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...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 29, 2019
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| In: |
American journal of epidemiology
Year: 2019, Volume: 188, Issue: 6, Pages: 1033-1054 |
| ISSN: | 1476-6256 |
| DOI: | 10.1093/aje/kwz005 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1093/aje/kwz005 Verlag, Volltext: https://academic.oup.com/aje/article/188/6/1033/5304469 
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| Author Notes: | Paul S. de Vries, Michael R. Brown, Amy R. Bentley, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Karen Schwander, Aldi T. Kraja, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jennifer E. Huffman, Solomon K. Musani, Changwei Li, Mary F. Feitosa, Melissa A. Richard, Raymond Noordam, Hugues Aschard et al. |
MARC
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| 245 | 1 | 0 | |a Multiancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions |c Paul S. de Vries, Michael R. Brown, Amy R. Bentley, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Karen Schwander, Aldi T. Kraja, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jennifer E. Huffman, Solomon K. Musani, Changwei Li, Mary F. Feitosa, Melissa A. Richard, Raymond Noordam, Hugues Aschard et al. |
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| 520 | |a 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 x 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 x 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. | ||
| 650 | 4 | |a alcohol consumption | |
| 650 | 4 | |a blood-lipids | |
| 650 | 4 | |a cholesterol | |
| 650 | 4 | |a consumption | |
| 650 | 4 | |a coronary-heart-disease | |
| 650 | 4 | |a density-lipoprotein cholesterol | |
| 650 | 4 | |a gene-environment interactions | |
| 650 | 4 | |a gene-lifestyle interactions | |
| 650 | 4 | |a genome-wide association studies | |
| 650 | 4 | |a hdl cholesterol | |
| 650 | 4 | |a individuals | |
| 650 | 4 | |a lipids | |
| 650 | 4 | |a low-frequency | |
| 650 | 4 | |a metaanalysis | |
| 650 | 4 | |a plasma | |
| 650 | 4 | |a triglycerides | |
| 650 | 4 | |a vegf-b | |
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| 700 | 1 | |a Sung, Yun J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Winkler, Thomas W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ntalla, Ioanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schwander, Karen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kraja, Aldi T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Guo, Xiuqing |e VerfasserIn |4 aut | |
| 700 | 1 | |a Franceschini, Nora |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cheng, Ching-Yu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sim, Xueling |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vojinovic, Dina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huffman, Jennifer E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Musani, Solomon K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Changwei |e VerfasserIn |4 aut | |
| 700 | 1 | |a Feitosa, Mary F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Richard, Melissa A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Noordam, Raymond |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aschard, Hugues |e VerfasserIn |4 aut | |
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