Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
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Jennifer Huffman
- Function : Author
Solomon Musani
- Function : Author
Changwei Li
- Function : Author
Melissa Richard
- Function : Author
Raymond Noordam
- Function : Author
Hugues Aschard
- Function : Author
- PersonId : 1071662
- ORCID : 0000-0002-7554-6783
- IdRef : 139628924
Traci Bartz
- Function : Author
Lawrence Bielak
- Function : Author
Xuan Deng
- Function : Author
Rajkumar Dorajoo
- Function : Author
- PersonId : 786095
- ORCID : 0000-0001-6608-2051
Kurt Lohman
- Function : Author
Alisa Manning
- Function : Author
Tuomo Rankinen
- Function : Author
Albert Smith
- Function : Author
Salman Tajuddin
- Function : Author
Evangelos Evangelou
- Function : Author
Maris Alver
- Function : Author
Xu Chen
- Function : Author
Jasmin Divers
- Function : Author
Ilaria Gandin
- Function : Author
Chuan Gao
- Function : Author
Anuj Goel
- Function : Author
Yanick Hagemeijer
- Function : Author
Sarah Harris
- Function : Author
- PersonId : 800076
- ORCID : 0000-0002-2812-1651
Fernando Hartwig
- Function : Author
Meian He
- Function : Author
Andrea Horimoto
- Function : Author
Fang-Chi Hsu
- Function : Author
Anne Jackson
- Function : Author
Anuradhani Kasturiratne
- Function : Author
Pirjo Komulainen
- Function : Author
Brigitte Kühnel
- Function : Author
Federica Laguzzi
- Function : Author
Joseph Lee
- Function : Author
Jian'An Luan
- Function : Author
Leo-Pekka Lyytikäinen
- Function : Author
Nana Matoba
- Function : Author
Ilja Nolte
- Function : Author
Maik Pietzner
- Function : Author
Muhammad Riaz
- Function : Author
M Abdullah Said
- Function : Author
Robert Scott
- Function : Author
Tamar Sofer
- Function : Author
Alena Stančáková
- Function : Author
Fumihiko Takeuchi
- Function : Author
Bamidele Tayo
- Function : Author
Peter van Der Most
- Function : Author
Tibor Varga
- Function : Author
- PersonId : 801140
- ORCID : 0000-0002-2383-699X
Erin Ware
- Function : Author
Wanqing Wen
- Function : Author
Lisa Yanek
- Function : Author
Weihua Zhang
- Function : Author
Jing Hua Zhao
- Function : Author
Saima Afaq
- Function : Author
Marzyeh Amini
- Function : Author
Dan Arking
- Function : Author
Christie Ballantyne
- Function : Author
Eric Boerwinkle
- Function : Author
Ulrich Broeckel
- Function : Author
Archie Campbell
- Function : Author
Mickaël Canouil
- Function : Author
- PersonId : 781235
- ORCID : 0000-0002-3396-4549
- IdRef : 224973177
John Connell
- Function : Author
Ulf de Faire
- Function : Author
Renée de Mutsert
- Function : Author
H Janaka de Silva
- Function : Author
Jingzhong Ding
- Function : Author
Anna Dominiczak
- Function : Author
Qing Duan
- Function : Author
Charles Eaton
- Function : Author
Ruben Eppinga
- Function : Author
Jessica Faul
- Function : Author
Virginia Fisher
- Function : Author
Terrence Forrester
- Function : Author
Yechiel Friedlander
- Function : Author
Franco Giulianini
- Function : Author
Hans Grabe
- Function : Author
Tamara Harris
- Function : Author
Sami Heikkinen
- Function : Author
Chew-Kiat Heng
- Function : Author
Makoto Hirata
- Function : Author
James Hixson
- Function : Author
Barbara Howard
- Function : Author
David Jacobs
- Function : Author
Craig Johnson
- Function : Author
Jost Bruno Jonas
- Function : Author
Candace Kammerer
- Function : Author
Tomohiro Katsuya
- Function : Author
Chiea Chuen Khor
- Function : Author
- PersonId : 794004
- ORCID : 0000-0002-1128-4729
Tuomas Kilpeläinen
- Function : Author
Heikki Koistinen
- Function : Author
Ivana Kolcic
- Function : Author
Charles Kooperberg
- Function : Author
Jose Krieger
- Function : Author
Steve Kritchevsky
- Function : Author
Michiaki Kubo
- Function : Author
Johanna Kuusisto
- Function : Author
Timo Lakka
- Function : Author
Carl Langefeld
- Function : Author
Claudia Langenberg
- Function : Author
Lenore Launer
- Function : Author
Benjamin Lehne
- Function : Author
Rozenn Lemaitre
- Function : Author
Jingjing Liang
- Function : Author
- PersonId : 801651
- ORCID : 0000-0001-9439-9320
Jianjun Liu
- Function : Author
- PersonId : 764292
- ORCID : 0000-0002-3255-3019
Kiang Liu
- Function : Author
Marie Loh
- Function : Author
Tin Louie
- Function : Author
Reedik Mägi
- Function : Author
Ani Manichaikul
- Function : Author
Colin Mckenzie
- Function : Author
Thomas Meitinger
- Function : Author
Andres Metspalu
- Function : Author
Yuri Milaneschi
- Function : Author
Lili Milani
- Function : Author
Karen Mohlke
- Function : Author
Thomas Mosley
- Function : Author
Kenneth Mukamal
- Function : Author
Mike Nalls
- Function : Author
Matthias Nauck
- Function : Author
Christopher Nelson
- Function : Author
Nona Sotoodehnia
- Function : Author
Jeff O'Connell
- Function : Author
Nicholette Palmer
- Function : Author
Raha Pazoki
- Function : Author
Nancy Pedersen
- Function : Author
Annette Peters
- Function : Author
- PersonId : 764072
- ORCID : 0000-0001-6645-0985
Patricia Peyser
- Function : Author
Ozren Polasek
- Function : Author
Neil Poulter
- Function : Author
Leslie Raffel
- Function : Author
Olli Raitakari
- Function : Author
Alex Reiner
- Function : Author
Stephen Rich
- Function : Author
Antonietta Robino
- Function : Author
Jennifer Robinson
- Function : Author
Lynda Rose
- Function : Author
Igor Rudan
- Function : Author
Carsten Schmidt
- Function : Author
Pamela Schreiner
- Function : Author
William Scott
- Function : Author
Peter Sever
- Function : Author
- PersonId : 807495
- ORCID : 0000-0003-0421-2409
Stephen Sidney
- Function : Author
Mario Sims
- Function : Author
Blair Smith
- Function : Author
Jennifer Smith
- Function : Author
Harold Snieder
- Function : Author
John Starr
- Function : Author
Konstantin Strauch
- Function : Author
Diana van Heemst
- Function : Author
Dragana Vuckovic
- Function : Author
Melanie Waldenberger
- Function : Author
Yujie Wang
- Function : Author
Wen Bin Wei
- Function : Author
Gregory Wilson
- Function : Author
Bing Yu
- Function : Author
- PersonId : 765545
- ORCID : 0000-0001-7752-592X
Caizheng Yu
- Function : Author
Jian-Min Yuan
- Function : Author
Wei Zhao
- Function : Author
Alan Zonderman
- Function : Author
Diane Becker
- Function : Author
Michael Boehnke
- Function : Author
Donald Bowden
- Function : Author
John Chambers
- Function : Author
Ian Deary
- Function : Author
Tõnu Esko
- Function : Author
Martin Farrall
- Function : Author
Paul Franks
- Function : Author
Barry Freedman
- Function : Author
Paolo Gasparini
- Function : Author
Christian Gieger
- Function : Author
Bernardo Horta
- Function : Author
Yoichiro Kamatani
- Function : Author
Norihiro Kato
- Function : Author
Jaspal Kooner
- Function : Author
Markku Laakso
- Function : Author
Karin Leander
- Function : Author
- PersonId : 773564
- ORCID : 0000-0002-1404-9222
Terho Lehtimäki
- Function : Author
Patrik Magnusson
- Function : Author
Brenda Penninx
- Function : Author
Alexandre Pereira
- Function : Author
- PersonId : 761027
- ORCID : 0000-0002-7243-4807
Rainer Rauramaa
- Function : Author
Nilesh Samani
- Function : Author
- PersonId : 802419
- ORCID : 0000-0002-3286-8133
James Scott
- Function : Author
- PersonId : 766233
- ORCID : 0000-0002-2263-7024
Xiao-Ou Shu
- Function : Author
Pim van Der Harst
- Function : Author
Lynne Wagenknecht
- Function : Author
Ya Xing Wang
- Function : Author
Nicholas Wareham
- Function : Author
Hugh Watkins
- Function : Author
David Weir
- Function : Author
Ananda Wickremasinghe
- Function : Author
Wei Zheng
- Function : Author
- PersonId : 756070
- ORCID : 0000-0003-1226-070X
Paul Elliott
- Function : Author
- PersonId : 764774
- ORCID : 0000-0003-1570-3289
Claude Bouchard
- Function : Author
Michele Evans
- Function : Author
Vilmundur Gudnason
- Function : Author
Ching-Ti Liu
- Function : Author
Yongmei Liu
- Function : Author
Bruce Psaty
- Function : Author
Paul Ridker
- Function : Author
Sharon Kardia
- Function : Author
Xiaofeng Zhu
- Function : Author
Dennis Mook-Kanamori
- Function : Author
Tanika Kelly
- Function : Author
Ervin Fox
- Function : Author
Caroline Hayward
- Function : Author
Jingmin Liu
- Function : Author
W James Gauderman
- Function : Author
Kenneth Rice
- Function : Author
Daniel Chasman
- Function : Author
L Adrienne Cupples
- Function : Author
Abstract
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.