Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

• Published in: Nature genetics Vol. 51; no. 4; pp. 636 - 648
• Main Authors: Sim, Xueling, Feitosa, Mary F, Zhao, Wei, Boissel, Mathilde, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Hung, Yi-Jen, Komulainen, Pirjo, Luan, Jian'an, Nolte, Ilja M, Pietzner, Maik, Robino, Antonietta, Sofer, Tamar, Wang, Tzung-Dau, Ware, Erin B, Adeyemo, Adebowale, Afaq, Saima, Arking, Dan E, Aung, Tin, Campbell, Archie, Connell, John M, Duan, Qing, Eaton, Charles B, Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Kilpeläinen, Tuomas O, Krieger, Jose E, Kritchevsky, Stephen B, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K, Mägi, Reedik, Mahajan, Anubha, McKenzie, Colin A, Milaneschi, Yuri, Murray, Alison D, Nalls, Mike A, Nauck, Matthias, Palmer, Nicholette D, Peters, Annette, Poulter, Neil, Reiner, Alex P, Rose, Lynda M, Rudan, Igor, Scott, William R, Sever, Peter, Shi, Yuan, Sims, Mario, Tan, Nicholas Y Q, Tang, Hua, Teo, Yik Ying, Tiemeier, Henning, Uitterlinden, André G, Wang, Lan, Williams, Christine A, Yao, Jie, Young, Kristin, Zhou, Jie, Cooper, Richard S, Farrall, Martin, Freedman, Barry I, Gieger, Christian, Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kooner, Jaspal S, Laakso, Markku, Lehtimäki, Terho, Rauramaa, Rainer, Samani, Nilesh J, Shu, Xiao-Ou, van der Harst, Pim, Wang, Ya Xing, Weir, David R, Wu, Tangchun, Bouchard, Claude, Evans, Michele K, Kardia, Sharon L R, Liu, Yongmei, Fornage, Myriam, Province, Michael A, Hayward, Caroline, Rotter, Jerome I, Gauderman, W James, Munroe, Patricia B, Morrison, Alanna C, Rao, Dabeeru C, Rotimi, Charles N
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Basic Medicine; Blood lipids; Body mass index; Cardiovascular disease; Cholesterol; Diabetes; Female; Gene loci; Genes; Genetic research; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Genotype; Humans; Influence; Insulin; Life Sciences; Life Style; Lifestyles; Linkage Disequilibrium - genetics; Lipids; Lipids - blood; Lipids - genetics; Lipoproteins; Male; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Meta-analysis; Middle Aged; Novels; Population studies; Quantitative trait loci; Serum lipids; Smoking; Smoking - blood; Smoking - genetics; Studies; Triglycerides; Young Adult
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-019-0378-y

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.