Journal
PLOS ONE
Volume 15, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0230815
Keywords
-
Categories
Funding
- National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- WHI [R21 HL123677, R56 DK104806, R01 MD012765]
- NHLBI [R01HL118305, R01HL117078, HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515, 2 R01 HL55673-12]
- NIDDK [5R01DK07568102, 5R01DK089256, K24 DK080140]
- Intramural Research Program of the National Institute on Aging, National Institutes of Health [Z01-AG000513, 09-AGN248]
- National Heart, Lung and Blood Institute of the National Institutes of Health [HL119443, HL087660, HL054464, HL054457, HL054481]
- Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- European Commission FP6 STRP grant [018947 (LSHG-CT-2006-01947)]
- European Community's Seventh Framework Programme (FP7/2007-2013)/grant by the European Commission under the programme Quality of Life and Management of the Living Resources of 5th Framework Programme [HEALTH-F4-2007-201413, QLG2-CT-2002-01254]
- ENGAGE consortium
- CMSB
- Netherlands Organisation for Scientific Research [NWORFBR 047.017.043]
- Russian Foundation for Basic Research [NWORFBR 047.017.043]
- ZonMw grant [91111025]
- National Heart, Lung and Blood Institute [N01-HC25195, N02-HL-6-4278]
- National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616]
- Doris Duke Charitable Foundation Clinical Scientist Development Award
- National Heart, Lung, and Blood Institute [HL-45670]
- National Heart, Lung, and Blood Instutute [HL043851, HL080467]
- National Cancer Institute [CA047988, UM1CA182913]
- National Heart, Lung, and Blood Institute under ARRA funding [HL099355]
- NIH [N01-AG-1-2100, 271201200022C, R01DK110113, U01HG007417, R01DK101855, R01DK107786]
- MRC University Unit Programme Grant [MC_UU_00007/10]
- Chief Scientist Office of the Scottish Government Health Directorate [CZD/16/6]
- Scottish Funding Council [HR03006]
- Wellcome Trust [104036/Z/14/Z]
- UK's Medical Research Council
- National Heart, Lung, and Blood Institute (NHLBI) [NIDDK K24 DK110550]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
- Boston Medical Center
- Andrea and Charles Bronfman Philanthropies
- Erasmus Medical Center, Rotterdam
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
- NIA Intramural Research Program
- Hjartavernd (Icelandic Heart 21 Association)
- Althingi (Icelandic Parliament)
- [75N92020D00001]
- [HHSN268201500003I]
- [N01-HC-95159]
- [75N92020D00005]
- [N01-HC-95160]
- [75N92020D00002]
- [N01-HC-95161]
- [75N92020D00003]
- [N01-HC-95162]
- [75N92020D00006]
- [N01-HC-95163]
- [75N92020D00004]
- [N01-HC-95164]
- [75N92020D00007]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-000040]
- [UL1-TR-001079]
- [UL1-TR-001420]
- [UL1-TR-001881]
- [DK063491]
- MRC [MC_UU_00007/10] Funding Source: UKRI
- Wellcome Trust [104036/Z/14/Z] Funding Source: researchfish
- NATIONAL INSTITUTE ON AGING [ZIAAG007420, ZIAAG000519] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p< 1x10(-7) (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D.
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