Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported 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 McConnachie; Mads 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; Early Growth Genetics (EGG) Consortium

doi:10.1093/hmg/dds372

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported 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, Early Growth Genetics (EGG) Consortium

48 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 language	English
Journal	Human Molecular Genetics
Volume	21
Issue number	24
Pages (from-to)	5344-58
Number of pages	15
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/dds372
Publication status	Published - Dec 2012

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Tyrrell, J., Huikari, V., Christie, J. T., Cavadino, A., Bakker, R., Brion, M-J. A., Geller, F., Paternoster, L., Myhre, R., Potter, C., Johnson, P. C. D., Ebrahim, S., Feenstra, B., Hartikainen, A-L., Hattersley, A. T., Hofman, A., Kaakinen, M., Lowe, L. P., Magnus, P., ... Early Growth Genetics (EGG) Consortium (2012). Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. Human Molecular Genetics, 21(24), 5344-58. https://doi.org/10.1093/hmg/dds372

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. / Tyrrell, Jessica; Huikari, Ville; Christie, Jennifer T et al.

In: Human Molecular Genetics, Vol. 21, No. 24, 12.2012, p. 5344-58.

Research output: Contribution to journal › Journal article › Research › peer-review

Tyrrell, J, Huikari, V, Christie, JT, Cavadino, A, Bakker, R, Brion, M-JA, Geller, F, Paternoster, L, Myhre, R, Potter, C, Johnson, PCD, Ebrahim, S, Feenstra, B, Hartikainen, A-L, 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, M-R, Davey Smith, G, Freathy, RM & Early Growth Genetics (EGG) Consortium 2012, 'Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight', Human Molecular Genetics, vol. 21, no. 24, pp. 5344-58. https://doi.org/10.1093/hmg/dds372

@article{1ed89a650213420bb0573240de77c4bb,

title = "Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported 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 Anna-Liisa Hartikainen 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 Marjo-Riitta Jarvelin and {Davey Smith}, George and Freathy, {Rachel M} and S{\o}rensen, {Thorkild I.A.}",

year = "2012",

month = dec,

doi = "10.1093/hmg/dds372",

language = "English",

volume = "21",

pages = "5344--58",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "24",

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TY - JOUR

T1 - Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported 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 - Davey Smith, George

AU - Freathy, Rachel M

AU - Early Growth Genetics (EGG) Consortium

PY - 2012/12

Y1 - 2012/12

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.

U2 - 10.1093/hmg/dds372

DO - 10.1093/hmg/dds372

M3 - Journal article

SN - 0964-6906

VL - 21

SP - 5344

EP - 5358

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 24

ER -

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

Abstract

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