<img loading="lazy" decoding="async" class="alignright size-full wp-image-4825" title="iStock_000007840761XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/09/iStock_000007840761XSmall.jpg" alt="iStock_000007840761XSmall" width="300" height="199" />
For as long as humans have lived in complex communities, cities and civilizations, they have divided and classified their societies. Those divisions have been based on age, gender, appearance or &#8211; in many cases &#8211; occupation. In many traditional societies artisans would share the same social status; as would soldiers, priests and workers in any number of other occupations.
<h6>Social Stratification</h6>
In antiquity, the status of a family rarely changed. If you were a farmer, your sons would be farmers, and so on. While today social status barriers are crumbling in many societies, in others they remain largely unchanged.
India&#8217;s complex social stratification, known as the caste system, has been one of the traditional cornerstones of society. Though urban Indians are shedding the caste labels of their parents and grandparents, many rural Indians &#8211; who make up 72% of the entire population &#8211; hold steadfast to the system. In small villages and towns, the Brahmin caste &#8211; consisting of scholars and priests &#8211; is still revered as one of the highest social strata. And members of the Dalit caste &#8211; formerly known as &#8220;Untouchables&#8221; &#8211; are still viewed as unclean and remain separated from others.
The rigidity of the system still present in rural India has made many wonder exactly how long castes have existed. Historical records are unclear, as early Hindu scriptures like the Bhagavad Gita are somewhat ambiguous when it comes to the topic. Some historians even propose that the caste system as we know it today is largely a construct of the English Colonial Era, arguing that the development of such a system could have been deemed necessary to instill order.
<h6>Genetic Analysis</h6>
Genetic analysis has also proven inconclusive, as analysis of small segments of the human genome has yielded different results. But a new study by geneticist David Reich and colleagues, published in the September 24 issue of <a href="https://www.nature.com/nature/journal/v461/n7263/abs/nature08365.html" target="_blank" rel="noopener">Nature</a>, takes a new approach to understanding the genetic history of India.
The core difference between Reich&#8217;s genetic analysis and previous studies is in the sheer amount of genetic material analyzed. Reich&#8217;s team examined more than 550,000 points across all segments of the human genome. In doing so, they hoped to obtain a more complete picture of Indian genetic history.
The research team analyzed the DNA of 132 individuals from India and neighboring regions, dividing them into 25 distinct groups based on geography, caste and language. They calculated how genetically &#8216;closed&#8217; each of these groups were. In the caste system it is rare to marry someone from another class, making caste societies very closed, or &#8216;endogamous.&#8217; If this endogamy continues over many generations, it will leave a behind a genetic signature for scientists to discover.
Reich and his team found such a signature, indicating a long history of endogamy in several of the groups. In fact, the research team calculated that the DNA of six of the groups can be traced back to just a few individuals who lived anywhere from 30 to more than 100 generations ago. Assuming a generation time of 25 years, that establishes the existence of the caste system in the range of 750 to more than 2,500 years ago – long before the British colonial era.
In a second analysis, Reich and his team examined how ancient migrations could have influenced the formation of castes. First the researchers divided the Indian groups into language families: Indo-European and Dravidian. Dravidian tongues, like Tamil and Malayalam, are mainly spoken in southern India and are believed to be a remnant of languages spoken by some of the earliest inhabitants of the region. Indo-European languages, like Punjabi and Urdu, are more common in the north. They are believed to have arrived with a migration of farmers from southwestern Asia or the Near East about 9,000 years ago.
Reich and his colleagues then compared the genetics of each of the Dravidian and Indo-European groups to a sample of European DNA. The team reasoned that, if Indo-European groups were really descended from the farmers, they would show more genetic similarity to the Europeans than the Dravidians.
Not surprisingly, the authors&#8217; hypothesis held true. The Indo-European speakers, like the Kashmiri Pandit and Vaish, were more genetically similar to Europeans. And because the majority of the upper castes speak Indo-European languages, while the lower ones tend to be Dravidian speakers, there could be a relationship between the arrival of Indo-European people and the formation of caste structure. Further evidence that an ancient caste system has permeated through India for thousands of years.

23andMe Blog

23andMe Blog Team

New Genetic Analysis Sheds Light on Origins of Indian Castes

<div id="attachment_4791" style="width: 360px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-4791" class="wp-image-4791 size-full" title="Glaucoma" src="https://blog-api.23andme.com/wp-content/uploads/2009/09/Glaucoma.jpg" alt="Glaucoma" width="350" height="206" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/09/Glaucoma.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/09/Glaucoma-300x177.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />Credit: National Eye Institute, National Institutes of Health</div>
Glaucoma is the second leading cause of blindness and is estimated to affect over 66 million people worldwide.
This group of diseases is typically caused by increased pressure in the eye, which slowly damages the optic nerve and leads to gradual vision loss and eventual, incurable blindness if left untreated.
The most common form of glaucoma is primary open-angle glaucoma or POAG. Prevalence of POAG among Caucasians is approximately 1-2%, but those with African ancestry develop glaucoma at rates five times higher and are four times more likely to become blind once they have the disease.
<h6> Glaucoma in Families</h6>
Family history and advanced age, in addition to high intraocular pressure, are known risk factors. Studies of families and monozygotic twins suggest a genetic basis, though the specific genes involved in the majority of disease cases have remained elusive.
To explore the genetic underpinnings of POAG in individuals of African descent, a group of researchers led by Xiaodong Jiao from the National Eye Institute in Bethesda and Kang Zhang from the University of California &#8211; San Diego recently partnered with the Ministry of Health in Barbados, West Indies to search for genetic variants associated with POAG in an Afro-Caribbean population with high rates of glaucoma.
<h6>New Study</h6>
In their paper, published online this week in the <a href="https://www.pnas.org/content/early/2009/09/23/0907564106.abstract">Proceedings of the National Academy of Sciences</a>, they report results from a region of the genome, chromosome 2p16, that previous studies have linked to the disease. When they analyzed SNPs in this region of the genome for the Barbados study group, they found two common variants significantly associated with glaucoma.
Although the case-control study population was fairly small &#8211; about 252 individuals total with glaucoma and 130 controls &#8211; the effects of the two SNPs were large when individuals had two copies of the high-risk version. Individuals with a T at both copies of had about 7 times higher odds of glaucoma, while individuals with a T at both copies of had almost 35 times higher odds.
The authors note that while their analysis of the 2p16 region suggests multiple genetic bases for POAG in Afro-Caribbeans, this region overlaps with one that was shown to contribute unequivocally to POAG in some families. They posit that the severity of the mutations caused by different variants in this genomic area may influence whether resulting POAG is due to a single gene, or the combined effects of many genes acting together to increase risk.
Further studies are needed to confirm the associations of and with POAG in larger populations, and to identify the genes directly involved in development of glaucoma.
(SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all the information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.)
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SNPwatch: Common Variants May Influence Glaucoma Risk in Individuals of African Descent

Human Prehistory 101:  Out of (Eastern) Africa

Alcohol addiction is associated with the brain’s reward system, which reinforces behaviors that feel good – like drinking – by releasing neurotransmitters such as dopamine and endorphins. With prolonged alcohol consumption, a person&#8217;s brain can gradually adapt to the point that excessive amounts of drinking are required in order to produce the same pleasure response, and alcohol addiction results.
That means genetic factors that influence the biochemistry of the reward pathway, as well as environmental factors that encourage alcohol consumption (such as peer pressure and stress) can increase a person&#8217;s alcoholism risk.
Researchers have long suspected that a combination of genetic and environmental causes can act together, increasing risk of alcohol addiction more than either acting alone. But so far little evidence has been found for such an effect.

A new paper to be published in the December issue of Alcoholism: Clinical and Experimental Research has found evidence for a synergistic effect between a genetic variation and level of education in a study of 700 Mexican-Americans. The prevalence of alcohol addiction among Mexican-Americans is relatively high; Mexican-American men report past heavy drinking at three times the rate of men belonging to other ethnicities.
The researchers, Yanlei Du and Yu-Jui Yvonne Wan of the University of Kansas Medical Center, measured three genetic variants associated with the function of chemicals involved in the brain&#8217;s reward system. They also looked at marital status and education level in the study participants.
The study found that of the three genetic variants, two were associated with severe alcoholism (defined by consuming more than 35 drinks per day).
o Having two copies of the A version of one of the SNPs, which is located on the opioid receptor gene OPRM1, increased the odds of severe alcoholism 2.16 times. 
o Having two copies of a variant in the DRD2 gene, which affects the structure of a receptor for the neurotransmitter dopamine, increased the risk of severe alcoholism 1.85 times.
Of the two environmental factors, only education level had an effect. Those with less than 12 years of education had 1.97 times the odds of severe alcoholism. (Having less than 12 years of education also increased a person&#8217;s odds of less-severe alcoholism by about the same amount.)
But when the researchers considered combinations of the three associations, they found that having two A copies of the OPRM1 SNP , combined with less than 12 years of education, increased a person&#8217;s odds of severe alcoholism 3.3 times.
The researchers suggest that a low education level may magnify the effects of the OPRM1 variant, or that higher education may mask its effects by improving brain function.
However, other factors might be responsible for the effect. For example, it is possible that those who attain an education past high school have other characteristics that make them less likely to become addicted to a substance.
There is no way yet to measure an individual’s vulnerability to alcohol addiction, and the complex interaction between genetics, education and other environmental factors must be further studied to clarify the causes of alcoholism in this and other ethnicities.

Evidence for Gene-Environment Interaction in Alcohol Addiction

<img loading="lazy" decoding="async" class="alignright size-full wp-image-4747" title="800px-HCV_prevalence_1999" src="https://blog-api.23andme.com/wp-content/uploads/2009/09/800px-HCV_prevalence_1999.png" alt="800px-HCV_prevalence_1999" width="433" height="189" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/09/800px-HCV_prevalence_1999.png 800w, https://blogcms.23andme.com/wp-content/uploads/2009/09/800px-HCV_prevalence_1999-300x132.png 300w, https://blogcms.23andme.com/wp-content/uploads/2009/09/800px-HCV_prevalence_1999-768x337.png 768w" sizes="auto, (max-width: 433px) 100vw, 433px" />
Unlike the flu virus, which the body is generally able to fight off completely, infection with hepatitis C is often chronic.   That means for most of the three to four million people worldwide who are newly infected each year the virus will persist in the body, where it greatly increases risk for chronic liver diseases including cirrhosis and cancer. The only treatment currently available – an almost year long course of drugs – often causes severe side-effects. Worse yet, it fails in about half of all patients.
Last month, a <a href="https://dx.doi.org/10.1038/nature08309" target="_blank" rel="noopener noreferrer">study</a> published online in the journal Nature showed that DNA variations in and around the IL28B gene influence whether a person chronically infected with the hepatitis C virus will fully respond to the standard treatment regimen. Now three new reports further support the importance of IL28B variations in the body&#8217;s response to hepatitis C, a finding that has implications for the future of hepatitis treatment and drug development.
An Australian group headed up by <a href="https://dx.doi.org/10.1038/ng.447" target="_blank" rel="noopener noreferrer">Vijayaprakash Suppiah</a> analyzed the DNA of more than 800 people with European ancestry from Australia, the UK, Germany and Italy infected with hepatitis C.   They found that having one or two copies of the less-common G version of , a SNP near the IL28B gene, doubled the odds that a person would fail to have a sustained response to treatment.
A group headed up by <a href="https://dx.doi.org/10.1038/ng.449" target="_blank" rel="noopener noreferrer">Yasuhito Tanaka</a> studied 326 Japanese hepatitis C patients and also found that predicts whether or not a person will respond to treatment.   In this population, however, the effect was much greater.   Carrying a G increased the odds of treatment failure by at least twelve times.
&#8220;This SNP has such a strong association with response that, in combination with other parameters, genotyping it and other genetic variants should be a useful part of   clinical management,&#8221; write Suppiah et al., who along with Tanaka et al. published their results online this week in the journal Nature Genetics.
Another study, this one published online in <a href="https://dx.doi.org/10.1038/nature08463" target="_blank" rel="noopener noreferrer">Nature</a>, found that variation near IL28B might be part of what allows a minority of people infected with hepatitis C to clear the virus naturally, without any treatment.
David Thomas and colleagues found that individuals with European or African ancestry were about three times more likely to spontaneously clear a hepatitis C infection if they carried two copies of the C version of than if they had CT or TT at this SNP.
Twenty-eight percent of the people with the CT or TT genotypes were able to fight off their hepatitis C infection without treatment, a number very close to the population average.   But 53% of those with the CC genotype were able to become naturally virus-free.
In a <a href="https://dx.doi.org/10.1038/461357a" target="_blank" rel="noopener noreferrer">commentary published in Nature</a>, Shawn Iadonato and Michael Katze express doubts about the importance of these new discoveries.
&#8220;Although these findings raise the tantalizing prospect of a more personalized approach to treating [hepatitis C] by tailoring treatment to patients who are most likely to benefit, the reality is more sobering,&#8221; they write.
Iadonato and Katze worry that testing for IL28B variations would not provide doctors with a straightforward yes-or-no answer to the question of whether a patient will respond to hepatitis C treatment.   This is because not all carriers of the advantageous versions of the variants clear the virus, nor do all patients lacking them fail to benefit from treatment.   Furthermore, they point out, there is currently no alternative hepatitis C treatment available.
What they do not consider, however, is how this new research may help change that. In a separate <a href="https://dx.doi.org/10.1038/ng.453" target="_blank" rel="noopener noreferrer">commentary in Nature Genetics</a>, Thomas O&#8217;Brien suggests that the current findings could increase the interest in developing hepatitis therapies based on the protein encoded by IL28B, interferon-Î»3.   He notes that an early clinical trial testing the effects of a related protein, interferon-Î»1, has already had some success.   And certain properties of interferon-Î»s may cause them to have fewer side effects than current treatments.
O&#8217;Brien is still cautious about the findings linking IL28B variations to hepatitis C treatment response.   He says that more research in this area is needed in diverse populations and in people infected with different forms of hepatitis C.   He also stresses that researchers need to consider how these genetic findings fit in with other factors that affect treatment response, including age and gender.
Overall, however, his view is optimistic.   He concludes: &#8220;With these caveats, predictive models of HCV treatment response hold the potential to inform treatment decisions for millions of patients who are infected with HCV.&#8221;
Map: <a href="https://en.wikipedia.org/wiki/File:HCV_prevalence_1999.png" target="_blank" rel="noopener noreferrer">PhilippN</a>

More Evidence That Genetic Variations are Important for Hepatitis C Infection and Treatment

<img loading="lazy" decoding="async" class="alignright size-medium wp-image-4383" title="Gray1087-liver" src="https://blog-api.23andme.com/wp-content/uploads/2009/08/Gray1087-liver-300x201.png" alt="Gray1087-liver" width="300" height="201" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/08/Gray1087-liver-300x201.png 300w, https://blogcms.23andme.com/wp-content/uploads/2009/08/Gray1087-liver.png 650w" sizes="auto, (max-width: 300px) 100vw, 300px" />
New research suggests the primary genetic mutation that causes alpha-1 antritrypsin deficiency, a condition that results in liver damage and a wide variety of other problems, also affects risk for liver disorders associated with cystic fibrosis.
Cystic fibrosis is an inherited, childhood-onset disorder that causes the <a href="https://blog.23andme.com/articles/snpwatch-genetic-variation-that-reduces-immune-cell-activity-may-lessen-severity-of-lung-damage-in-cystic-fibrosis-patients/" target="_blank" rel="noopener noreferrer">lungs</a>, intestines and pancreas to become clogged with mucus, resulting in breathing and digestive problems. Between three and five percent of CF patients also experience liver disease, which leads to scarring that can block blood flow through the organ and increase blood pressure in surrounding vessels.
Liver transplants have been necessary in many of these cases, but the new genetic research may be able to help prevent them by enabling prediction and prevention of CF-associated liver disease.

A team of researchers at the University of North Carolina at Chapel Hill, led by Michael Knowles, analyzed genetic variants in five genes that have been proposed to be involved in cystic fibrosis-related liver disease. The study involved nearly 1,000 patients, both with and without liver symptoms.
The results, published last week in the <a href="http://jama.ama-assn.org/cgi/content/short/302/10/1076?rss=1" target="_blank" rel="noopener noreferrer">Journal of the American Medical Association</a>, identified one genetic variation that increases a cystic fibrosis patient’s risk of developing liver disease. Researchers found that each T at the SNP increases odds of liver disease in CF patients by 4.17 times. A T at both copies of this SNP causes <a href="http://www.chestjournal.org/content/122/5/1818.full" target="_blank" rel="noopener noreferrer">alpha-1 antitrypsin deficiency</a>.
Researchers are still searching for genetic variations associated with other complications of cystic fibrosis, including lung disease, intestinal obstruction and diabetes. Further studies on severe liver disease related to cystic fibrosis may reveal more risk factors for severe symptoms that can be detected early in life.

Rare Genetic Condition May Also Increase Risk of Severe Liver Disease in Cystic Fibrosis

<img loading="lazy" decoding="async" class="alignright wp-image-4667 size-medium" title="prostatemri" src="http://35.88.189.111/wp-content/uploads/2009/09/prostatemri-300x223.jpg" alt="" width="300" height="223" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/09/prostatemri-300x223.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2009/09/prostatemri.jpg 350w" sizes="auto, (max-width: 300px) 100vw, 300px" />This MRI of a man&#8217;s pelvis shows that his prostate is enlarged to almost three times the regular size, which may be a sign of cancer. The prostate is marked by a cross.
Prostate cancer, the most common cancer to affect men, kills 30,000 men of all ethnicities each year.
The disease is known to have a strong genetic component, and several common DNA variations have been found to affect a man&#8217;s risk of prostate cancer. However, previous research has analyzed men of only European and African ancestry, leaving the effects of these genetic variants in Asian men undetermined.
<h2>New Research</h2>
Recently, researchers analyzed Japanese men for several genetic variants previously linked to prostate cancer in European and African American populations. The study found that some of these variants also affect the risk of developing prostate cancer in Asian men.
A team from Boston and Japan led by Matthew Freedman searched for risk variants by scanning the genomes of nearly 1,350 Japanese men, including more than 300 prostate cancer patients. The results, published online last week in the Journal of the National Cancer Institute, provide evidence that five out of 23 SNPs previously associated with prostate cancer among Europeans and African Americans also impact risk in this Asian population.

Although not every one of the five SNPs had a statistically significant association on its own, the group of SNPs had an association with prostate cancer. Men who carry six or more of the 10 possible risk copies at any of the five associated SNPs (people have two copies of each SNP) had 6.22 times increased odds of developing prostate cancer than men with two or fewer risk copies. The SNPs were not linked to the progression of prostate cancer, but SNPs were associated with a younger age at diagnosis.
<h2>More Research Needed</h2>
Further research with a larger number of patients will be needed to determine how several of these SNPs may have differing effects between populations of different ancestry, suggests John Ioannidis in an accompanying editorial published in the Journal of the National Cancer Institute.
&#8220;When each SNP is analyzed separately, there are clear signs of divergent risks in Asian versus European populations,&#8221; Ioannidis wrote. Several other SNPs may also have considerably different effects in these and African American populations, so more research is needed to accurately determine an individual&#8217;s risk for prostate cancer.

Genetic Variations May Increase Risk Of Prostate Cancer In Japanese Men

Scientists are narrowing in on two regions of the human genome that could be responsible for ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig&#8217;s disease.
ALS is a neurodegenerative disorder that weakens muscles and paralyzes patients within three years of onset, and has no known cure. The available drug treatment delays progression by only three to five months.
Despite several attempts to find genetic variations associated with the sporadic form of the disease (which accounts for 95% of ALS cases), no association has been found.
A team of researchers from Netherlands, Van Es et al., analyzed the genes of nearly 20,000 people of European descent, including 5,000 ALS patients. Their results, published online this week in <a href="https://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.442.html" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, identified several genetic variations on two chromosomes suspected to affect ALS and other neurological functions.

The study revealed that each copy of the C version of &nbsp; a SNP on chromosome 19, is associated with a 1.2 times increased odds of ALS compared to having two copies of A. This SNP is found near UNC13A, a gene that may be involved in the function of motor neurons, which degenerate and die in ALS patients.
Another SNP ,located on chromosome 9, is associated with a 1.16 times increased odds of ALS. This SNP was found in a region of the genome previously associated with the rare familial (non-sporadic) version of ALS. Researchers also found an association between the disease and a third SNP located very close to .
There is increasing evidence that ALS belongs to a broader spectrum of neurodegenerative disorders, including Parkinson’s disease, so researchers speculate that genetic associations with ALS may also lead to clues about other disorders of the nervous system.

Genetic Variations May Increase Risk for ALS

<img loading="lazy" decoding="async" class="alignright size-full wp-image-4632" title="iStock_000001256085XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/09/iStock_000001256085XSmall.jpg" alt="iStock_000001256085XSmall" width="300" height="199" />
About 10,000 years ago, the prehistoric hunter-gatherers of Europe began meeting some new neighbors.
These farmers spread gradually at first, expanding from the Near East through Anatolia and the Balkans. Then agriculture exploded, reaching present-day Britain within a few thousand years. The farmers settled into houses, which soon evolved into villages, towns and eventually cities.
The archaeological record tells us that much. But what it doesn&#8217;t reveal is how agriculture spread. Did it spread like a fad, as hunter-gatherer groups saw what their neighbors were doing and imitated their ways? Or was it more of an invasion, with subsequent generations of farmers advancing across the continent and overwhelming indigenous hunter-gatherer populations as they went?
Some genetic studies suggest the former. But in the September 3 issue of <a id="rbdr" title="Science" href="http://www.sciencemag.org/cgi/content/abstract/1176869" target="_blank" rel="noopener">Science</a>, the first study to directly compare ancient DNA (aDNA) from prehistoric burials of hunter-gatherers to that their agricultural neighbors suggests migrants spread farming through Europe.
The research team, led by Barbara Bramanti of Mainz University, sequenced the mitochondrial DNA (mtDNA) of just under 50 individuals unearthed from various prehistoric burial sites across central and eastern Europe. Half the individuals came from hunter-gatherer societies, and the other half from communities based around farming. As a comparison, they also sequenced the mtDNA of nearly 500 modern Europeans from the same parts of Europe.
The authors&#8217; first task was to compare the hunter-gatherer mtDNA to that of the farmers. Upon doing so, they found both groups to be so different from each other that there is no way the two could be closely related. There was absolutely no overlap in the kinds of mtDNA lineages &#8211; known as haplogroups &#8211; between the hunter-gatherers and the farmers. This stark difference suggests the earliest farmers were not related to the hunter-gatherers, and most likely came to the region by migration.
And how do these two groups compare to the modern-day Europeans? The hunter-gatherers had little in common with modern people. Haplogroup U, the most common lineage among the hunter-gatherers, is one of the least common haplogroups among modern Europeans.
But the authors also found little to connect the farmers to modern Europeans. Other studies have pointed to a substantial genetic component from the Near East among Europeans, but the authors found many genetic differences between the two groups.
Based on these results, the authors have proposed an alternative theory. The unexplained component to the genetic make-up of modern Europeans may be explained by later migrations that post-date the skeletal remains examined here. It could have been a later expansion of farmers from the Near East, or perhaps an influx of hunter-gatherers from the west. The exact details remain unclear, but the authors are confident that, with additional DNA analysis, they can hope to unravel the increasingly complex story of the peopling of Europe.

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