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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; Åsvold, Bjørn Olav; Gabrielsen, Maiken E; Campbell, Archie; Marioni, Riccardo; Kumari, Meena; Hällfors, Jenni; Männistö, Satu; Marques-Vidal, Pedro; Kaakinen, Marika; Cavadino, Alana; Postmus, Iris; Husemoen, Lise Lotte N; Skaaby, Tea; Ahluwalia, Tarun Veer Singh; Treur, Jorien L; Willemsen, Gonneke; Dale, Caroline; Wannamethee, S Goya; Lahti, Jari; Palotie, Aarno; Räikkönen, Katri; Kisialiou, Aliaksei; McConnachie, Alex; Padmanabhan, Sandosh; Wong, Andrew; Dalgård, Christine; Paternoster, Lavinia; Ben-Shlomo, Yoav; Tyrrell, Jessica; Horwood, John; Fergusson, David M; Kennedy, Martin A; Frayling, Tim; Nohr, Ellen A; Christiansen, Lene; Ohm Kyvik, Kirsten; Kuh, Diana; Watt, Graham; Eriksson, Johan; Whincup, Peter H; Vink, Jacqueline M; Boomsma, Dorret I; Davey Smith, George; Lawlor, Debbie; Linneberg, Allan; Ford, Ian; Jukema, J Wouter; Power, Christine; Hyppönen, Elina; Jarvelin, Marjo-Riitta; Preisig, Martin; Borodulin, Katja; Kaprio, Jaakko; Kivimaki, Mika; Smith, Blair H; Hayward, Caroline; Romundstad, Pål R; Sørensen, Thorkild I A; Munafò, Marcus R; Sattar, Naveed.
In:
P L o S Genetics, Vol. 10, No. 12, e1004799, 12.2014, p. 1-6.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Taylor, AE, Morris, RW, Fluharty, ME, Bjorngaard, JH, Åsvold, BO, Gabrielsen, ME, Campbell, A, Marioni, R, Kumari, M, Hällfors, J, Männistö, S, Marques-Vidal, P, Kaakinen, M, Cavadino, A, Postmus, I, Husemoen, LLN, Skaaby, T
, Ahluwalia, TVS, Treur, JL, Willemsen, G, Dale, C, Wannamethee, SG, Lahti, J, Palotie, A, Räikkönen, K, Kisialiou, A, McConnachie, A, Padmanabhan, S, Wong, A, Dalgård, C, Paternoster, L, Ben-Shlomo, Y, Tyrrell, J, Horwood, J, Fergusson, DM, Kennedy, MA, Frayling, T, Nohr, EA, Christiansen, L, Ohm Kyvik, K, Kuh, D, Watt, G, Eriksson, J, Whincup, PH, Vink, JM, Boomsma, DI, Davey Smith, G, Lawlor, D
, Linneberg, A, Ford, I, Jukema, JW, Power, C, Hyppönen, E, Jarvelin, M-R, Preisig, M, Borodulin, K, Kaprio, J, Kivimaki, M, Smith, BH, Hayward, C, Romundstad, PR
, Sørensen, TIA, Munafò, MR & Sattar, N 2014, '
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers',
P L o S Genetics, vol. 10, no. 12, e1004799, pp. 1-6.
https://doi.org/10.1371/journal.pgen.1004799APA
Taylor, A. E., Morris, R. W., Fluharty, M. E., Bjorngaard, J. H., Åsvold, B. O., Gabrielsen, M. E., Campbell, A., Marioni, R., Kumari, M., Hällfors, J., Männistö, S., Marques-Vidal, P., Kaakinen, M., Cavadino, A., Postmus, I., Husemoen, L. L. N., Skaaby, T.
, Ahluwalia, T. V. S., Treur, J. L., ... Sattar, N. (2014).
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
P L o S Genetics,
10(12), 1-6. [e1004799].
https://doi.org/10.1371/journal.pgen.1004799Vancouver
Taylor AE, Morris RW, Fluharty ME, Bjorngaard JH, Åsvold BO, Gabrielsen ME et al.
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
P L o S Genetics. 2014 Dec;10(12):1-6. e1004799.
https://doi.org/10.1371/journal.pgen.1004799Author
Taylor, Amy E ; Morris, Richard W ; Fluharty, Meg E ; Bjorngaard, Johan H ; Åsvold, Bjørn Olav ; Gabrielsen, Maiken E ; Campbell, Archie ; Marioni, Riccardo ; Kumari, Meena ; Hällfors, Jenni ; Männistö, Satu ; Marques-Vidal, Pedro ; Kaakinen, Marika ; Cavadino, Alana ; Postmus, Iris ; Husemoen, Lise Lotte N ; Skaaby, Tea ; Ahluwalia, Tarun Veer Singh ; Treur, Jorien L ; Willemsen, Gonneke ; Dale, Caroline ; Wannamethee, S Goya ; Lahti, Jari ; Palotie, Aarno ; Räikkönen, Katri ; Kisialiou, Aliaksei ; McConnachie, Alex ; Padmanabhan, Sandosh ; Wong, Andrew ; Dalgård, Christine ; Paternoster, Lavinia ; Ben-Shlomo, Yoav ; Tyrrell, Jessica ; Horwood, John ; Fergusson, David M ; Kennedy, Martin A ; Frayling, Tim ; Nohr, Ellen A ; Christiansen, Lene ; Ohm Kyvik, Kirsten ; Kuh, Diana ; Watt, Graham ; Eriksson, Johan ; Whincup, Peter H ; Vink, Jacqueline M ; Boomsma, Dorret I ; Davey Smith, George ; Lawlor, Debbie ; Linneberg, Allan ; Ford, Ian ; Jukema, J Wouter ; Power, Christine ; Hyppönen, Elina ; Jarvelin, Marjo-Riitta ; Preisig, Martin ; Borodulin, Katja ; Kaprio, Jaakko ; Kivimaki, Mika ; Smith, Blair H ; Hayward, Caroline ; Romundstad, Pål R ; Sørensen, Thorkild I A ; Munafò, Marcus R ; Sattar, Naveed. / Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. In: P L o S Genetics. 2014 ; Vol. 10, No. 12. pp. 1-6.
Bibtex
@article{888dc19357e04281b8bc10442b075571,
title = "Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers",
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.",
author = "Taylor, {Amy E} and Morris, {Richard W} and Fluharty, {Meg E} and Bjorngaard, {Johan H} and {\AA}svold, {Bj{\o}rn Olav} and Gabrielsen, {Maiken E} and Archie Campbell and Riccardo Marioni and Meena Kumari and Jenni H{\"a}llfors and Satu M{\"a}nnist{\"o} and Pedro Marques-Vidal and Marika Kaakinen and Alana Cavadino and Iris Postmus and Husemoen, {Lise Lotte N} and Tea Skaaby and Ahluwalia, {Tarun Veer Singh} and Treur, {Jorien L} and Gonneke Willemsen and Caroline Dale and Wannamethee, {S Goya} and Jari Lahti and Aarno Palotie and Katri R{\"a}ikk{\"o}nen and Aliaksei Kisialiou and Alex McConnachie and Sandosh Padmanabhan and Andrew Wong and Christine Dalg{\aa}rd and Lavinia Paternoster and Yoav Ben-Shlomo and Jessica Tyrrell and John Horwood and Fergusson, {David M} and Kennedy, {Martin A} and Tim Frayling and Nohr, {Ellen A} and Lene Christiansen and {Ohm Kyvik}, Kirsten and Diana Kuh and Graham Watt and Johan Eriksson and Whincup, {Peter H} and Vink, {Jacqueline M} and Boomsma, {Dorret I} and {Davey Smith}, George and Debbie Lawlor and Allan Linneberg and Ian Ford and Jukema, {J Wouter} and Christine Power and Elina Hypp{\"o}nen and Marjo-Riitta Jarvelin and Martin Preisig and Katja Borodulin and Jaakko Kaprio and Mika Kivimaki and Smith, {Blair H} and Caroline Hayward and Romundstad, {P{\aa}l R} and S{\o}rensen, {Thorkild I A} and Munaf{\`o}, {Marcus R} and Naveed Sattar",
year = "2014",
month = dec,
doi = "10.1371/journal.pgen.1004799",
language = "English",
volume = "10",
pages = "1--6",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "12",
}
RIS
TY - JOUR
T1 - Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers
AU - Taylor, Amy E
AU - Morris, Richard W
AU - Fluharty, Meg E
AU - Bjorngaard, Johan H
AU - Åsvold, Bjørn Olav
AU - Gabrielsen, Maiken E
AU - Campbell, Archie
AU - Marioni, Riccardo
AU - Kumari, Meena
AU - Hällfors, Jenni
AU - Männistö, Satu
AU - Marques-Vidal, Pedro
AU - Kaakinen, Marika
AU - Cavadino, Alana
AU - Postmus, Iris
AU - Husemoen, Lise Lotte N
AU - Skaaby, Tea
AU - Ahluwalia, Tarun Veer Singh
AU - Treur, Jorien L
AU - Willemsen, Gonneke
AU - Dale, Caroline
AU - Wannamethee, S Goya
AU - Lahti, Jari
AU - Palotie, Aarno
AU - Räikkönen, Katri
AU - Kisialiou, Aliaksei
AU - McConnachie, Alex
AU - Padmanabhan, Sandosh
AU - Wong, Andrew
AU - Dalgård, Christine
AU - Paternoster, Lavinia
AU - Ben-Shlomo, Yoav
AU - Tyrrell, Jessica
AU - Horwood, John
AU - Fergusson, David M
AU - Kennedy, Martin A
AU - Frayling, Tim
AU - Nohr, Ellen A
AU - Christiansen, Lene
AU - Ohm Kyvik, Kirsten
AU - Kuh, Diana
AU - Watt, Graham
AU - Eriksson, Johan
AU - Whincup, Peter H
AU - Vink, Jacqueline M
AU - Boomsma, Dorret I
AU - Davey Smith, George
AU - Lawlor, Debbie
AU - Linneberg, Allan
AU - Ford, Ian
AU - Jukema, J Wouter
AU - Power, Christine
AU - Hyppönen, Elina
AU - Jarvelin, Marjo-Riitta
AU - Preisig, Martin
AU - Borodulin, Katja
AU - Kaprio, Jaakko
AU - Kivimaki, Mika
AU - Smith, Blair H
AU - Hayward, Caroline
AU - Romundstad, Pål R
AU - Sørensen, Thorkild I A
AU - Munafò, Marcus R
AU - Sattar, Naveed
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pgen.1004799
DO - 10.1371/journal.pgen.1004799
M3 - Journal article
C2 - 25474695
VL - 10
SP - 1
EP - 6
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 12
M1 - e1004799
ER -
