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Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

TitleGenetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2015
AuthorsMozaffarian, D, Kabagambe, EK, Johnson, CO, Lemaitre, RN, Manichaikul, A, Sun, Q, Foy, M, Wang, L, Wiener, H, Irvin, MR, Rich, SS, Wu, H, Jensen, MK, Chasman, DI, Chu, AY, Fornage, M, Steffen, L, King, IB, McKnight, B, Psaty, BM, Djoussé, L, Chen, IY-D, H Y Wu, J, Siscovick, DS, Ridker, PM, Tsai, MY, Rimm, EB, Hu, FB, Arnett, DK
JournalAm J Clin Nutr
Date Published2015 Feb
KeywordsAfrican Americans, Arachidonic Acid, Asian Americans, Biomarkers, European Continental Ancestry Group, Fatty Acids, Omega-6, Gene Frequency, Genetic Association Studies, Genetic Loci, Genotyping Techniques, Humans, Phospholipids, Polymorphism, Single Nucleotide, Trans Fatty Acids
Abstract<p><b>BACKGROUND: </b>Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health.</p><p><b>OBJECTIVE: </b>The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers.</p><p><b>DESIGN: </b>We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts.</p><p><b>RESULTS: </b>Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (β = 0.0035, P = 4.90 × 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (β = 0.0053, P = 1.05 × 10(-6)) and Chinese Americans (β = 0.0028, P = 0.002) but not African Americans (β = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: β = 0.0118, P = 4.05 × 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (β-coefficient reduced by 86%), with similar reductions in Hispanic Americans and Chinese Americans.</p><p><b>CONCLUSIONS: </b>Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.</p>
Alternate JournalAm. J. Clin. Nutr.
PubMed ID25646338
PubMed Central IDPMC4307209
Grant ListHL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R00-HL095649 / HL / NHLBI NIH HHS / United States
R01 HL085710 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States