Pulse lineResearch With Heart Logo

Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.

TitleGenome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.
Publication TypeJournal Article
Year of Publication2014
AuthorsGuan W, Steffen BT, Lemaitre RN, H Y Wu J, Tanaka T, Manichaikul A, Foy M, Rich SS, Wang L, Nettleton JA, Tang W, Gu X, Bandinelli S, King IB, McKnight B, Psaty BM, Siscovick D, Djoussé L, Chen Y-D I, Ferrucci L, Fornage M, Mozafarrian D, Tsai MY
Secondary AuthorsSteffen LM
JournalCirc Cardiovasc Genet
Volume7
Issue3
Pagination321-331
Date Published2014 Jun
ISSN1942-3268
KeywordsAdult, Aged, Aged, 80 and over, Aging, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 6, Fatty Acid Desaturases, Fatty Acids, Omega-6, Female, Genome-Wide Association Study, Genomics, Heart Diseases, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Sequence Analysis, DNA
Abstract

BACKGROUND: Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs.

METHODS AND RESULTS: To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1×10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2×10(-15), 5.0×10(-11), 7.6×10(-65), and 2.4×10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1×10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3×10(-72), 2.6×10(-151), and 6.3×10(-140), respectively).

CONCLUSIONS: Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.

DOI10.1161/CIRCGENETICS.113.000208
Alternate JournalCirc Cardiovasc Genet
PubMed ID24823311
PubMed Central IDPMC4123862
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
U01-HG-004446 / HG / NHGRI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
HSN268200625226C / / PHS HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 HL085710 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
R01 MD009164 / MD / NIMHD NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
263 MD / MD / NIMHD NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HL085710 / HL / NHLBI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
R01-HL-084099 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
U01-HG-004424 / HG / NHGRI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
821336 / / PHS HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
R01 HL084099 / HL / NHLBI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
9164 / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
U01-HG-004729 / HG / NHGRI NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
5K01DK082729-02 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC45204 / HL / NHLBI NIH HHS / United States
K01 DK082729 / DK / NIDDK NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States