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

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. Geneti... Mehr ...

Verfasser: de Vries, Paul S
Brown, Michael R
Bentley, Amy R
Sung, Yun J
Winkler, Thomas W
Ntalla, Ioanna
Schwander, Karen
Kraja, Aldi T
Guo, Xiuqing
Franceschini, Nora
Cheng, Ching-Yu
Sim, Xueling
Vojinovic, Dina
Huffman, Jennifer E
Musani, Solomon K
Li, Changwei
Feitosa, Mary F
Richard, Melissa A
Noordam, Raymond
Aschard, Hugues
Bartz, Traci M
Bielak, Lawrence F
Deng, Xuan
Dorajoo, Rajkumar
Lohman, Kurt K
Manning, Alisa K
Rankinen, Tuomo
Smith, Albert V
Tajuddin, Salman M
Evangelou, Evangelos
Graff, Mariaelisa
Alver, Maris
Boissel, Mathilde
Chai, Jin Fang
Chen, Xu
Divers, Jasmin
Gandin, Ilaria
Gao, Chuan
Goel, Anuj
Hagemeijer, Yanick
Harris, Sarah E
Hartwig, Fernando P
He, Meian
Horimoto, Andrea RVR
Hsu, Fang-Chi
Jackson, Anne U
Kasturiratne, Anuradhani
Komulainen, Pirjo
Kühnel, Brigitte
Laguzzi, Federica
Lee, Joseph H
Luan, Jian'an
Lyytikäinen, Leo-Pekka
Matoba, Nana
Nolte, Ilja M
Pietzner, Maik
Riaz, Muhammad
Said, M Abdullah
Scott, Robert A
Sofer, Tamar
Stančáková, Alena
Takeuchi, Fumihiko
Tayo, Bamidele O
van der Most, Peter J
Varga, Tibor V
Wang, Yajuan
Ware, Erin B
Wen, Wanqing
Yanek, Lisa R
Zhang, Weihua
Zhao, Jing Hua
Afaq, Saima
Amin, Najaf
Amini, Marzyeh
Arking, Dan E
Aung, Tin
Ballantyne, Christie
Boerwinkle, Eric
Broeckel, Ulrich
Campbell, Archie
Canouil, Mickaël
Charumathi, Sabanayagam
Chen, Yii-Der Ida
Connell, John M
de Faire, Ulf
de las Fuentes, Lisa
de Mutsert, Renée
de Silva, H Janaka
Ding, Jingzhong
Dominiczak, Anna F
Duan, Qing
Eaton, Charles B
Eppinga, Ruben N
Faul, Jessica D
Fisher, Virginia
Forrester, Terrence
Franco, Oscar H
Friedlander, Yechiel
Ghanbari, Mohsen
Giulianini, Franco
Dokumenttyp: Artikel
Erscheinungsdatum: 2019
Reihe/Periodikum: American Journal of Epidemiology, vol 188, iss 6
Verlag/Hrsg.: eScholarship
University of California
Schlagwörter: Epidemiology / Health Sciences / Substance Misuse / Alcoholism / Alcohol Use and Health / Human Genome / Prevention / Genetics / Aetiology / 2.1 Biological and endogenous factors / Cardiovascular / Adolescent / Adult / Aged / Alcohol Drinking / Cholesterol / HDL / LDL / Female / Genome-Wide Association Study / Genotype / Humans / Life Style / Lipids / Male / Middle Aged / Phenotype / Racial Groups / Triglycerides / Vascular Endothelial Growth Factor B / Young Adult / alcohol consumption / gene-environment interactions / gene-lifestyle interactions / genome-wide association studies / InterAct Consortium / Lifelines Cohort / Groningen / The Netherlands / Mathematical Sciences / Medical and Health Sciences
Sprache: unknown
Permalink: https://search.fid-benelux.de/Record/base-29158448
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://escholarship.org/uc/item/0490n58v

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 < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.