Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals

Tuomas O. Kilpeläinen; Marcel Den Hoed; Ken K. Ong; Anders Grøntved; Soren Brage; Karen Jameson; Cyrus Cooper; Kay Tee Khaw; Ulf Ekelund; Nicholas J. Wareham; Ruth J.F. Loos; Rachel M. Freathy; Dennis O. Mook-Kanamori; Ulla Sovio; Inga Prokopenko; Nicholas J. Timpson; Diane J. Berry; Nicole M. Warrington; Elisabeth Widen; Jouke Jan Hottenga; Marika Kaakinen; Leslie A. Lange; Jonathan P. Bradfield; Marjan Kerkhof; Julie A. Marsh; Reedik Mägi; Chih Mei Chen; Helen N. Lyon; Mirna Kirin; Linda S. Adair; Yurii S. Aulchenko; Amanda J. Bennett; Judith B. Borja; Nabila Bouatia-Naji; Pimphen Charoen; Lachlan J.M. Coin; Diana L. Cousminer; Eco J.C. De Geus; Panos Deloukas; Paul Elliott; David M. Evans; Philippe Froguel; Beate Glaser; Christopher J. Groves; Anna Liisa Hartikainen; Neelam Hassanali; Joel N. Hirschhorn; Albert Hofman; Jeff M.P. Holly; Elina Hyppönen; Stavroula Kanoni; Bridget A. Knight; Jaana Laitinen; Cecilia M. Lindgren; Wendy L. McArdle; Paul F. O'Reilly; Craig E. Pennell; Dirkje S. Postma; Anneli Pouta; Adaikalavan Ramasamy; Nigel W. Rayner; Susan M. Ring; Fernando Rivadeneira; Beverley M. Shields; David P. Strachan; Ida Surakka; Anja Taanila; Carla Tiesler; Andre G. Uitterlinden; Cornelia M. Van Duijn; Alet H. Wijga; Gonneke Willemsen; Haitao Zhang; Jianhua Zhao; James F. Wilson; Eric A.P. Steegers; Andrew T. Hattersley; Johan G. Eriksson; Leena Peltonen; Karen L. Mohlke; Struan F.A. Grant; Hakon Hakonarson; Gerard H. Koppelman; George V. Dedoussis; Joachim Heinrich; Matthew W. Gillman; Lyle J. Palmer; Timothy M. Frayling; Dorret I. Boomsma; George Davey Smith; Chris Power; Vincent W.V. Jaddoe; Marjo Riitta Jarvelin; Mark I. McCarthy

doi:10.3945/ajcn.110.000828

Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals

Tuomas O. Kilpeläinen, Marcel Den Hoed, Ken K. Ong, Anders Grøntved, Soren Brage, Karen Jameson, Cyrus Cooper, Kay Tee Khaw, Ulf Ekelund, Nicholas J. Wareham, Ruth J.F. Loos, Rachel M. Freathy, Dennis O. Mook-Kanamori, Ulla Sovio, Inga Prokopenko, Nicholas J. Timpson, Diane J. Berry, Nicole M. Warrington, Elisabeth Widen, Jouke Jan HottengaMarika Kaakinen, Leslie A. Lange, Jonathan P. Bradfield, Marjan Kerkhof, Julie A. Marsh, Reedik Mägi, Chih Mei Chen, Helen N. Lyon, Mirna Kirin, Linda S. Adair, Yurii S. Aulchenko, Amanda J. Bennett, Judith B. Borja, Nabila Bouatia-Naji, Pimphen Charoen, Lachlan J.M. Coin, Diana L. Cousminer, Eco J.C. De Geus, Panos Deloukas, Paul Elliott, David M. Evans, Philippe Froguel, Beate Glaser, Christopher J. Groves, Anna Liisa Hartikainen, Neelam Hassanali, Joel N. Hirschhorn, Albert Hofman, Jeff M.P. Holly, Elina Hyppönen, Stavroula Kanoni, Bridget A. Knight, Jaana Laitinen, Cecilia M. Lindgren, Wendy L. McArdle, Paul F. O'Reilly, Craig E. Pennell, Dirkje S. Postma, Anneli Pouta, Adaikalavan Ramasamy, Nigel W. Rayner, Susan M. Ring, Fernando Rivadeneira, Beverley M. Shields, David P. Strachan, Ida Surakka, Anja Taanila, Carla Tiesler, Andre G. Uitterlinden, Cornelia M. Van Duijn, Alet H. Wijga, Gonneke Willemsen, Haitao Zhang, Jianhua Zhao, James F. Wilson, Eric A.P. Steegers, Andrew T. Hattersley, Johan G. Eriksson, Leena Peltonen, Karen L. Mohlke, Struan F.A. Grant, Hakon Hakonarson, Gerard H. Koppelman, George V. Dedoussis, Joachim Heinrich, Matthew W. Gillman, Lyle J. Palmer, Timothy M. Frayling, Dorret I. Boomsma, George Davey Smith, Chris Power, Vincent W.V. Jaddoe, Marjo Riitta Jarvelin, Mark I. McCarthy

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Abstract

Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n_max = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n_max = 10,623); and 3) all published data (n_max = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

Original language	English
Pages (from-to)	851-860
Number of pages	10
Journal	American Journal of Clinical Nutrition
Volume	93
Issue number	4
DOIs	https://doi.org/10.3945/ajcn.110.000828
State	Published - 1 Apr 2011

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10.3945/ajcn.110.000828

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Kilpeläinen, T. O., Den Hoed, M., Ong, K. K., Grøntved, A., Brage, S., Jameson, K., Cooper, C., Khaw, K. T., Ekelund, U., Wareham, N. J., Loos, R. J. F., Freathy, R. M., Mook-Kanamori, D. O., Sovio, U., Prokopenko, I., Timpson, N. J., Berry, D. J., Warrington, N. M., Widen, E., ... McCarthy, M. I. (2011). Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals. American Journal of Clinical Nutrition, 93(4), 851-860. https://doi.org/10.3945/ajcn.110.000828

@article{7c4d7737fae3433b9411e20fb5b22ac7,

title = "Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals",

abstract = "Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.",

author = "Kilpel{\"a}inen, {Tuomas O.} and {Den Hoed}, Marcel and Ong, {Ken K.} and Anders Gr{\o}ntved and Soren Brage and Karen Jameson and Cyrus Cooper and Khaw, {Kay Tee} and Ulf Ekelund and Wareham, {Nicholas J.} and Loos, {Ruth J.F.} and Freathy, {Rachel M.} and Mook-Kanamori, {Dennis O.} and Ulla Sovio and Inga Prokopenko and Timpson, {Nicholas J.} and Berry, {Diane J.} and Warrington, {Nicole M.} and Elisabeth Widen and Hottenga, {Jouke Jan} and Marika Kaakinen and Lange, {Leslie A.} and Bradfield, {Jonathan P.} and Marjan Kerkhof and Marsh, {Julie A.} and Reedik M{\"a}gi and Chen, {Chih Mei} and Lyon, {Helen N.} and Mirna Kirin and Adair, {Linda S.} and Aulchenko, {Yurii S.} and Bennett, {Amanda J.} and Borja, {Judith B.} and Nabila Bouatia-Naji and Pimphen Charoen and Coin, {Lachlan J.M.} and Cousminer, {Diana L.} and {De Geus}, {Eco J.C.} and Panos Deloukas and Paul Elliott and Evans, {David M.} and Philippe Froguel and Beate Glaser and Groves, {Christopher J.} and Hartikainen, {Anna Liisa} and Neelam Hassanali and Hirschhorn, {Joel N.} and Albert Hofman and Holly, {Jeff M.P.} and Elina Hypp{\"o}nen and Stavroula Kanoni and Knight, {Bridget A.} and Jaana Laitinen and Lindgren, {Cecilia M.} and McArdle, {Wendy L.} and O'Reilly, {Paul F.} and Pennell, {Craig E.} and Postma, {Dirkje S.} and Anneli Pouta and Adaikalavan Ramasamy and Rayner, {Nigel W.} and Ring, {Susan M.} and Fernando Rivadeneira and Shields, {Beverley M.} and Strachan, {David P.} and Ida Surakka and Anja Taanila and Carla Tiesler and Uitterlinden, {Andre G.} and {Van Duijn}, {Cornelia M.} and Wijga, {Alet H.} and Gonneke Willemsen and Haitao Zhang and Jianhua Zhao and Wilson, {James F.} and Steegers, {Eric A.P.} and Hattersley, {Andrew T.} and Eriksson, {Johan G.} and Leena Peltonen and Mohlke, {Karen L.} and Grant, {Struan F.A.} and Hakon Hakonarson and Koppelman, {Gerard H.} and Dedoussis, {George V.} and Joachim Heinrich and Gillman, {Matthew W.} and Palmer, {Lyle J.} and Frayling, {Timothy M.} and Boomsma, {Dorret I.} and Smith, {George Davey} and Chris Power and Jaddoe, {Vincent W.V.} and Jarvelin, {Marjo Riitta} and McCarthy, {Mark I.}",

year = "2011",

month = apr,

day = "1",

doi = "10.3945/ajcn.110.000828",

language = "English",

volume = "93",

pages = "851--860",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Elsevier B.V.",

number = "4",

}

Kilpeläinen, TO, Den Hoed, M, Ong, KK, Grøntved, A, Brage, S, Jameson, K, Cooper, C, Khaw, KT, Ekelund, U, Wareham, NJ, Loos, RJF, Freathy, RM, Mook-Kanamori, DO, Sovio, U, Prokopenko, I, Timpson, NJ, Berry, DJ, Warrington, NM, Widen, E, Hottenga, JJ, Kaakinen, M, Lange, LA, Bradfield, JP, Kerkhof, M, Marsh, JA, Mägi, R, Chen, CM, Lyon, HN, Kirin, M, Adair, LS, Aulchenko, YS, Bennett, AJ, Borja, JB, Bouatia-Naji, N, Charoen, P, Coin, LJM, Cousminer, DL, De Geus, EJC, Deloukas, P, Elliott, P, Evans, DM, Froguel, P, Glaser, B, Groves, CJ, Hartikainen, AL, Hassanali, N, Hirschhorn, JN, Hofman, A, Holly, JMP, Hyppönen, E, Kanoni, S, Knight, BA, Laitinen, J, Lindgren, CM, McArdle, WL, O'Reilly, PF, Pennell, CE, Postma, DS, Pouta, A, Ramasamy, A, Rayner, NW, Ring, SM, Rivadeneira, F, Shields, BM, Strachan, DP, Surakka, I, Taanila, A, Tiesler, C, Uitterlinden, AG, Van Duijn, CM, Wijga, AH, Willemsen, G, Zhang, H, Zhao, J, Wilson, JF, Steegers, EAP, Hattersley, AT, Eriksson, JG, Peltonen, L, Mohlke, KL, Grant, SFA, Hakonarson, H, Koppelman, GH, Dedoussis, GV, Heinrich, J, Gillman, MW, Palmer, LJ, Frayling, TM, Boomsma, DI, Smith, GD, Power, C, Jaddoe, VWV, Jarvelin, MR & McCarthy, MI 2011, 'Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals', American Journal of Clinical Nutrition, vol. 93, no. 4, pp. 851-860. https://doi.org/10.3945/ajcn.110.000828

TY - JOUR

T1 - Obesity-susceptibility loci have a limited influence on birth weight

T2 - A meta-analysis of up to 28,219 individuals

AU - Kilpeläinen, Tuomas O.

AU - Den Hoed, Marcel

AU - Ong, Ken K.

AU - Grøntved, Anders

AU - Brage, Soren

AU - Jameson, Karen

AU - Cooper, Cyrus

AU - Khaw, Kay Tee

AU - Ekelund, Ulf

AU - Wareham, Nicholas J.

AU - Loos, Ruth J.F.

AU - Freathy, Rachel M.

AU - Mook-Kanamori, Dennis O.

AU - Sovio, Ulla

AU - Prokopenko, Inga

AU - Timpson, Nicholas J.

AU - Berry, Diane J.

AU - Warrington, Nicole M.

AU - Widen, Elisabeth

AU - Hottenga, Jouke Jan

AU - Kaakinen, Marika

AU - Lange, Leslie A.

AU - Bradfield, Jonathan P.

AU - Kerkhof, Marjan

AU - Marsh, Julie A.

AU - Mägi, Reedik

AU - Chen, Chih Mei

AU - Lyon, Helen N.

AU - Kirin, Mirna

AU - Adair, Linda S.

AU - Aulchenko, Yurii S.

AU - Bennett, Amanda J.

AU - Borja, Judith B.

AU - Bouatia-Naji, Nabila

AU - Charoen, Pimphen

AU - Coin, Lachlan J.M.

AU - Cousminer, Diana L.

AU - De Geus, Eco J.C.

AU - Deloukas, Panos

AU - Elliott, Paul

AU - Evans, David M.

AU - Froguel, Philippe

AU - Glaser, Beate

AU - Groves, Christopher J.

AU - Hartikainen, Anna Liisa

AU - Hassanali, Neelam

AU - Hirschhorn, Joel N.

AU - Hofman, Albert

AU - Holly, Jeff M.P.

AU - Hyppönen, Elina

AU - Kanoni, Stavroula

AU - Knight, Bridget A.

AU - Laitinen, Jaana

AU - Lindgren, Cecilia M.

AU - McArdle, Wendy L.

AU - O'Reilly, Paul F.

AU - Pennell, Craig E.

AU - Postma, Dirkje S.

AU - Pouta, Anneli

AU - Ramasamy, Adaikalavan

AU - Rayner, Nigel W.

AU - Ring, Susan M.

AU - Rivadeneira, Fernando

AU - Shields, Beverley M.

AU - Strachan, David P.

AU - Surakka, Ida

AU - Taanila, Anja

AU - Tiesler, Carla

AU - Uitterlinden, Andre G.

AU - Van Duijn, Cornelia M.

AU - Wijga, Alet H.

AU - Willemsen, Gonneke

AU - Zhang, Haitao

AU - Zhao, Jianhua

AU - Wilson, James F.

AU - Steegers, Eric A.P.

AU - Hattersley, Andrew T.

AU - Eriksson, Johan G.

AU - Peltonen, Leena

AU - Mohlke, Karen L.

AU - Grant, Struan F.A.

AU - Hakonarson, Hakon

AU - Koppelman, Gerard H.

AU - Dedoussis, George V.

AU - Heinrich, Joachim

AU - Gillman, Matthew W.

AU - Palmer, Lyle J.

AU - Frayling, Timothy M.

AU - Boomsma, Dorret I.

AU - Smith, George Davey

AU - Power, Chris

AU - Jaddoe, Vincent W.V.

AU - Jarvelin, Marjo Riitta

AU - McCarthy, Mark I.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

AB - Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

UR - http://www.scopus.com/inward/record.url?scp=79953230452&partnerID=8YFLogxK

U2 - 10.3945/ajcn.110.000828

DO - 10.3945/ajcn.110.000828

M3 - Article

C2 - 21248185

AN - SCOPUS:79953230452

SN - 0002-9165

VL - 93

SP - 851

EP - 860

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 4

ER -

Obesity-susceptibility loci have a limited influence on birth weight: A meta-analysis of up to 28,219 individuals

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