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

Authors:
Saima Afaq
Saima Afaq
Institute of Public health and Social Sciences, Khyber medical university Peshawar Pakistan
Dr
Peshawar, KPK | Pakistan
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 Traci M Bartz Lawrence F Bielak Xuan Deng Rajkumar Dorajoo Kurt K Lohman Alisa K Manning Tuomo Rankinen Albert V Smith Salman M Tajuddin Evangelos Evangelou Mariaelisa Graff Maris Alver Mathilde Boissel Jin Fang Chai Xu Chen Jasmin Divers Ilaria Gandin Chuan Gao Anuj Goel Yanick Hagemeijer Sarah E Harris Fernando P Hartwig Meian He Andrea R V R Horimoto Fang-Chi Hsu Anne U Jackson Anuradhani Kasturiratne Pirjo Komulainen Brigitte Kühnel Federica Laguzzi Joseph H Lee Jian'an Luan Leo-Pekka Lyytikäinen Nana Matoba Ilja M Nolte Maik Pietzner Muhammad Riaz M Abdullah Said Robert A Scott Tamar Sofer Alena Stančáková Fumihiko Takeuchi Bamidele O Tayo Peter J van der Most Tibor V Varga Yajuan Wang Erin B Ware Wanqing Wen Lisa R Yanek Weihua Zhang Jing Hua Zhao Najaf Amin Marzyeh Amini Dan E Arking Tin Aung Christie Ballantyne Eric Boerwinkle Ulrich Broeckel Archie Campbell Mickaël Canouil Sabanayagam Charumathi Yii-Der Ida Chen John M Connell Ulf de Faire Lisa de Las Fuentes Renée de Mutsert H Janaka de Silva Jingzhong Ding Anna F Dominiczak Qing Duan Charles B Eaton Ruben N Eppinga Jessica D Faul Virginia Fisher Terrence Forrester Oscar H Franco Yechiel Friedlander Mohsen Ghanbari Franco Giulianini Hans J Grabe Megan L Grove C Charles Gu Tamara B Harris Sami Heikkinen Chew-Kiat Heng Makoto Hirata James E Hixson Barbara V Howard M Arfan Ikram David R Jacobs Craig Johnson Jost Bruno Jonas Candace M Kammerer Tomohiro Katsuya Chiea Chuen Khor Tuomas O Kilpeläinen Woon-Puay Koh Heikki A Koistinen Ivana Kolcic Charles Kooperberg Jose E Krieger Steve B Kritchevsky Michiaki Kubo Johanna Kuusisto Timo A Lakka Carl D Langefeld Claudia Langenberg Lenore J Launer Benjamin Lehne Rozenn N Lemaitre Yize Li Jingjing Liang Jianjun Liu Kiang Liu Marie Loh Tin Louie Reedik Mägi Ani W Manichaikul Colin A McKenzie Thomas Meitinger Andres Metspalu Yuri Milaneschi Lili Milani Karen L Mohlke Thomas H Mosley Kenneth J Mukamal Mike A Nalls Matthias Nauck Christopher P Nelson Nona Sotoodehnia Jeff R O'Connell Nicholette D Palmer Raha Pazoki Nancy L Pedersen Annette Peters Patricia A Peyser Ozren Polasek Neil Poulter Leslie J Raffel Olli T Raitakari Alex P Reiner Treva K Rice Stephen S Rich Antonietta Robino Jennifer G Robinson Lynda M Rose Igor Rudan Carsten O Schmidt Pamela J Schreiner William R Scott Peter Sever Yuan Shi Stephen Sidney Mario Sims Blair H Smith Jennifer A Smith Harold Snieder John M Starr Konstantin Strauch Nicholas Tan Kent D Taylor Yik Ying Teo Yih Chung Tham André G Uitterlinden Diana van Heemst Dragana Vuckovic Melanie Waldenberger Lihua Wang Yujie Wang Zhe Wang Wen Bin Wei Christine Williams Gregory Wilson Mary K Wojczynski Jie Yao Bing Yu Caizheng Yu Jian-Min Yuan Wei Zhao Alan B Zonderman Diane M Becker Michael Boehnke Donald W Bowden John C Chambers Ian J Deary Tõnu Esko Martin Farrall Paul W Franks Barry I Freedman Philippe Froguel Paolo Gasparini Christian Gieger Bernardo L Horta Yoichiro Kamatani Norihiro Kato Jaspal S Kooner Markku Laakso Karin Leander Terho Lehtimäki Patrik K E Magnusson Brenda Penninx Alexandre C Pereira Rainer Rauramaa Nilesh J Samani James Scott Xiao-Ou Shu Pim van der Harst Lynne E Wagenknecht Ya Xing Wang Nicholas J Wareham Hugh Watkins David R Weir Ananda R Wickremasinghe Wei Zheng Paul Elliott Kari E North Claude Bouchard Michele K Evans Vilmundur Gudnason Ching-Ti Liu Yongmei Liu Bruce M Psaty Paul M Ridker Rob M van Dam Sharon L R Kardia Xiaofeng Zhu Charles N Rotimi Dennis O Mook-Kanamori Myriam Fornage Tanika N Kelly Ervin R Fox Caroline Hayward Cornelia M van Duijn E Shyong Tai Tien Yin Wong Jingmin Liu Jerome I Rotter W James Gauderman Michael A Province Patricia B Munroe Kenneth Rice Daniel I Chasman L Adrienne Cupples Dabeeru C Rao Alanna C Morrison

Am J Epidemiol 2019 Jun;188(6):1033-1054

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas.

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.

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https://academic.oup.com/aje/advance-article/doi/10.1093/aje
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545280PMC
June 2019
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References

(Supplied by CrossRef)
Discovery and refinement of loci associated with lipid levels
Global Lipids Genetics Consortium et al.
Nat Genet 2013

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