Cultural Differences May Leave Their Mark on DNA

Medical Xpress, January 10, 2017

A UC San Francisco-led study has identified signatures of ethnicity in the genome that appear to reflect an ethnic group’s shared culture and environment, rather than their common genetic ancestry.

The study examined DNA methylation—an “annotation” of DNA that alters gene expression without changing the genomic sequence itself—in a group of diverse Latino children. Methylation is one type of “epigenetic mark” that previous research has shown can be either inherited or altered by life experience. The researchers identified several hundred differences in methylation associated with either Mexican or Puerto Rican ethnicity, but discovered that only three-quarters of the epigenetic difference between the two ethnic subgroups could be accounted for by differences in the children’s genetic ancestry. The rest of the epigenetic differences, the authors suggest, may reflect a biological stamp made by the different experiences, practices, and environmental exposures distinct to the two ethnic subgroups.

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“These data suggest that the interplay between race and ethnicity as social constructs and genetic ancestry as a biological construct is more complex than we had realized,” said Noah Zaitlen, PhD, a UCSF assistant professor of medicine and co-senior author on the new study.

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“This is a big advancement of our understanding of race and ethnicity,” Burchard said. “There’s this whole debate about whether race is fundamentally genetic or is just a social construct. To our knowledge this is the first time anyone has attempted to quantify the molecular signature of the non-genetic components of race and ethnicity. It demonstrates in a whole new way that race combines both genetics and environment.”

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It’s tempting to assume that such health disparities between races and ethnicities all stem from inherited genetic differences, but that’s not necessarily the case. Different racial and ethnic groups also eat different diets, live in neighborhoods with more or less pollution, experience different levels of poverty, and are more or less likely to smoke tobacco, all of which could also impact their health outcomes.

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In the new study, the team examined methylation signatures in 573 children of self-identified Mexican or Puerto-Rican identity drawn from the GALA II study, a cohort previously developed by Burchard to study environmental and genetic components of asthma risk in Latino children. They identified 916 methylation sites that varied with ethnic identity, but found that only 520 of these differences could be completely explained by genetic ancestry—109 could be partially explained by ancestry, while 205 could not be explained by ancestry at all.

Overall, the researchers found that about 76 percent of the effect of ethnicity on DNA methylation could be accounted for by controlling for genetic ancestry, suggesting that nearly a quarter of the effect must be due to other, unknown factors. The researchers found that many of these additional methylation sites corresponded to sites that previous studies had shown to be sensitive to environmental and social factors such as maternal smoking, exposure to diesel exhaust, and psychosocial stress. This led the team to hypothesize that a large fraction of their newly disovered epigenetic markers of ethnicity likely reflect biological signatures of environmental, social, or cultural differences between ethnic subgroups.

“This suggests that using epigenetics as a biomarker could give you a lot of information about environmental exposures within particular populations that’s not captured by genetics,” Zaitlen said. “Our next step will be to understand how specific epigenetic signatures are linked to particular environmental exposures, and use those signals to understand patient risk.”

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“Like a standard family history, ethnicity is association with disease for both genetic and environmental reasons,” Zaitlen said. “If your dad or mom had a heart attack, that tells doctors a lot about your risk for a heart attack. Part of that is genetic, but part of it is that your lifestyle is influenced heavily by your parents’ lifestyle. Your ethnic group is like a much bigger family—it’s partly a matter of genetics, but it also reflects the environment of your broader community.”

 

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