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Pleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables.

TitlePleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables.
Publication TypeJournal Article
Year of Publication2018
AuthorsWeng L-C, Guan W, Steffen LM, Pankow JS, Pankratz N, Chen M-H, Cushman M, Basu S, Folsom AR
Secondary AuthorsTang W
JournalThromb Res
Volume168
Pagination53-59
Date Published2018 08
ISSN1879-2472
KeywordsFatty Acids, Omega-3, Fatty Acids, Unsaturated, Female, Genetic Pleiotropy, Genetic Variation, Hemostatics, Humans, Male, Middle Aged
Abstract

INTRODUCTION: Data from epidemiological studies and clinical trials suggest an influence of dietary and circulating polyunsaturated fatty acids (PUFAs) on the hemostasis profile. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) related to plasma PUFAs levels. We aimed to investigate whether the SNPs related to plasma PUFAs levels were also associated with plasma levels of hemostatic variables.

MATERIALS AND METHODS: We tested the associations between 9 PUFA-related SNPs and 6 hemostatic variables in 9035 European Americans (EAs) and 2702 African Americans (AAs) in the Atherosclerosis Risk in Communities (ARIC) Study. We then conducted a replication study by looking-up our novel observed associations in three published GWAS for hemostatic factors in different EA populations.

RESULTS: We observed a novel linoleic acid-related locus at the JMJD1C region associated with factor VII activity (FVIIc): rs10740118 and rs1935, Beta (p) = -1.31 (1 × 10) and 1.37 (5 × 10) in EAs, respectively, and - 1.24 (5 × 10) and 1.28 (3 × 10) in meta-analysis of EAs and AAs of ARIC. This novel association was replicated in two of three independent EA populations (p = 0.01 and 0.03 in meta-analyses). We confirmed previously reported associations at the docosapentaenoic acid-related GCKR locus with protein C and FVIIc and at JMJD1C with fibrinogen. Adjustment for plasma PUFAs did not abolish the associations between these loci and hemostatic variables.

CONCLUSIONS: Our study identified a novel association for FVIIc at JMJD1C, a histone demethylase that plays a role in DNA repair and possibly transcription regulation and RNA processing.

DOI10.1016/j.thromres.2018.05.032
Alternate JournalThromb Res
PubMed ID29902632
PubMed Central IDPMC6089352
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
N01 HC065226 / HC / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States