Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.
Adolescent
Adult
Aged
Aged, 80 and over
Alcohol Drinking
/ genetics
Apolipoproteins E
/ genetics
Cholesterol, HDL
/ blood
Female
Gene Frequency
Genetic Loci
Genome-Wide Association Study
Humans
Lipids
/ blood
Male
Middle Aged
Polymorphism, Single Nucleotide
Proprotein Convertase 9
/ genetics
Triglycerides
/ blood
White People
/ genetics
Young Adult
exome
gene-environment interaction
genome-wide association study
lipids
self-report
Journal
Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
9
6
2020
medline:
27
10
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci ( In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
Sections du résumé
BACKGROUND
Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.
METHODS
In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered.
RESULTS
We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (
CONCLUSIONS
In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
Identifiants
pubmed: 32510982
doi: 10.1161/CIRCGEN.119.002772
pmc: PMC7442680
mid: NIHMS1603581
doi:
Substances chimiques
Apolipoproteins E
0
Cholesterol, HDL
0
Lipids
0
Triglycerides
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e002772Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135405
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL140385
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117445
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119443
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118305
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL154284
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD012765
Pays : United States
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