RT Journal Article
SR Electronic
T1 Methylation Analysis Reveals Fundamental Differences Between Ethnicity and Genetic Ancestry
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 036822
DO 10.1101/036822
A1 Joshua M. Galanter
A1 Christopher R. Gignoux
A1 Sam S. Oh
A1 Dara Torgerson
A1 Maria Pino-Yanes
A1 Neeta Thakur
A1 Celeste Eng
A1 Donglei Hu
A1 Scott Huntsman
A1 Harold J. Farber
A1 Pedro C Avila
A1 Emerita Brigino-Buenaventura
A1 Michael A LeNoir
A1 Kelly Meade
A1 Denise Serebrisky
A1 William Rodríguez-Cintrón
A1 Raj Kumar
A1 Jose R Rodríguez-Santana
A1 Max A. Seibold
A1 Luisa N. Borrell
A1 Esteban G. Burchard
A1 Noah Zaitlen
YR 2016
UL http://biorxiv.org/content/early/2016/01/15/036822.abstract
AB In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations.