Genome-wide association studies and fine-mapping of genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts

Authors: YANG, CHAOJE - UNIVERSITY OF VIRGINIA; VEENSTRA, JENNA - DORDT COLLEGE; BARTZ, TRACI - UNIVERSITY OF WASHINGTON; PAHL, MATTHEW - THE CHILDREN'S HOSPITAL OF PHILADELPHIA; HALLMARK, BRIAN - UNIVERSITY OF ARIZONA; CHEN, YII - HARBOR-UCLA MEDICAL CENTER; WESTRA, JASON - FATTY ACID RESEARCH INSTITUTE; STEFFEN, LYN - UNIVERSITY OF MINNESOTA; BROWN, CHRISTOPHER - UNIVERSITY OF PENNSYLVANIA; SISCOVICK, DAVID - NEW YORK ACADEMY OF MEDICINE; TSAI, MICHAEL - UNIVERSITY OF MINNESOTA; WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); RICH, STEPHEN - UNIVERSITY OF VIRGINIA; SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; O'CONNOR, TIMOTHY - UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE; MOZAFFARIAN, DARIUSH - TUFTS UNIVERSITY; GRANT, STRUAN - THE CHILDREN'S HOSPITAL OF PHILADELPHIA; CHILTON, FLOYD - UNIVERSITY OF ARIZONA; TINTLE, NATHAN - FATTY ACID RESEARCH INSTITUTE; LEMAITRE, ROZENN - UNIVERSITY OF WASHINGTON; MANICHAIKUL, ANI - UNIVERSITY OF VIRGINIA

Submitted to: Communications Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/4/2023
Publication Date: 8/16/2023
Citation: Yang, C., Veenstra, J., Bartz, T.M., Pahl, M.C., Hallmark, B., Chen, Y.D., Westra, J., Steffen, L., Brown, C.D., Siscovick, D., Tsai, M.Y., Wood, A.C., Rich, S.S., Smith, C.E., O'Connor, T.D., Mozaffarian, D., Grant, S.F., Chilton, F.H., Tintle, N.L., Lemaitre, R.N., Manichaikul, A.W. 2023. Genome-wide association studies and fine-mapping of genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts. Communications Biology. 6(1). Article 852. https://doi.org/10.1038/s42003-023-05219-w.
DOI: https://doi.org/10.1038/s42003-023-05219-w

Interpretive Summary: Omega-3 (n-3) and omega-6 (n-6) are two types of polyunsaturated fatty acids (PUFAs) found in the diet, that play critical roles in human health. We know that our genes play a role in how much of these fatty acids we have in our blood, but most of the relevant genes have been identified in individuals with European ancestry. We examined the genomes of adults with African-American ancestary, and with Hispanic/Latino ancestry, and found that some of the genes influencing these fatty acids are the same across race/ethnic groups. However, we also identified novel genes contributing to levels of these fatty acids in Hispanic/Latino adults. Our study demonstrates the value of investigating complex trait genetics in diverse ancestry populations and highlights the need for continued efforts for expanded genetic association efforts in cohorts with genetic ancestry that reflects that of the general population within the United States and worldwide.

Technical Abstract: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n=1454) and African American (n=2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P<5x10**-8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a >9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.