Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. / 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 R V R; Hsu, Fang-Chi; Jackson, Anne U; Kasturiratne, Anuradhani; Komulainen, Pirjo; Zhao, Jing Hua; Kilpeläinen, Tuomas O; InterAct Consortium ; V Varga, Tibor.
In: American Journal of Epidemiology, Vol. 188, No. 6, 2019, p. 1033-1054.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
AU - de Vries, Paul S
AU - Brown, Michael R
AU - Bentley, Amy R
AU - Sung, Yun J
AU - Winkler, Thomas W
AU - Ntalla, Ioanna
AU - Schwander, Karen
AU - Kraja, Aldi T
AU - Guo, Xiuqing
AU - Franceschini, Nora
AU - Cheng, Ching-Yu
AU - Sim, Xueling
AU - Vojinovic, Dina
AU - Huffman, Jennifer E
AU - Musani, Solomon K
AU - Li, Changwei
AU - Feitosa, Mary F
AU - Richard, Melissa A
AU - Noordam, Raymond
AU - Aschard, Hugues
AU - Bartz, Traci M
AU - Bielak, Lawrence F
AU - Deng, Xuan
AU - Dorajoo, Rajkumar
AU - Lohman, Kurt K
AU - Manning, Alisa K
AU - Rankinen, Tuomo
AU - Smith, Albert V
AU - Tajuddin, Salman M
AU - Evangelou, Evangelos
AU - Graff, Mariaelisa
AU - Alver, Maris
AU - Boissel, Mathilde
AU - Chai, Jin Fang
AU - Chen, Xu
AU - Divers, Jasmin
AU - Gandin, Ilaria
AU - Gao, Chuan
AU - Goel, Anuj
AU - Hagemeijer, Yanick
AU - Harris, Sarah E
AU - Hartwig, Fernando P
AU - He, Meian
AU - Horimoto, Andrea R V R
AU - Hsu, Fang-Chi
AU - Jackson, Anne U
AU - Kasturiratne, Anuradhani
AU - Komulainen, Pirjo
AU - Zhao, Jing Hua
AU - Kilpeläinen, Tuomas O
AU - InterAct Consortium
AU - V Varga, Tibor
PY - 2019
Y1 - 2019
N2 - An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
AB - An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
U2 - 10.1093/aje/kwz005
DO - 10.1093/aje/kwz005
M3 - Journal article
C2 - 30698716
VL - 188
SP - 1033
EP - 1054
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
SN - 0002-9262
IS - 6
ER -
ID: 213240324