Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

Authors: YANG, CHAOJIE - University Of Virginia; HALLMARK, BRIAN - University Of Arizona; CHAI, JIN - Albert Einstein College Of Medicine; O'CONNOR, TIMOTHY - University Of Maryland School Of Medicine; REYNOLDS, LINDSAY - Wake Forest School Of Medicine; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); SEEDS, MICHAEL - Wake Forest University; CHEN, YII - Harbor-Ucla Medical Center; STEFFEN, LYN - University Of Minnesota; TSAI, MICHAEL - University Of Minnesota; KAPLAN, ROBERT - Albert Einstein College Of Medicine; DAVIGLUS, MARTHA - University Of Illinois; MANDARINO, LAWRENCE - University Of Arizona; FRETTS, AMANDA - University Of Washington; LEMAITRE, ROZENN - University Of Washington; COLETTA, DAWN - University Of Arizona; BLOMQUIST, SARAH - University Of Arizona; JOHNSTONE, LAUREL - University Of Arizona; TONTSCH, CHANDRA - University Of Arizona; QI, QIBIN - Albert Einstein College Of Medicine; RUCZINSKI, INGO - Johns Hopkins University; RICH, STEPHEN - University Of Virginia; MATHIAS, RASIKA - Johns Hopkins University; CHILTON, FLOYD - University Of Arizona; MANICHAIKUL, ANI - University Of Virginia

Submitted to: Communications Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/22/2021
Publication Date: 7/28/2021
Citation: Yang, C., Hallmark, B., Chai, J.C., O'Connor, T.D., Reynolds, L.M., Wood, A.C., Seeds, M., Chen, Y.D., Steffen, L.M., Tsai, M.Y., Kaplan, R.C., Daviglus, M.L., Mandarino, L.J., Fretts, A.M., Lemaitre, R.N., Coletta, D.K., Blomquist, S.A., Johnstone, L.M., Tontsch, C., Qi, Q., Ruczinski, I., Rich, S.S., Mathias, R.A., Chilton, F.H., Manichaikul, A. 2021. Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations. Communications Biology. 4:918. https://doi.org/10.1038/s42003-021-02431-4.
DOI: https://doi.org/10.1038/s42003-021-02431-4

Interpretive Summary: Hispanic populations have higher rates of obesity, hypertriglyceridemia, and a greater prevalence of type 2 diabetes. Long chain polyunsaturated fatty acids (LC-PUFAs) may be protective against these conditions. Genetic variation in the FADS cluster is a major reason for why some people have high levels of LC-PUFAs in their blood compared to others, and the variants associated with low levels of LC-PUFAs occur at strikingly higher frequencies in Amerind (AI) ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation, levels of LC-PUFAs in the blood, and markers of disease risk in a large population of Hispanic Americans from three different cohort studies. We found that those with AI genetic ancestry had much lower LC-PUFA levels, which was mostly attributable to a single variant in the FADS cluster of genes (rs174537). This variant was also strongly associated with triglyceride levels. These analyses imply that AI ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies which can lead to an increased risk of adverse health-related outcomes.

Technical Abstract: Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.