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Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.
Monday,2020-08-24 22:30 America/Los_Angeles — ecterry
| Title | Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Wang, Z, Chen, H, Bartz, TM, Bielak, LF, Chasman, DI, Feitosa, MF, Franceschini, N, Guo, X, Lim, E, Noordam, R, Richard, MA, Wang, H, Cade, B, Cupples, AL, de Vries, PS, Giulanini, F, Lee, J, Lemaitre, RN, Martin, LW, Reiner, AP, Rich, SS, Schreiner, PJ, Sidney, S, Sitlani, CM, Smith, JA, van Dijk, KWillems, Yao, J, Zhao, W, Fornage, M, Kardia, SLR, Kooperberg, C, Liu, C-T, Mook-Kanamori, DO, Province, MA, Psaty, BM, Redline, S, Ridker, PM, Rotter, JI, Boerwinkle, E, Morrison, AC |
| Corporate/Institutional Authors | CHARGE Gene-Lifestyle Interactions Working Group |
| Journal | Circ Genom Precis Med |
| Volume | 13 |
| Issue | 4 |
| Pagination | e002772 |
| Date Published | 2020 Aug |
| ISSN | 2574-8300 |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (, , , , , , , and ) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (=6.65×10 for the interaction test) and replicated at nominal significance level (=0.013) in .</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/CIRCGEN.119.002772 |
| Alternate Journal | Circ Genom Precis Med |
| PubMed ID | 32510982 |
| PubMed Central ID | PMC7442680 |
| Grant List | R01 DK117445 / DK / NIDDK NIH HHS / United States R01 HL118305 / HL / NHLBI NIH HHS / United States R01 MD012765 / MD / NIMHD NIH HHS / United States R21 HL140385 / HL / NHLBI NIH HHS / United States |
ePub date:
20/06