Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight

Jessica Tyrrell, Ville Huikari, Jennifer T. Christie, Alana Cavadino, Rachel Bakker, Marie Jo A. Brion, Frank Geller, Lavinia Paternoster, Ronny Myhre, Catherine Potter, Paul C.D. Johnson, Shah Ebrahim, Bjarke Feenstra, Anna Liisa Hartikainen, Andrew T. Hattersley, Albert Hofman, Marika Kaakinen, Lynn P. Lowe, Per Magnus, Alex McConnachieMads Melbye, Jane W.Y. Ng, Ellen A. Nohr, Chris Power, Susan M. Ring, Sylvain P. Sebert, Verena Sengpiel, H. Rob Taal, Graham C.M. Watt, Naveed Sattar, Caroline L. Relton, Bo Jacobsson, Timothy M. Frayling, Thorkild I.A. Sørensen, Jeffrey C. Murray, Debbie A. Lawlor, Craig E. Pennell, Vincent W.V. Jaddoe, Elina Hypponen, William L. Lowe, Marjo Riitta Jarvelin, George Davey Smith, Rachel M. Freathy*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

Original languageEnglish (US)
Article numberdds372
Pages (from-to)5344-5358
Number of pages15
JournalHuman molecular genetics
Volume21
Issue number24
DOIs
StatePublished - Dec 1 2012

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Nicotinic Receptors
Multigene Family
Birth Weight
Smoking
Mothers
Pregnancy
Genotype
Low Birth Weight Infant
Smoke
Alleles
Confidence Intervals
Women's Rights
Smoking Cessation
Meta-Analysis
Pregnant Women
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Tyrrell, Jessica ; Huikari, Ville ; Christie, Jennifer T. ; Cavadino, Alana ; Bakker, Rachel ; Brion, Marie Jo A. ; Geller, Frank ; Paternoster, Lavinia ; Myhre, Ronny ; Potter, Catherine ; Johnson, Paul C.D. ; Ebrahim, Shah ; Feenstra, Bjarke ; Hartikainen, Anna Liisa ; Hattersley, Andrew T. ; Hofman, Albert ; Kaakinen, Marika ; Lowe, Lynn P. ; Magnus, Per ; McConnachie, Alex ; Melbye, Mads ; Ng, Jane W.Y. ; Nohr, Ellen A. ; Power, Chris ; Ring, Susan M. ; Sebert, Sylvain P. ; Sengpiel, Verena ; Taal, H. Rob ; Watt, Graham C.M. ; Sattar, Naveed ; Relton, Caroline L. ; Jacobsson, Bo ; Frayling, Timothy M. ; Sørensen, Thorkild I.A. ; Murray, Jeffrey C. ; Lawlor, Debbie A. ; Pennell, Craig E. ; Jaddoe, Vincent W.V. ; Hypponen, Elina ; Lowe, William L. ; Jarvelin, Marjo Riitta ; Smith, George Davey ; Freathy, Rachel M. / Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight. In: Human molecular genetics. 2012 ; Vol. 21, No. 24. pp. 5344-5358.
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title = "Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight",
abstract = "Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95{\%} confidence interval (95{\%} CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95{\%} CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.",
author = "Jessica Tyrrell and Ville Huikari and Christie, {Jennifer T.} and Alana Cavadino and Rachel Bakker and Brion, {Marie Jo A.} and Frank Geller and Lavinia Paternoster and Ronny Myhre and Catherine Potter and Johnson, {Paul C.D.} and Shah Ebrahim and Bjarke Feenstra and Hartikainen, {Anna Liisa} and Hattersley, {Andrew T.} and Albert Hofman and Marika Kaakinen and Lowe, {Lynn P.} and Per Magnus and Alex McConnachie and Mads Melbye and Ng, {Jane W.Y.} and Nohr, {Ellen A.} and Chris Power and Ring, {Susan M.} and Sebert, {Sylvain P.} and Verena Sengpiel and Taal, {H. Rob} and Watt, {Graham C.M.} and Naveed Sattar and Relton, {Caroline L.} and Bo Jacobsson and Frayling, {Timothy M.} and S{\o}rensen, {Thorkild I.A.} and Murray, {Jeffrey C.} and Lawlor, {Debbie A.} and Pennell, {Craig E.} and Jaddoe, {Vincent W.V.} and Elina Hypponen and Lowe, {William L.} and Jarvelin, {Marjo Riitta} and Smith, {George Davey} and Freathy, {Rachel M.}",
year = "2012",
month = "12",
day = "1",
doi = "10.1093/hmg/dds372",
language = "English (US)",
volume = "21",
pages = "5344--5358",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "24",

}

Tyrrell, J, Huikari, V, Christie, JT, Cavadino, A, Bakker, R, Brion, MJA, Geller, F, Paternoster, L, Myhre, R, Potter, C, Johnson, PCD, Ebrahim, S, Feenstra, B, Hartikainen, AL, Hattersley, AT, Hofman, A, Kaakinen, M, Lowe, LP, Magnus, P, McConnachie, A, Melbye, M, Ng, JWY, Nohr, EA, Power, C, Ring, SM, Sebert, SP, Sengpiel, V, Taal, HR, Watt, GCM, Sattar, N, Relton, CL, Jacobsson, B, Frayling, TM, Sørensen, TIA, Murray, JC, Lawlor, DA, Pennell, CE, Jaddoe, VWV, Hypponen, E, Lowe, WL, Jarvelin, MR, Smith, GD & Freathy, RM 2012, 'Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight', Human molecular genetics, vol. 21, no. 24, dds372, pp. 5344-5358. https://doi.org/10.1093/hmg/dds372

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight. / Tyrrell, Jessica; Huikari, Ville; Christie, Jennifer T.; Cavadino, Alana; Bakker, Rachel; Brion, Marie Jo A.; Geller, Frank; Paternoster, Lavinia; Myhre, Ronny; Potter, Catherine; Johnson, Paul C.D.; Ebrahim, Shah; Feenstra, Bjarke; Hartikainen, Anna Liisa; Hattersley, Andrew T.; Hofman, Albert; Kaakinen, Marika; Lowe, Lynn P.; Magnus, Per; McConnachie, Alex; Melbye, Mads; Ng, Jane W.Y.; Nohr, Ellen A.; Power, Chris; Ring, Susan M.; Sebert, Sylvain P.; Sengpiel, Verena; Taal, H. Rob; Watt, Graham C.M.; Sattar, Naveed; Relton, Caroline L.; Jacobsson, Bo; Frayling, Timothy M.; Sørensen, Thorkild I.A.; Murray, Jeffrey C.; Lawlor, Debbie A.; Pennell, Craig E.; Jaddoe, Vincent W.V.; Hypponen, Elina; Lowe, William L.; Jarvelin, Marjo Riitta; Smith, George Davey; Freathy, Rachel M.

In: Human molecular genetics, Vol. 21, No. 24, dds372, 01.12.2012, p. 5344-5358.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight

AU - Tyrrell, Jessica

AU - Huikari, Ville

AU - Christie, Jennifer T.

AU - Cavadino, Alana

AU - Bakker, Rachel

AU - Brion, Marie Jo A.

AU - Geller, Frank

AU - Paternoster, Lavinia

AU - Myhre, Ronny

AU - Potter, Catherine

AU - Johnson, Paul C.D.

AU - Ebrahim, Shah

AU - Feenstra, Bjarke

AU - Hartikainen, Anna Liisa

AU - Hattersley, Andrew T.

AU - Hofman, Albert

AU - Kaakinen, Marika

AU - Lowe, Lynn P.

AU - Magnus, Per

AU - McConnachie, Alex

AU - Melbye, Mads

AU - Ng, Jane W.Y.

AU - Nohr, Ellen A.

AU - Power, Chris

AU - Ring, Susan M.

AU - Sebert, Sylvain P.

AU - Sengpiel, Verena

AU - Taal, H. Rob

AU - Watt, Graham C.M.

AU - Sattar, Naveed

AU - Relton, Caroline L.

AU - Jacobsson, Bo

AU - Frayling, Timothy M.

AU - Sørensen, Thorkild I.A.

AU - Murray, Jeffrey C.

AU - Lawlor, Debbie A.

AU - Pennell, Craig E.

AU - Jaddoe, Vincent W.V.

AU - Hypponen, Elina

AU - Lowe, William L.

AU - Jarvelin, Marjo Riitta

AU - Smith, George Davey

AU - Freathy, Rachel M.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

AB - Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P 5 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

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U2 - 10.1093/hmg/dds372

DO - 10.1093/hmg/dds372

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