Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations
Chaojie Yang, Brian Hallmark, Jin Choul Chai, Timothy D. O’Connor, Lindsay M. Reynolds, Alexis C. Wood, Michael C. Seeds, Yii-Der Ida Chen, Lyn M. Steffen, Michael Y. Tsai, Robert C. Kaplan, Martha L. Daviglus, Lawrence J. Mandarino, Amanda M. Fretts, Rozenn N. Lemaître, Dawn K. Coletta, Sarah Blomquist, Laurel Johnstone, Chandra Tontsch, Qibin Qi, Ingo Ruczinski, Stephen S. Rich, Rasika A. Mathias, Floyd H. Chilton, Ani Manichaikul
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.