Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose.
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 b...
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2020
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oai:doaj.org-article:2b6f95449b6b4935b0d4624e65bfbe832021-12-02T20:05:47ZSmoking-by-genotype interaction in type 2 diabetes risk and fasting glucose.1932-620310.1371/journal.pone.0230815https://doaj.org/article/2b6f95449b6b4935b0d4624e65bfbe832020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0230815https://doaj.org/toc/1932-6203Smoking 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.Peitao WuDenis RybinLawrence F BielakMary F FeitosaNora FranceschiniYize LiYingchang LuJonathan MartenSolomon K MusaniRaymond NoordamSridharan RaghavanLynda M RoseKaren SchwanderAlbert V SmithSalman M TajuddinDina VojinovicNajaf AminDonna K ArnettErwin P BottingerAyse DemirkanJose C FlorezMohsen GhanbariTamara B HarrisLenore J LaunerJingmin LiuJun LiuDennis O Mook-KanamoriAlison D MurrayMike A NallsPatricia A PeyserAndré G UitterlindenTrudy VoortmanClaude BouchardDaniel ChasmanAdolfo CorreaRenée de MutsertMichele K EvansVilmundur GudnasonCaroline HaywardLinda KaoSharon L R KardiaCharles KooperbergRuth J F LoosMichael M ProvinceTuomo RankinenSusan RedlinePaul M RidkerJerome I RotterDavid SiscovickBlair H SmithCornelia van DuijnAlan B ZondermanD C RaoJames G WilsonJosée DupuisJames B MeigsChing-Ti LiuJason L VassyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 5, p e0230815 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Peitao Wu Denis Rybin Lawrence F Bielak Mary F Feitosa Nora Franceschini Yize Li Yingchang Lu Jonathan Marten Solomon K Musani Raymond Noordam Sridharan Raghavan Lynda M Rose Karen Schwander Albert V Smith Salman M Tajuddin Dina Vojinovic Najaf Amin Donna K Arnett Erwin P Bottinger Ayse Demirkan Jose C Florez Mohsen Ghanbari Tamara B Harris Lenore J Launer Jingmin Liu Jun Liu Dennis O Mook-Kanamori Alison D Murray Mike A Nalls Patricia A Peyser André G Uitterlinden Trudy Voortman Claude Bouchard Daniel Chasman Adolfo Correa Renée de Mutsert Michele K Evans Vilmundur Gudnason Caroline Hayward Linda Kao Sharon L R Kardia Charles Kooperberg Ruth J F Loos Michael M Province Tuomo Rankinen Susan Redline Paul M Ridker Jerome I Rotter David Siscovick Blair H Smith Cornelia van Duijn Alan B Zonderman D C Rao James G Wilson Josée Dupuis James B Meigs Ching-Ti Liu Jason L Vassy Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| description |
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. |
| format |
article |
| author |
Peitao Wu Denis Rybin Lawrence F Bielak Mary F Feitosa Nora Franceschini Yize Li Yingchang Lu Jonathan Marten Solomon K Musani Raymond Noordam Sridharan Raghavan Lynda M Rose Karen Schwander Albert V Smith Salman M Tajuddin Dina Vojinovic Najaf Amin Donna K Arnett Erwin P Bottinger Ayse Demirkan Jose C Florez Mohsen Ghanbari Tamara B Harris Lenore J Launer Jingmin Liu Jun Liu Dennis O Mook-Kanamori Alison D Murray Mike A Nalls Patricia A Peyser André G Uitterlinden Trudy Voortman Claude Bouchard Daniel Chasman Adolfo Correa Renée de Mutsert Michele K Evans Vilmundur Gudnason Caroline Hayward Linda Kao Sharon L R Kardia Charles Kooperberg Ruth J F Loos Michael M Province Tuomo Rankinen Susan Redline Paul M Ridker Jerome I Rotter David Siscovick Blair H Smith Cornelia van Duijn Alan B Zonderman D C Rao James G Wilson Josée Dupuis James B Meigs Ching-Ti Liu Jason L Vassy |
| author_facet |
Peitao Wu Denis Rybin Lawrence F Bielak Mary F Feitosa Nora Franceschini Yize Li Yingchang Lu Jonathan Marten Solomon K Musani Raymond Noordam Sridharan Raghavan Lynda M Rose Karen Schwander Albert V Smith Salman M Tajuddin Dina Vojinovic Najaf Amin Donna K Arnett Erwin P Bottinger Ayse Demirkan Jose C Florez Mohsen Ghanbari Tamara B Harris Lenore J Launer Jingmin Liu Jun Liu Dennis O Mook-Kanamori Alison D Murray Mike A Nalls Patricia A Peyser André G Uitterlinden Trudy Voortman Claude Bouchard Daniel Chasman Adolfo Correa Renée de Mutsert Michele K Evans Vilmundur Gudnason Caroline Hayward Linda Kao Sharon L R Kardia Charles Kooperberg Ruth J F Loos Michael M Province Tuomo Rankinen Susan Redline Paul M Ridker Jerome I Rotter David Siscovick Blair H Smith Cornelia van Duijn Alan B Zonderman D C Rao James G Wilson Josée Dupuis James B Meigs Ching-Ti Liu Jason L Vassy |
| author_sort |
Peitao Wu |
| title |
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| title_short |
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| title_full |
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| title_fullStr |
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| title_full_unstemmed |
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| title_sort |
smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2020 |
| url |
https://doaj.org/article/2b6f95449b6b4935b0d4624e65bfbe83 |
| work_keys_str_mv |
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