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

Abstract

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.

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Fig. 1: Study overview.
Fig. 2: Interaction of rs12740061 (LOC105378783) and current smoking status (1df).
Fig. 3: Associations observed primarily in one smoking stratum.
Fig. 4: Forest plots of select associations.

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Data availability

All summary results will be made available in dbGaP (phs000930.v7.p1).

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Acknowledgements

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Human Genome Research Institute; the National Institutes of Health; or the US Department of Health and Human Services. This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). Additional and study-specific acknowledgments appear in the Supplementary Note.

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