Pulse lineResearch With Heart Logo

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

TitleMultiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
Publication TypeJournal Article
Year of Publication2019
Authorsde Vries PS, Brown MR, Bentley AR, et al.
Secondary AuthorsMorrison AC
Corporate AuthorsInterAct Consortium, Lifelines Cohort, Groningen, The Netherlands(Lifelines Cohort Study)
JournalAm J Epidemiol
Volume188
Issue6
Pagination1033-1054
Date Published2019 06 01
ISSN1476-6256
KeywordsAdolescent, Adult, Aged, Alcohol Drinking, Cholesterol, HDL, Cholesterol, LDL, Continental Population Groups, Female, Genome-Wide Association Study, Genotype, Humans, Life Style, Lipids, Male, Middle Aged, Phenotype, Triglycerides, Vascular Endothelial Growth Factor B, Young Adult
Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P

DOI10.1093/aje/kwz005
Alternate JournalAm J Epidemiol
PubMed ID30698716
PubMed Central IDPMC6545280
Grant ListR01 DK093757 / DK / NIDDK NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
U10 HL054472 / HL / NHLBI NIH HHS / United States
U01 HL054472 / HL / NHLBI NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
R01 HL071025 / HL / NHLBI NIH HHS / United States
U01 HL054471 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U01 HL054496 / HL / NHLBI NIH HHS / United States
U10 HL054497 / HL / NHLBI NIH HHS / United States
R01 HL053353 / HL / NHLBI NIH HHS / United States
R01 DK085175 / DK / NIDDK NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
Z01 AG000513 / ImNIH / Intramural NIH HHS / United States
ZIA HG000024 / ImNIH / Intramural NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
HHSN268201300026C / HL / NHLBI NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R56 DK062370 / DK / NIDDK NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
MR/K002414/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087698 / HL / NHLBI NIH HHS / United States
R01 HL071917 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
R03 AG046389 / AG / NIA NIH HHS / United States
U10 HL054509 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
BHF/RG/2000004 / BHF_ / British Heart Foundation / United Kingdom
U01 AG009740 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
SP/04/002 / BHF_ / British Heart Foundation / United Kingdom
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
Z01 HG200362 / ImNIH / Intramural NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
PG/02/128 / BHF_ / British Heart Foundation / United Kingdom
R01 HL043851 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
U10 HL054464 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
G0700931 / MRC_ / Medical Research Council / United Kingdom
U01 HL054497 / HL / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
U01 HL054509 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
MR/L01632X/1 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL142302 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
R01 CA144034 / CA / NCI NIH HHS / United States
ZIA EY000401 / ImNIH / Intramural NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
MC_UP_1605/7 / MRC_ / Medical Research Council / United Kingdom
R01 HL087652 / HL / NHLBI NIH HHS / United States
UM1 CA173640 / CA / NCI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
K23 HL105897 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
HHSN268201300025C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
MR/L01341X/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL060944 / HL / NHLBI NIH HHS / United States
G0601966 / MRC_ / Medical Research Council / United Kingdom
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
U01 HL054464 / HL / NHLBI NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL119443 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 HL118305 / HL / NHLBI NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
R01 DK062370 / DK / NIDDK NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL067348 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
U01 HL047902 / HL / NHLBI NIH HHS / United States
U10 HL054481 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201300027C / HL / NHLBI NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201300049C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
G9521010D / MRC_ / Medical Research Council / United Kingdom
090532/Z/09 / WT_ / Wellcome Trust / United Kingdom
HHSN268200900041C / HL / NHLBI NIH HHS / United States
HHSN268201300028C / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
R01 HL061019 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
R01 LM010098 / LM / NLM NIH HHS / United States
M01 RR000052 / RR / NCRR NIH HHS / United States
RC1 HL099747 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
R01 HL049762 / HL / NHLBI NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
U01 HL072518 / HL / NHLBI NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
R01 HL088215 / HL / NHLBI NIH HHS / United States
M01 RR007122 / RR / NCRR NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
M01 RR010284 / RR / NCRR NIH HHS / United States
R01 HL059684 / HL / NHLBI NIH HHS / United States
RG/12/16/29939 / BHF_ / British Heart Foundation / United Kingdom
R01 HL087263 / HL / NHLBI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
U01 HL072507 / HL / NHLBI NIH HHS / United States
R01 DK071891 / DK / NIDDK NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
R01 HL086718 / HL / NHLBI NIH HHS / United States
U01 AG023746 / AG / NIA NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
R01 HL060919 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
U01 HL054481 / HL / NHLBI NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
U10 HL054473 / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
U10 HL054495 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
U01 CA182913 / CA / NCI NIH HHS / United States
U10 HL054496 / HL / NHLBI NIH HHS / United States
U10 HL054471 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
HHSN268201300029C / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 HL092165 / HL / NHLBI NIH HHS / United States
R01 HL090682 / HL / NHLBI NIH HHS / United States
UM1 CA182910 / CA / NCI NIH HHS / United States
MR/R026505/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL087700 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 NS062059 / NS / NINDS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
084723/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
U01 HL054495 / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
R01 HL092301 / HL / NHLBI NIH HHS / United States
U01 HL054473 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
UM1 CA182876 / CA / NCI NIH HHS / United States
R01 HL045670 / HL / NHLBI NIH HHS / United States