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

Chaojie Yang; Jenna Veenstra; Traci M Bartz; Matthew C Pahl; Brian Hallmark; Yii-Der Ida Chen; Jason Westra; Lyn M Steffen; Christopher D Brown; David Siscovick; Michael Y Tsai; Alexis C Wood; Stephen S Rich; Caren E Smith; Timothy D O'Connor; Dariush Mozaffarian; Struan F A Grant; Floyd H Chilton; Nathan L Tintle; Rozenn N Lemaitre; Ani Manichaikul

doi:10.1038/s42003-023-05219-w

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

Commun Biol. 2023 Aug 16;6(1):852. doi: 10.1038/s42003-023-05219-w.

Authors

Chaojie Yang^{1

2}, Jenna Veenstra³, Traci M Bartz^{4

5}, Matthew C Pahl^{6

7}, Brian Hallmark⁸, Yii-Der Ida Chen⁹, Jason Westra¹⁰, Lyn M Steffen¹¹, Christopher D Brown^{12

13}, David Siscovick¹⁴, Michael Y Tsai¹⁵, Alexis C Wood¹⁶, Stephen S Rich¹, Caren E Smith¹⁷, Timothy D O'Connor¹⁸, Dariush Mozaffarian¹⁹, Struan F A Grant^{6

7

12

20

21}, Floyd H Chilton²², Nathan L Tintle^{10

23}, Rozenn N Lemaitre⁵, Ani Manichaikul²⁴

Affiliations

¹ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
² Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
³ Departments of Biology and Statistics, Dordt University, Sioux Center, IA, USA.
⁴ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
⁷ Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁸ Center for Biomedical Informatics and Biostatistics, University of Arizona, Tucson, AZ, USA.
⁹ Institute for Translational Genomics and Population Sciences and Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁰ Fatty Acid Research Institute, Sioux Falls, SD, USA.
¹¹ Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
¹² Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹³ Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ New York Academy of Medicine, New York, NY, USA.
¹⁵ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
¹⁶ USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
¹⁷ Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
¹⁸ Institute for Genome Sciences; Program in Personalized and Genomic Medicine; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁹ Friedman School of Nutrition Science & Policy, Tufts University, Tufts School of Medicine and Division of Cardiology, Tufts Medical Center, Boston, MA, USA.
²⁰ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²¹ Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
²² School of Nutritional Sciences and Wellness and the BIO5 Institute, University of Arizona, Tucson, AZ, USA.
²³ University of Illinois, Chicago, Chicago, IL, USA.
²⁴ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA. amanicha@virginia.edu.

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 < 5 × 10^-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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Bestrophins
Black or African American / genetics
Fatty Acids, Omega-6*
Genome-Wide Association Study*
Genomics
Hispanic or Latino / genetics
Humans

Substances

Fatty Acids, Omega-6
BEST1 protein, human
Bestrophins

Abstract

Publication types

MeSH terms

Substances

Grants and funding