population with a 50/50 sex ratio will have three X chromosomes for every four of the 22 paired chromosomes. That means all other things are equal, and genetic diversity on the X-chromosome should be about three-quarters as much as on the non-sex chromosome.
To see if all has been equal in the history of the human species, researchers from Harvard, the Broad Institute, and the National Human Genome Research Institute analyzed the genotypes of people from around the globe. They looked for differences among the populations of Africa, Europe, and East Asia. Though they found the expected 75% X-chromosome diversity ratio within Africans, there was considerably less diversity among European and East Asians on the X compared to their 22 non-sex chromosomes.
Genetic Variation
<h2>What could all this mean?</h2>
First, a decrease in genetic variation is usually a sign of decreased population size.   Because it shows up in East Asians and Europeans but not Africans, the authors believe the decreased variation is a signal of a population bottleneck that occurred after humans left Africa for the first time nearly 60,000 years ago – but before the non-African populations diverged from each other.
However, the decreased genetic variation only seems to show up on the X-chromosome.   This, the authors speculate, may be due to some sort of sex-biased migration.   In other words, when humans first ventured outside of Africa and into Europe and Asia, there may have been more men on the move than women.   Scientists have long observed the same phenomenon when comparing the Y-chromosome to mtDNA; now researchers see the same phenomenon here with the X.

Using X-Chromosome to Trace Prehistoric Human Migrations

Since 23andWe debuted in May, we&#8217;ve asked our customers about all sorts of things: their hair color, <a href="https://www.23andme.com/topics/traits/earwax-type/">earwax consistency</a>, whether they tend to look on life&#8217;s bright side. Sometimes people have been surprised to learn that something like your susceptibility to motion sickness – or even which way the <a href="http://www.genetics.org/cgi/content/abstract/165/1/269" target="_blank" rel="noopener noreferrer">hair swirls</a> on top of your head – may be influenced by genetics.
Now we&#8217;re introducing three new surveys that ask our customers a few more thought-provoking questions that could help science understand more about genetics: 

<ol>
<li>Our new ancestry survey, &#8220;Where are You From?&#8221; inquires about the birthplaces of our customers, their parents and grandparents. We&#8217;re hoping the survey can help us do an even better job of correlating peoples&#8217; genetics to their ancestral homelands. It could also help us address questions geneticists have had little opportunity to ask in the past, such as how regional genetic differences within the United States may reflect the different ethnic backgrounds of the people who settled in the country. And finally, recent papers such as this <a href="http://hmg.oxfordjournals.org/cgi/content/abstract/17/R2/R143?maxtoshow=&amp;HITS=10&amp;hits=10&amp;RESULTFORMAT=1&amp;author1=Gregersen&amp;andorexacttitle=and&amp;andorexacttitleabs=and&amp;andorexactfulltext=and&amp;searchid=1&amp;FIRSTINDEX=0&amp;sortspec=relevance&amp;resourcetype=HWCIT" target="_blank" rel="noopener noreferrer">one</a> suggest that ancestry information can be vital to any study that tries to associate genes and traits.</li>
<li>Our second survey, &#8220;Health Habits,&#8221; asks about things like exercise, diet, smoking and drug use. It&#8217;s not that we want to determine whether there are genetic influences on whether a person smokes (though there probably are) so much as we&#8217;d like to know these things so we can see if they are more likely than genetics to account for the way people respond to certain surveys.</li>
<li>Researchers often struggle to distinguish between the contributions of nature and nurture when they study things like personality, IQ and athletic ability. Our final new survey – &#8220;What Do You Do?&#8221; – tries to account for some elements on the nurture side of the gene-environment equation.</li>
</ol>
These new surveys are a little different from some of the ones our customers have already taken. They&#8217;re not going to tell you if you&#8217;re less optimistic than average, or whether your tendency to sneeze in bright sunlight makes you a freak of nature (It doesn&#8217;t). But they&#8217;re just as critical to helping us reach our goal of advancing genetic research. So if you&#8217;re a 23andMe customer, we invite you to visit 23andWe and take our latest surveys. And if you haven&#8217;t joined the 23andMe community yet, we invite you to read more about <a href="https://www.23andme.com/research/" target="_self" rel="noopener noreferrer">23andWe</a> on our public site.

Three New Surveys from 23andWe Ask New Kinds of Questions

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The complications of type 2 diabetes — damage to the kidneys, nerves, eyes, and cardiovascular system — result from chronically high blood sugar.
While routine blood tests can provide a snapshot of blood sugar levels at one point in time, a more complete picture of long-term blood sugar control is obtained by measuring the extent to which sugar molecules are attached to hemoglobin, the oxygen-carrying protein found in red blood cells.
Measurement of this “glycated hemoglobin” reflects the total amount of sugar blood cells have been exposed to over the preceding eight to 12 weeks.
Clinical trials have shown that elevated, yet sub-diabetic, glycated hemoglobin levels increase risk for type 2 diabetes and cardiovascular disease. But although many studies have looked for genetic variants associated with type 2 diabetes itself, much less work has been done to uncover the genetic determinants of glycated hemoglobin levels.

Guillaume ParÃ© and colleagues from Harvard Medical School and Amgen, Inc., scanned the genomes of more than 14,000 apparently healthy (i.e. non-diabetic women) to look for SNPs that correlate with glycated hemoglobin. Their results, published online today in <a href="https://dx.doi.org/10.1371/journal.pgen.1000312" target="_blank" rel="noopener noreferrer">PLoS Genetics</a>, show that a variant in a gene never before linked to diabetes, HK1, is associated with glycated hemoglobin levels. Three other genes previously linked to diabetes and blood glucose concentration — GCK, SLC30A8 and G6PC2 — also harbored significantly associated variants.
According to the authors, the discovery of a link between the HK1 gene and glycated hemoglobin levels paves the way for further studies of the role of this gene in glucose metabolism and diabetes. The HK1 gene encodes the enzyme that carries out the first step of sugar breakdown in many cells throughout the body.
Together with the four variants, the researchers found to account for only a very small proportion of the total variance in glycated hemoglobin levels in the population — just 1.4%. Age, body mass index (BMI) and menopause status, on the other hand, explain about 9.5% of the variance.
Glycation of proteins in tissues other than red blood cells is thought to underlie the long-term complications of diabetes. The authors say it remains an open question whether the differences in glycated hemoglobin associated with the genetic variants identified in this study are paralleled in other parts of the body.
The SNPs associated with glycated hemoglobin levels are listed below by rsid#, gene, and the version associated with higher levels.
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Genetic Variants Linked To Blood Sugar Level

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More than two million Americans participate in clinical trials every year. Many may not realize when they sign up that the investigators running the trial are not required to tell them the results.
<h2>Re-Contacting Research Participants</h2>
The same goes for many genetic studies. In fact, there is often a specific prohibition against re-contacting participants once their samples have been taken.
At the very least, not informing participants of study results seems disrespectful of those who give of themselves to benefit medical research. More worrisome, it can mean that trial volunteers are missing out on the chance to learn information that could be important to their health.

<h2>Leveraging Online Tools</h2>
Changing the way research is done is no simple task. However, researchers at the University of Rochester Medical Center studying an experimental Huntington’s disease drug have shown that using a combination of targeted electronic communications and personal outreach can be a very effective way of disseminating clinical trial results to volunteers.
After analyzing the drug trial results (they turned out to have no effect), the researchers contacted participants by email and through various Huntington’s disease support groups and called them personally. There was also a teleconference in which study participants could ask the investigators questions.
Their results, published in the December issue of the <a href="http://archneur.ama-assn.org/cgi/content/short/65/12/1590" target="_blank" rel="noopener noreferrer">Archives of Neurology</a>, showed that within 24 hours, almost half of the study participants were able to learn the trial&#8217;s results. They reported great value in receiving personalized and accurate information from the research team.
<h2>Sharing Results</h2>
In the November issue of Genetics in Medicine, researchers from the Genetics and Public Policy at Johns Hopkins University showed just how hungry people are for their results.
In a survey of more than 4,600 people asked to consider whether or not they would take part in a large nationwide genetics study of 500,000 people, researchers found that three out of four people would be less likely to participate if they knew they would not receive their individual research results.
A scale project proposed in the John Hopkins survey could probably not rely on personal phone calls to inform participants of their results. The University of Rochester team benefited from having only a few hundred subjects who needed to be contacted. However, emails and posting on websites could certainly be used to satisfy subjects&#8217; demand for information.
“This eagerness suggests that researchers may have to look for practical ways to return results and abandon the paternalistic stance of protecting people from their research data,” the Johns Hopkins researchers wrote.
<h2>23andMe Research</h2>
We couldn’t agree more. That’s why we started <a href="https://www.23andme.com/research/">23andWe</a>, a new way of doing genetic research in which we hope to mobilize our customers as collaborators, advisers, and participants.
Sometimes, we’re able to return results right away. By answering just a few questions, you can find out if you’re an optimist or right-footed — and how you compare to everyone else who’s taken the survey.
But in addition to being exciting and fun, 23andWe surveys are designed to collect essential data for scientific research. We can’t know where this will lead us, but you will want to see how your data makes a difference. That’s why we’ll share the results of all our research and how your contributions are making an impact.

Turning Research Participants Into Research Partners

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In the current issue of <a href="https://www.nature.com/ng/index.html" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, two teams of researchers identify nine new genetic locations associated with obesity.
<h6>The Role of the Brain</h6>
Almost all of them are within or close to genes that are expressed in the brain, especially the part that regulates appetite.
&#8220;This underscores the importance of genes that regulate food intake over those involved in metabolism,&#8221; wrote a team of researchers led by Gudmar Thorleiffsson and G. Bragi Walters of deCODE Genetics.

Thorleiffsson et al. performed a two-step study that initially examined more than 30,000 people of European and African American descent from Iceland, Holland and the United States. It then narrowed down the list of promising genetic regions to 11 using a sample of 5,586 Danish individuals. Four of those regions – in or close to the genes FTO, MC4R, BDNF and SH2B1 – were already known to be associated with obesity.
<h6>Additional Genetic Variants Associated with Obesity</h6>
The other Nature Genetics paper, authored by the members of the Genetic Investigation of Anthropometric Traits (GIANT) consortium, initially looked for genetic links to obesity in more than 32,000 people of European descent, and then pursued their most promising leads in a second group of more than 59,000. The GIANT researchers confirmed two well-known obesity associations – the genes FTO and MC4R – and discovered an additional six.
Altogether, the two teams found nine new obesity-associated genetic variants; but none of them had a very substantial effect. For example, even someone who had the riskier version at all six locations found by the GIANT consortium would be only about four pounds heavier compared to average.
<h6>Small Effect Size</h6>
There are two possible explanations for the small effect of these new associations. Either there are dozens more associations with similarly small effects, or relatively rare genetic variations are much more important that more common ones in determining a person&#8217;s weight. Either way, finding those additional sources of genetic obesity risk is going to require studies even larger than the ones published this week in Nature Genetics.
23andMe customers who want to know their own genotypes at the new obesity-associated variants can use the following chart, which identifies the weight-increasing genotype for each SNP.

New Obesity SNPs Point to the Brain’s Role in Regulating Appetite

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Genome-wide association studies, the research projects that connect SNPs to different traits and conditions (and fuel much of the 23andMe Health and Traits feature), focus on fairly common genetic variations that generally have small effects on risk.
But critics of this type of research charge that studying common variation is of little value because it misses important information hiding in the genome in the form of rare mutations with large effects.
The results of a new genome-wide association study in the Old Order Amish of Lancaster, PA, may have bridged some of the gap between these two camps. In current issue of <a href="http://www.sciencemag.org/cgi/content/abstract/322/5908/1702" target="_blank" rel="noopener">Science</a>, researchers looking for SNPs associated with elevated triglycerides, a risk factor for heart disease, report finding a rare mutation in the Amish that could have important implications for preventing the condition in everyone.

About 5% of the isolated Amish community was found to carry one copy of a mutation that completely prevents a protein called apoC-III, encoded by the APOC3 gene, from being produced. ApoC-III prevents the breakdown of triglycerides in the bloodstream.
Mutation carriers had about 50% of the normal levels of apoC-III in their blood along with lower triglyceride levels, less “bad” LDL cholesterol and more “good” HDL cholesterol.
Carriers of the mutation were also much less likely to have coronary artery calcification (CAC), a measure of atherosclerosis. The mutation reduced the odds of having detectable CAC by 65%.
There is already a class of lipid-lowering drugs called fibrates that indirectly decrease the amount of protein made by APOC3. Other cholesterol drugs such as statins and niacin have also been associated with decreases in apoC-III levels. But the authors of the current study suggest that their discovery could mean that therapies aimed at directly reducing apoC-III levels will be useful in fighting heart disease.
Although 5% of the Amish carried the APOC3 mutation, it is thought to be rare or even entirely absent in the general population. Researchers believe the mutation was first introduced into the Amish community by a person who was born in the mid-1700’s.
The Amish are often used in genetic studies because they are an isolated and homogenous community with good genealogical records that date back to the time when they first migrated to North America.

Genetic Associations For Heart Disease Prevention

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Some families seem to have more than their fair share of illness, especially  in families with a propensity for autoimmune diseases, conditions that turn the body’s own infection-fighting cells against it, like type 1 diabetes and celiac disease.
These two autoimmune diseases often cluster together in families, and even in individuals. The prevalence of celiac disease in people with type 1 diabetes is five to 10 times higher than in the general population.
A report published this week by the <a href="http://content.nejm.org/cgi/content/full/NEJMoa0807917" target="_blank" rel="noopener">New England Journal of Medicine</a> shows that shared genetic risk factors are at least partially to blame. According to experts, these findings could help scientists understand more about the underlying biology of both diseases.

The researchers, led by Professor John Todd from the University of Cambridge, tested nine SNPs known to be associated with celiac disease in 8,064 type 1 diabetes patients, 9,339 controls, and 2,828 families with a child affected by the disease.
Four SNPs showed a significant association with type 1 diabetes. Three of these were novel findings. The association of a SNP in the SH2B3 gene with both diseases was already known from previous work.
When the researchers looked in the other direction, testing 19 SNPs known to be associated with type 1 diabetes in 2,560 people with celiac disease and the same 9,339 controls, two significant associations with celiac disease were found.
The total number of cross-acting SNPs was brought to seven when the researchers found that a variation called CCR5delta32 is also associated with the risk of developing both type 1 diabetes and celiac disease. CCR5delta32 is most famously associated with resistance to HIV infection.
Of the variants associated with both type 1 diabetes and celiac disease in this report, all but two had an effect in the same direction — the riskier version for one disease was also riskier for the other.
But the SNPs in IL18RAP and TAGAP had opposite effects. The T version of each SNP increased the risk for celiac disease, but decreased the risk for type 1 diabetes.
A SNP having a different effect on the risk for different diseases is not unheard of. The A version of in PTNP22 increases the risk of type 1 diabetes and rheumatoid arthritis, but has shown to be protective for <a href="https://www.nature.com/ng/journal/v40/n8/full/ng.175.html" target="_blank" rel="noopener">Crohn’s</a>.
In an accompanying editorial in <a href="http://content.nejm.org/cgi/content/short/NEJMe0809719v1" target="_blank" rel="noopener">NEJM</a>, Dr. Robert Plenge suggests that the SNPs identified in this study could theoretically be used to screen patients with one disease (i.e. celiac) to predict their risk of developing the other (i.e. type 1 diabetes). This type of screening, however, is controversial. Plenge also notes that because each SNP contributes only a small increase in risk, their use would not be likely to add much utility to current screening measures.
“The most important implication [of this kind of research] is likely to be the ability to define biologic pathways, many of which are unexpected, that cause disease. Over many years, such insight may lead to the development of novel therapies to treat, prevent, or even cure disease,” Plenge wrote.

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