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

Research output: Contribution to journalArticle

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 × 10−3) and 1.37 (5 × 10−4) in EAs, respectively, and − 1.24 (5 × 10−4) and 1.28 (3 × 10−4) 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.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalThrombosis Research
Volume168
DOIs
StatePublished - Aug 1 2018

Fingerprint

Omega-3 Fatty Acids
Hemostatics
Unsaturated Fatty Acids
Factor VII
Single Nucleotide Polymorphism
Genome-Wide Association Study
African Americans
Meta-Analysis
Atherosclerosis
Histone Demethylases
Linoleic Acid
Protein C
Hemostasis
DNA Repair
Fibrinogen
Population
Epidemiologic Studies
Clinical Trials
RNA

Keywords

  • Genetic pleiotropy
  • Hemostatic variables
  • Polyunsaturated fatty acids
  • Single nucleotide polymorphism

Cite this

@article{a0c17a59756a44e0beb812c83e30ae60,
title = "Pleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables",
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 × 10−3) and 1.37 (5 × 10−4) in EAs, respectively, and − 1.24 (5 × 10−4) and 1.28 (3 × 10−4) 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.",
keywords = "Genetic pleiotropy, Hemostatic variables, Polyunsaturated fatty acids, Single nucleotide polymorphism",
author = "Weng, {Lu Chen} and Weihua Guan and Steffen, {Lyn M} and Jim Pankow and Pankratz, {Nathan D} and Chen, {Ming Huei} and Mary Cushman and Saonli Basu and Folsom, {Aaron R} and Weihong Tang",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.thromres.2018.05.032",
language = "English (US)",
volume = "168",
pages = "53--59",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Pleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables

AU - Weng, Lu Chen

AU - Guan, Weihua

AU - Steffen, Lyn M

AU - Pankow, Jim

AU - Pankratz, Nathan D

AU - Chen, Ming Huei

AU - Cushman, Mary

AU - Basu, Saonli

AU - Folsom, Aaron R

AU - Tang, Weihong

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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 × 10−3) and 1.37 (5 × 10−4) in EAs, respectively, and − 1.24 (5 × 10−4) and 1.28 (3 × 10−4) 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.

AB - 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 × 10−3) and 1.37 (5 × 10−4) in EAs, respectively, and − 1.24 (5 × 10−4) and 1.28 (3 × 10−4) 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.

KW - Genetic pleiotropy

KW - Hemostatic variables

KW - Polyunsaturated fatty acids

KW - Single nucleotide polymorphism

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U2 - 10.1016/j.thromres.2018.05.032

DO - 10.1016/j.thromres.2018.05.032

M3 - Article

VL - 168

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EP - 59

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

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