Dataset Information

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

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.

SUBMITTER: de Vries PS

PROVIDER: S-EPMC6545280 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

de Vries Paul S PS Brown Michael R MR Bentley Amy R AR Sung Yun J YJ Winkler Thomas W TW Ntalla Ioanna I Schwander Karen K Kraja Aldi T AT Guo Xiuqing X Franceschini Nora N Cheng Ching-Yu CY Sim Xueling X Vojinovic Dina D Huffman Jennifer E JE Musani Solomon K SK Li Changwei C Feitosa Mary F MF Richard Melissa A MA Noordam Raymond R Aschard Hugues H Bartz Traci M TM Bielak Lawrence F LF Deng Xuan X Dorajoo Rajkumar R Lohman Kurt K KK Manning Alisa K AK Rankinen Tuomo T Smith Albert V AV Tajuddin Salman M SM Evangelou Evangelos E Graff Mariaelisa M Alver Maris M Boissel Mathilde M Chai Jin Fang JF Chen Xu X Divers Jasmin J Gandin Ilaria I Gao Chuan C Goel Anuj A Hagemeijer Yanick Y Harris Sarah E SE Hartwig Fernando P FP He Meian M Horimoto Andrea R V R ARVR Hsu Fang-Chi FC Jackson Anne U AU Kasturiratne Anuradhani A Komulainen Pirjo P Kühnel Brigitte B Laguzzi Federica F Lee Joseph H JH Luan Jian'an J Lyytikäinen Leo-Pekka LP Matoba Nana N Nolte Ilja M IM Pietzner Maik M Riaz Muhammad M Said M Abdullah MA Scott Robert A RA Sofer Tamar T Stančáková Alena A Takeuchi Fumihiko F Tayo Bamidele O BO van der Most Peter J PJ Varga Tibor V TV Wang Yajuan Y Ware Erin B EB Wen Wanqing W Yanek Lisa R LR Zhang Weihua W Zhao Jing Hua JH Afaq Saima S Amin Najaf N Amini Marzyeh M Arking Dan E DE Aung Tin T Ballantyne Christie C Boerwinkle Eric E Broeckel Ulrich U Campbell Archie A Canouil Mickaël M Charumathi Sabanayagam S Chen Yii-Der Ida YI Connell John M JM de Faire Ulf U de Las Fuentes Lisa L de Mutsert Renée R de Silva H Janaka HJ Ding Jingzhong J Dominiczak Anna F AF Duan Qing Q Eaton Charles B CB Eppinga Ruben N RN Faul Jessica D JD Fisher Virginia V Forrester Terrence T Franco Oscar H OH Friedlander Yechiel Y Ghanbari Mohsen M Giulianini Franco F Grabe Hans J HJ Grove Megan L ML Gu C Charles CC Harris Tamara B TB Heikkinen Sami S Heng Chew-Kiat CK Hirata Makoto M Hixson James E JE Howard Barbara V BV Ikram M Arfan MA Jacobs David R DR Johnson Craig C Jonas Jost Bruno JB Kammerer Candace M CM Katsuya Tomohiro T Khor Chiea Chuen CC Kilpeläinen Tuomas O TO Koh Woon-Puay WP Koistinen Heikki A HA Kolcic Ivana I Kooperberg Charles C Krieger Jose E JE Kritchevsky Steve B SB Kubo Michiaki M Kuusisto Johanna J Lakka Timo A TA Langefeld Carl D CD Langenberg Claudia C Launer Lenore J LJ Lehne Benjamin B Lemaitre Rozenn N RN Li Yize Y Liang Jingjing J Liu Jianjun J Liu Kiang K Loh Marie M Louie Tin T Mägi Reedik R Manichaikul Ani W AW McKenzie Colin A CA Meitinger Thomas T Metspalu Andres A Milaneschi Yuri Y Milani Lili L Mohlke Karen L KL Mosley Thomas H TH Mukamal Kenneth J KJ Nalls Mike A MA Nauck Matthias M Nelson Christopher P CP Sotoodehnia Nona N O'Connell Jeff R JR Palmer Nicholette D ND Pazoki Raha R Pedersen Nancy L NL Peters Annette A Peyser Patricia A PA Polasek Ozren O Poulter Neil N Raffel Leslie J LJ Raitakari Olli T OT Reiner Alex P AP Rice Treva K TK Rich Stephen S SS Robino Antonietta A Robinson Jennifer G JG Rose Lynda M LM Rudan Igor I Schmidt Carsten O CO Schreiner Pamela J PJ Scott William R WR Sever Peter P Shi Yuan Y Sidney Stephen S Sims Mario M Smith Blair H BH Smith Jennifer A JA Snieder Harold H Starr John M JM Strauch Konstantin K Tan Nicholas N Taylor Kent D KD Teo Yik Ying YY Tham Yih Chung YC Uitterlinden André G AG van Heemst Diana D Vuckovic Dragana D Waldenberger Melanie M Wang Lihua L Wang Yujie Y Wang Zhe Z Wei Wen Bin WB Williams Christine C Wilson Gregory G Wojczynski Mary K MK Yao Jie J Yu Bing B Yu Caizheng C Yuan Jian-Min JM Zhao Wei W Zonderman Alan B AB Becker Diane M DM Boehnke Michael M Bowden Donald W DW Chambers John C JC Deary Ian J IJ Esko Tõnu T Farrall Martin M Franks Paul W PW Freedman Barry I BI Froguel Philippe P Gasparini Paolo P Gieger Christian C Horta Bernardo L BL Kamatani Yoichiro Y Kato Norihiro N Kooner Jaspal S JS Laakso Markku M Leander Karin K Lehtimäki Terho T Magnusson Patrik K E PKE Penninx Brenda B Pereira Alexandre C AC Rauramaa Rainer R Samani Nilesh J NJ Scott James J Shu Xiao-Ou XO van der Harst Pim P Wagenknecht Lynne E LE Wang Ya Xing YX Wareham Nicholas J NJ Watkins Hugh H Weir David R DR Wickremasinghe Ananda R AR Zheng Wei W Elliott Paul P North Kari E KE Bouchard Claude C Evans Michele K MK Gudnason Vilmundur V Liu Ching-Ti CT Liu Yongmei Y Psaty Bruce M BM Ridker Paul M PM van Dam Rob M RM Kardia Sharon L R SLR Zhu Xiaofeng X Rotimi Charles N CN Mook-Kanamori Dennis O DO Fornage Myriam M Kelly Tanika N TN Fox Ervin R ER Hayward Caroline C van Duijn Cornelia M CM Tai E Shyong ES Wong Tien Yin TY Liu Jingmin J Rotter Jerome I JI Gauderman W James WJ Province Michael A MA Munroe Patricia B PB Rice Kenneth K Chasman Daniel I DI Cupples L Adrienne LA Rao Dabeeru C DC Morrison Alanna C AC

American journal of epidemiology 20190601 6

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 ...[more]

PMID: 30698716

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Project description:BackgroundLittle is known about the interactions of apolipoprotein (Apo) A5 gene polymorphisms and alcohol consumption on serum lipid profiles. The present study was undertaken to detect the interactions of ApoA5-1131T>C, c.553G>T and c.457G>A polymorphisms and alcohol consumption on serum lipid levels.Methodology/principal findingsA total of 516 nondrinkers and 514 drinkers were randomly selected from our previous stratified randomized cluster samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P<0.05-0.001). The genotypic and allelic frequencies of three loci were not different between the two groups. The interactions between -1131T>C genotypes and alcohol consumption on ApoB levels (P<0.05) and the ApoA1/ApoB ratio (P<0.01), between c.553G>T genotypes and alcohol consumption on low-density lipoprotein cholesterol (LDL-C) levels (P<0.05) and the ApoA1/ApoB ratio (P<0.05), and between c.457G>A genotypes and alcohol consumption on TG levels (P<0.001) were detected by factorial regression analysis after controlling for potential confounders. Four haplotypes (T-G-G, C-G-G, T-A-G and C-G-T) had frequencies ranging from 0.06 to 0.87. Three haplotypes (C-G-G, T-A-G, and C-G-T) were significantly associated with serum lipid parameters. The -1131T>C genotypes were correlated with TG, and c.553G>T and c.457G>A genotypes were associated with HDL-C levels in nondrinkers (P<0.05 for all). For drinkers, the -1131T>C genotypes were correlated with TC, TG, LDL-C, ApoB levels and the ApoA1/ApoB ratio (P<0.01 for all); c.553G>T genotypes were correlated with TC, TG, HDL-C and LDL-C levels (P<0.05-0.01); and c.457G>A genotypes were associated with TG, LDL-C, ApoA1 and ApoB levels (P<0.05-0.01).ConclusionsThe differences in some serum lipid parameters between the drinkers and nondrinkers might partly result from different interactions of the ApoA5 gene polymorphisms and alcohol consumption.

Dataset Information

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

Publications

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

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