Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers

Taylor, Amy E., Morris, Richard W., Fluharty, Meg E., Bjorngaard, Johan H., Asvold, Bjorn Olav, Gabrielsen, Maiken E., Campbell, Archie, Marioni, Riccardo, Kumari, Meena, Hallfors, Jenni, Mannisto, Satu, Marques-Vidal, Pedro, Kaakinen, Marika, Cavadino, Alana, Postmus, Iris, Husemoen, Lise Lotte N., Skaaby, Tea, Ahluwalia, Tarunveer S., Treur, Jorien L., Willemsen, Gonneke, Dale, Caroline, Wannamethee, S. Goya, Lahti, Jari, Palotie, Aarno, Raikkonen, Katri, Kisialiou, Aliaksei, McConnachie, Alex, Padmanabhan, Sandosh, Wong, Andrew, Dalgard, Christine, Paternoster, Lavinia, Ben-Shlomo, Yoav, Tyrrell, Jessica, Horwood, John, Fergusson, David M., Kennedy, Martin A., Frayling, Tim, Nohr, Ellen A., Christiansen, Lene, Kyvik, Kirsten Ohm, Kuh, Diana, Watt, Graham, Eriksson, Johan, Whincup, Peter H., Vink, Jacqueline M., Boomsma, Dorret I., Smith, George Davey, Lawlor, Debbie, Linneberg, Allan, Ford, Ian, Jukema, J. Wouter, Power, Christine, Hypponen, Elina, Jarvelin, Marjo-Riitta, Preisig, Martin, Borodulin, Katja, Kaprio, Jaakko, Kivimaki, Mika, Smith, Blair H., Hayward, Caroline, Romundstad, Pal R., Sorensen, Thorkild I. A., Munafo, Marcus R. and Sattar, Naveed (2014) Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. PLoS Genetics, 10 12: 1-6. doi:10.1371/journal.pgen.1004799

Author Taylor, Amy E.
Morris, Richard W.
Fluharty, Meg E.
Bjorngaard, Johan H.
Asvold, Bjorn Olav
Gabrielsen, Maiken E.
Campbell, Archie
Marioni, Riccardo
Kumari, Meena
Hallfors, Jenni
Mannisto, Satu
Marques-Vidal, Pedro
Kaakinen, Marika
Cavadino, Alana
Postmus, Iris
Husemoen, Lise Lotte N.
Skaaby, Tea
Ahluwalia, Tarunveer S.
Treur, Jorien L.
Willemsen, Gonneke
Dale, Caroline
Wannamethee, S. Goya
Lahti, Jari
Palotie, Aarno
Raikkonen, Katri
Kisialiou, Aliaksei
McConnachie, Alex
Padmanabhan, Sandosh
Wong, Andrew
Dalgard, Christine
Paternoster, Lavinia
Ben-Shlomo, Yoav
Tyrrell, Jessica
Horwood, John
Fergusson, David M.
Kennedy, Martin A.
Frayling, Tim
Nohr, Ellen A.
Christiansen, Lene
Kyvik, Kirsten Ohm
Kuh, Diana
Watt, Graham
Eriksson, Johan
Whincup, Peter H.
Vink, Jacqueline M.
Boomsma, Dorret I.
Smith, George Davey
Lawlor, Debbie
Linneberg, Allan
Ford, Ian
Jukema, J. Wouter
Power, Christine
Hypponen, Elina
Jarvelin, Marjo-Riitta
Preisig, Martin
Borodulin, Katja
Kaprio, Jaakko
Kivimaki, Mika
Smith, Blair H.
Hayward, Caroline
Romundstad, Pal R.
Sorensen, Thorkild I. A.
Munafo, Marcus R.
Sattar, Naveed
Title Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers
Formatted title
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7404
Publication date 2014-12-04
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1004799
Open Access Status DOI
Volume 10
Issue 12
Start page 1
End page 6
Total pages 6
Place of publication San Francisco CA , United States
Publisher Public Library of Science
Collection year 2015
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
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