Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-12-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004799 |
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| author | Amy E Taylor Richard W Morris Meg E Fluharty Johan H Bjorngaard Bjørn Olav Åsvold Maiken E Gabrielsen Archie Campbell Riccardo Marioni Meena Kumari Jenni Hällfors Satu Männistö Pedro Marques-Vidal Marika Kaakinen Alana Cavadino Iris Postmus Lise Lotte N Husemoen Tea Skaaby Tarunveer S Ahluwalia Jorien L Treur Gonneke Willemsen Caroline Dale S Goya Wannamethee Jari Lahti Aarno Palotie Katri Räikkönen Aliaksei Kisialiou Alex McConnachie Sandosh Padmanabhan Andrew Wong Christine Dalgård Lavinia Paternoster Yoav Ben-Shlomo Jessica Tyrrell John Horwood David M Fergusson Martin A Kennedy Tim Frayling Ellen A Nohr Lene Christiansen Kirsten Ohm Kyvik Diana Kuh Graham Watt Johan Eriksson Peter H Whincup Jacqueline M Vink Dorret I Boomsma George Davey Smith Debbie Lawlor Allan Linneberg Ian Ford J Wouter Jukema Christine Power Elina Hyppönen Marjo-Riitta Jarvelin Martin Preisig Katja Borodulin Jaakko Kaprio Mika Kivimaki Blair H Smith Caroline Hayward Pål R Romundstad Thorkild I A Sørensen Marcus R Munafò Naveed Sattar |
| author_facet | Amy E Taylor Richard W Morris Meg E Fluharty Johan H Bjorngaard Bjørn Olav Åsvold Maiken E Gabrielsen Archie Campbell Riccardo Marioni Meena Kumari Jenni Hällfors Satu Männistö Pedro Marques-Vidal Marika Kaakinen Alana Cavadino Iris Postmus Lise Lotte N Husemoen Tea Skaaby Tarunveer S Ahluwalia Jorien L Treur Gonneke Willemsen Caroline Dale S Goya Wannamethee Jari Lahti Aarno Palotie Katri Räikkönen Aliaksei Kisialiou Alex McConnachie Sandosh Padmanabhan Andrew Wong Christine Dalgård Lavinia Paternoster Yoav Ben-Shlomo Jessica Tyrrell John Horwood David M Fergusson Martin A Kennedy Tim Frayling Ellen A Nohr Lene Christiansen Kirsten Ohm Kyvik Diana Kuh Graham Watt Johan Eriksson Peter H Whincup Jacqueline M Vink Dorret I Boomsma George Davey Smith Debbie Lawlor Allan Linneberg Ian Ford J Wouter Jukema Christine Power Elina Hyppönen Marjo-Riitta Jarvelin Martin Preisig Katja Borodulin Jaakko Kaprio Mika Kivimaki Blair H Smith Caroline Hayward Pål R Romundstad Thorkild I A Sørensen Marcus R Munafò Naveed Sattar |
| author_sort | Amy E Taylor |
| collection | DOAJ |
| description | We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations. |
| format | Article |
| id | doaj-art-e108bc85488b45e6916607f6be734200 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e108bc85488b45e6916607f6be7342002025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-12-011012e100479910.1371/journal.pgen.1004799Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.Amy E TaylorRichard W MorrisMeg E FluhartyJohan H BjorngaardBjørn Olav ÅsvoldMaiken E GabrielsenArchie CampbellRiccardo MarioniMeena KumariJenni HällforsSatu MännistöPedro Marques-VidalMarika KaakinenAlana CavadinoIris PostmusLise Lotte N HusemoenTea SkaabyTarunveer S AhluwaliaJorien L TreurGonneke WillemsenCaroline DaleS Goya WannametheeJari LahtiAarno PalotieKatri RäikkönenAliaksei KisialiouAlex McConnachieSandosh PadmanabhanAndrew WongChristine DalgårdLavinia PaternosterYoav Ben-ShlomoJessica TyrrellJohn HorwoodDavid M FergussonMartin A KennedyTim FraylingEllen A NohrLene ChristiansenKirsten Ohm KyvikDiana KuhGraham WattJohan ErikssonPeter H WhincupJacqueline M VinkDorret I BoomsmaGeorge Davey SmithDebbie LawlorAllan LinnebergIan FordJ Wouter JukemaChristine PowerElina HyppönenMarjo-Riitta JarvelinMartin PreisigKatja BorodulinJaakko KaprioMika KivimakiBlair H SmithCaroline HaywardPål R RomundstadThorkild I A SørensenMarcus R MunafòNaveed SattarWe previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.https://doi.org/10.1371/journal.pgen.1004799 |
| spellingShingle | Amy E Taylor Richard W Morris Meg E Fluharty Johan H Bjorngaard Bjørn Olav Åsvold Maiken E Gabrielsen Archie Campbell Riccardo Marioni Meena Kumari Jenni Hällfors Satu Männistö Pedro Marques-Vidal Marika Kaakinen Alana Cavadino Iris Postmus Lise Lotte N Husemoen Tea Skaaby Tarunveer S Ahluwalia Jorien L Treur Gonneke Willemsen Caroline Dale S Goya Wannamethee Jari Lahti Aarno Palotie Katri Räikkönen Aliaksei Kisialiou Alex McConnachie Sandosh Padmanabhan Andrew Wong Christine Dalgård Lavinia Paternoster Yoav Ben-Shlomo Jessica Tyrrell John Horwood David M Fergusson Martin A Kennedy Tim Frayling Ellen A Nohr Lene Christiansen Kirsten Ohm Kyvik Diana Kuh Graham Watt Johan Eriksson Peter H Whincup Jacqueline M Vink Dorret I Boomsma George Davey Smith Debbie Lawlor Allan Linneberg Ian Ford J Wouter Jukema Christine Power Elina Hyppönen Marjo-Riitta Jarvelin Martin Preisig Katja Borodulin Jaakko Kaprio Mika Kivimaki Blair H Smith Caroline Hayward Pål R Romundstad Thorkild I A Sørensen Marcus R Munafò Naveed Sattar Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. PLoS Genetics |
| title | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. |
| title_full | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. |
| title_fullStr | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. |
| title_full_unstemmed | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. |
| title_short | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. |
| title_sort | stratification by smoking status reveals an association of chrna5 a3 b4 genotype with body mass index in never smokers |
| url | https://doi.org/10.1371/journal.pgen.1004799 |
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