New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

M Horikoshi; H Yaghootkar; Dennis Mook; U Sovio; Rob Taal; BJ Hennig; JP Bradfield; B St Pourcain; DM Evans; P Charoen; M Kaakinen; DL Cousminer; T Lehtimaki; E Kreiner-Moller; NM Warrington; M Bustamante; B Feenstra; DJ Berry; E Thiering; T Pfab; SJ Barton; BM Shields; Marjon Kerkhof; Elisa Leeuwen; AJ Fulford; Z Kutalik; M den Hoed; A Mahajan; V Lindi; LK Goh; JJ (Jouke Jan) Hottenga; Fenny Wu; OT Raitakari; MN Harder; A Meirhaeghe; I Ntalla; RM Salem; KA Jameson; KX Zhou; DM Monies; V Lagou; M Kirin; J Heikkinen; LS Adair; FS Alkuraya; A Al-Odaib; P Amouyel; EA Andersson; AJ Bennett; AIF Blakemore; JL Buxton; J Dallongeville; Suman Das; EJC de Geus; X Estivill; C Flexeder; P Froguel; F Geller; KM Godfrey; F Gottrand; CJ Groves; T Hansen; JN Hirschhorn; Bert Hofman; MV Hollegaard; DM Hougaard; E Hypponen; HM Inskip; Aaron Isaacs; T Jorgensen; C Kanaka-Gantenbein; JP Kemp; W Kiess; TO Kilpelainen; N Klopp; BA Knight; CW Kuzawa; G McMahon; JP Newnham; H Niinikoski; Ben Oostra; L Pedersen; DS Postma; SM Ring; Fernando Rivadeneira; NR Robertson; S Sebert; O Simell; T Slowinski; CMT Tiesler; A Tonjes; A Vaag; JS Viikari; JM Vink; NH Vissing; NJ Wareham; G Willemsen; DR Witte; HT Zhang; JH Zhao; JF Wilson; M Stumvoll; AM Prentice; BF Meyer; ER Pearson; CAG Boreham; C Cooper; MW Gillman; GV Dedoussis; LA Moreno; O Pedersen; M Saarinen; KL Mohlke; DI Boomsma; SM Saw; TA Lakka; A Korner; RJF Loos; KK Ong; P Vollenweider; Cornelia Duijn; GH Koppelman; AT Hattersley; JW Holloway; B Hocher; J (Joachim) Heinrich; C Power; M Melbye; Monica Guxens Junyent; CE Pennell; K Bonnelykke; H Bisgaard; JG Eriksson; E Widen; H Hakonarson; André Uitterlinden; A Pouta; DA Lawlor; GD Smith; TM Frayling; MI McCarthy; SFA Grant; Vincent Jaddoe; MR Jarvelin; NJ Timpson; I Prokopenko; RM Freathy

doi:10.1038/ng.2477

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

M Horikoshi, H Yaghootkar, Dennis Mook, U Sovio, Rob Taal, BJ Hennig, JP Bradfield, B St Pourcain, DM Evans, P Charoen, M Kaakinen, DL Cousminer, T Lehtimaki, E Kreiner-Moller, NM Warrington, M Bustamante, B Feenstra, DJ Berry, E Thiering, T PfabSJ Barton, BM Shields, Marjon Kerkhof, Elisa Leeuwen, AJ Fulford, Z Kutalik, M den Hoed, A Mahajan, V Lindi, LK Goh, JJ (Jouke Jan) Hottenga, Fenny Wu, OT Raitakari, MN Harder, A Meirhaeghe, I Ntalla, RM Salem, KA Jameson, KX Zhou, DM Monies, V Lagou, M Kirin, J Heikkinen, LS Adair, FS Alkuraya, A Al-Odaib, P Amouyel, EA Andersson, AJ Bennett, AIF Blakemore, JL Buxton, J Dallongeville, Suman Das, EJC de Geus, X Estivill, C Flexeder, P Froguel, F Geller, KM Godfrey, F Gottrand, CJ Groves, T Hansen, JN Hirschhorn, Bert Hofman, MV Hollegaard, DM Hougaard, E Hypponen, HM Inskip, Aaron Isaacs, T Jorgensen, C Kanaka-Gantenbein, JP Kemp, W Kiess, TO Kilpelainen, N Klopp, BA Knight, CW Kuzawa, G McMahon, JP Newnham, H Niinikoski, Ben Oostra, L Pedersen, DS Postma, SM Ring, Fernando Rivadeneira, NR Robertson, S Sebert, O Simell, T Slowinski, CMT Tiesler, A Tonjes, A Vaag, JS Viikari, JM Vink, NH Vissing, NJ Wareham, G Willemsen, DR Witte, HT Zhang, JH Zhao, JF Wilson, M Stumvoll, AM Prentice, BF Meyer, ER Pearson, CAG Boreham, C Cooper, MW Gillman, GV Dedoussis, LA Moreno, O Pedersen, M Saarinen, KL Mohlke, DI Boomsma, SM Saw, TA Lakka, A Korner, RJF Loos, KK Ong, P Vollenweider, Cornelia Duijn, GH Koppelman, AT Hattersley, JW Holloway, B Hocher, J (Joachim) Heinrich, C Power, M Melbye, Monica Guxens Junyent, CE Pennell, K Bonnelykke, H Bisgaard, JG Eriksson, E Widen, H Hakonarson, André Uitterlinden, A Pouta, DA Lawlor, GD Smith, TM Frayling, MI McCarthy, SFA Grant, Vincent Jaddoe, MR Jarvelin, NJ Timpson, I Prokopenko, RM Freathy

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Original language	Undefined/Unknown
Pages (from-to)	76-U115
Journal	Nature Genetics
Volume	45
Issue number	1
DOIs	https://doi.org/10.1038/ng.2477
Publication status	Published - 2013

Research programs

EMC MM-04-54-08-A
EMC NIHES-01-64-02

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2477

http://hdl.handle.net/1765/54116

Cite this

Horikoshi, M., Yaghootkar, H., Mook, D., Sovio, U., Taal, R., Hennig, BJ., Bradfield, JP., St Pourcain, B., Evans, DM., Charoen, P., Kaakinen, M., Cousminer, DL., Lehtimaki, T., Kreiner-Moller, E., Warrington, NM., Bustamante, M., Feenstra, B., Berry, DJ., Thiering, E., ... Freathy, RM. (2013). New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nature Genetics, 45(1), 76-U115. https://doi.org/10.1038/ng.2477

@article{258ea56b4c5240b1ab345fdaaf905066,

title = "New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism",

abstract = "Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.",

author = "M Horikoshi and H Yaghootkar and Dennis Mook and U Sovio and Rob Taal and BJ Hennig and JP Bradfield and {St Pourcain}, B and DM Evans and P Charoen and M Kaakinen and DL Cousminer and T Lehtimaki and E Kreiner-Moller and NM Warrington and M Bustamante and B Feenstra and DJ Berry and E Thiering and T Pfab and SJ Barton and BM Shields and Marjon Kerkhof and Elisa Leeuwen and AJ Fulford and Z Kutalik and {den Hoed}, M and A Mahajan and V Lindi and LK Goh and Hottenga, {JJ (Jouke Jan)} and Fenny Wu and OT Raitakari and MN Harder and A Meirhaeghe and I Ntalla and RM Salem and KA Jameson and KX Zhou and DM Monies and V Lagou and M Kirin and J Heikkinen and LS Adair and FS Alkuraya and A Al-Odaib and P Amouyel and EA Andersson and AJ Bennett and AIF Blakemore and JL Buxton and J Dallongeville and Suman Das and {de Geus}, EJC and X Estivill and C Flexeder and P Froguel and F Geller and KM Godfrey and F Gottrand and CJ Groves and T Hansen and JN Hirschhorn and Bert Hofman and MV Hollegaard and DM Hougaard and E Hypponen and HM Inskip and Aaron Isaacs and T Jorgensen and C Kanaka-Gantenbein and JP Kemp and W Kiess and TO Kilpelainen and N Klopp and BA Knight and CW Kuzawa and G McMahon and JP Newnham and H Niinikoski and Ben Oostra and L Pedersen and DS Postma and SM Ring and Fernando Rivadeneira and NR Robertson and S Sebert and O Simell and T Slowinski and CMT Tiesler and A Tonjes and A Vaag and JS Viikari and JM Vink and NH Vissing and NJ Wareham and G Willemsen and DR Witte and HT Zhang and JH Zhao and JF Wilson and M Stumvoll and AM Prentice and BF Meyer and ER Pearson and CAG Boreham and C Cooper and MW Gillman and GV Dedoussis and LA Moreno and O Pedersen and M Saarinen and KL Mohlke and DI Boomsma and SM Saw and TA Lakka and A Korner and RJF Loos and KK Ong and P Vollenweider and Cornelia Duijn and GH Koppelman and AT Hattersley and JW Holloway and B Hocher and Heinrich, {J (Joachim)} and C Power and M Melbye and {Guxens Junyent}, Monica and CE Pennell and K Bonnelykke and H Bisgaard and JG Eriksson and E Widen and H Hakonarson and Andr{\'e} Uitterlinden and A Pouta and DA Lawlor and GD Smith and TM Frayling and MI McCarthy and SFA Grant and Vincent Jaddoe and MR Jarvelin and NJ Timpson and I Prokopenko and RM Freathy",

year = "2013",

doi = "10.1038/ng.2477",

language = "Undefined/Unknown",

volume = "45",

pages = "76--U115",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

}

Horikoshi, M, Yaghootkar, H, Mook, D, Sovio, U, Taal, R, Hennig, BJ, Bradfield, JP, St Pourcain, B, Evans, DM, Charoen, P, Kaakinen, M, Cousminer, DL, Lehtimaki, T, Kreiner-Moller, E, Warrington, NM, Bustamante, M, Feenstra, B, Berry, DJ, Thiering, E, Pfab, T, Barton, SJ, Shields, BM, Kerkhof, M, Leeuwen, E, Fulford, AJ, Kutalik, Z, den Hoed, M, Mahajan, A, Lindi, V, Goh, LK, Hottenga, JJ, Wu, F, Raitakari, OT, Harder, MN, Meirhaeghe, A, Ntalla, I, Salem, RM, Jameson, KA, Zhou, KX, Monies, DM, Lagou, V, Kirin, M, Heikkinen, J, Adair, LS, Alkuraya, FS, Al-Odaib, A, Amouyel, P, Andersson, EA, Bennett, AJ, Blakemore, AIF, Buxton, JL, Dallongeville, J, Das, S, de Geus, EJC, Estivill, X, Flexeder, C, Froguel, P, Geller, F, Godfrey, KM, Gottrand, F, Groves, CJ, Hansen, T, Hirschhorn, JN, Hofman, B, Hollegaard, MV, Hougaard, DM, Hypponen, E, Inskip, HM, Isaacs, A, Jorgensen, T, Kanaka-Gantenbein, C, Kemp, JP, Kiess, W, Kilpelainen, TO, Klopp, N, Knight, BA, Kuzawa, CW, McMahon, G, Newnham, JP, Niinikoski, H, Oostra, B, Pedersen, L, Postma, DS, Ring, SM, Rivadeneira, F, Robertson, NR, Sebert, S, Simell, O, Slowinski, T, Tiesler, CMT, Tonjes, A, Vaag, A, Viikari, JS, Vink, JM, Vissing, NH, Wareham, NJ, Willemsen, G, Witte, DR, Zhang, HT, Zhao, JH, Wilson, JF, Stumvoll, M, Prentice, AM, Meyer, BF, Pearson, ER, Boreham, CAG, Cooper, C, Gillman, MW, Dedoussis, GV, Moreno, LA, Pedersen, O, Saarinen, M, Mohlke, KL, Boomsma, DI, Saw, SM, Lakka, TA, Korner, A, Loos, RJF, Ong, KK, Vollenweider, P, Duijn, C, Koppelman, GH, Hattersley, AT, Holloway, JW, Hocher, B, Heinrich, J, Power, C, Melbye, M, Guxens Junyent, M, Pennell, CE, Bonnelykke, K, Bisgaard, H, Eriksson, JG, Widen, E, Hakonarson, H, Uitterlinden, A, Pouta, A, Lawlor, DA, Smith, GD, Frayling, TM, McCarthy, MI, Grant, SFA, Jaddoe, V, Jarvelin, MR, Timpson, NJ, Prokopenko, I & Freathy, RM 2013, 'New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism', Nature Genetics, vol. 45, no. 1, pp. 76-U115. https://doi.org/10.1038/ng.2477

TY - JOUR

T1 - New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

AU - Horikoshi, M

AU - Yaghootkar, H

AU - Mook, Dennis

AU - Sovio, U

AU - Taal, Rob

AU - Hennig, BJ

AU - Bradfield, JP

AU - St Pourcain, B

AU - Evans, DM

AU - Charoen, P

AU - Kaakinen, M

AU - Cousminer, DL

AU - Lehtimaki, T

AU - Kreiner-Moller, E

AU - Warrington, NM

AU - Bustamante, M

AU - Feenstra, B

AU - Berry, DJ

AU - Thiering, E

AU - Pfab, T

AU - Barton, SJ

AU - Shields, BM

AU - Kerkhof, Marjon

AU - Leeuwen, Elisa

AU - Fulford, AJ

AU - Kutalik, Z

AU - den Hoed, M

AU - Mahajan, A

AU - Lindi, V

AU - Goh, LK

AU - Hottenga, JJ (Jouke Jan)

AU - Wu, Fenny

AU - Raitakari, OT

AU - Harder, MN

AU - Meirhaeghe, A

AU - Ntalla, I

AU - Salem, RM

AU - Jameson, KA

AU - Zhou, KX

AU - Monies, DM

AU - Lagou, V

AU - Kirin, M

AU - Heikkinen, J

AU - Adair, LS

AU - Alkuraya, FS

AU - Al-Odaib, A

AU - Amouyel, P

AU - Andersson, EA

AU - Bennett, AJ

AU - Blakemore, AIF

AU - Buxton, JL

AU - Dallongeville, J

AU - Das, Suman

AU - de Geus, EJC

AU - Estivill, X

AU - Flexeder, C

AU - Froguel, P

AU - Geller, F

AU - Godfrey, KM

AU - Gottrand, F

AU - Groves, CJ

AU - Hansen, T

AU - Hirschhorn, JN

AU - Hofman, Bert

AU - Hollegaard, MV

AU - Hougaard, DM

AU - Hypponen, E

AU - Inskip, HM

AU - Isaacs, Aaron

AU - Jorgensen, T

AU - Kanaka-Gantenbein, C

AU - Kemp, JP

AU - Kiess, W

AU - Kilpelainen, TO

AU - Klopp, N

AU - Knight, BA

AU - Kuzawa, CW

AU - McMahon, G

AU - Newnham, JP

AU - Niinikoski, H

AU - Oostra, Ben

AU - Pedersen, L

AU - Postma, DS

AU - Ring, SM

AU - Rivadeneira, Fernando

AU - Robertson, NR

AU - Sebert, S

AU - Simell, O

AU - Slowinski, T

AU - Tiesler, CMT

AU - Tonjes, A

AU - Vaag, A

AU - Viikari, JS

AU - Vink, JM

AU - Vissing, NH

AU - Wareham, NJ

AU - Willemsen, G

AU - Witte, DR

AU - Zhang, HT

AU - Zhao, JH

AU - Wilson, JF

AU - Stumvoll, M

AU - Prentice, AM

AU - Meyer, BF

AU - Pearson, ER

AU - Boreham, CAG

AU - Cooper, C

AU - Gillman, MW

AU - Dedoussis, GV

AU - Moreno, LA

AU - Pedersen, O

AU - Saarinen, M

AU - Mohlke, KL

AU - Boomsma, DI

AU - Saw, SM

AU - Lakka, TA

AU - Korner, A

AU - Loos, RJF

AU - Ong, KK

AU - Vollenweider, P

AU - Duijn, Cornelia

AU - Koppelman, GH

AU - Hattersley, AT

AU - Holloway, JW

AU - Hocher, B

AU - Heinrich, J (Joachim)

AU - Power, C

AU - Melbye, M

AU - Guxens Junyent, Monica

AU - Pennell, CE

AU - Bonnelykke, K

AU - Bisgaard, H

AU - Eriksson, JG

AU - Widen, E

AU - Hakonarson, H

AU - Uitterlinden, André

AU - Pouta, A

AU - Lawlor, DA

AU - Smith, GD

AU - Frayling, TM

AU - McCarthy, MI

AU - Grant, SFA

AU - Jaddoe, Vincent

AU - Jarvelin, MR

AU - Timpson, NJ

AU - Prokopenko, I

AU - Freathy, RM

PY - 2013

Y1 - 2013

N2 - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

AB - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

U2 - 10.1038/ng.2477

DO - 10.1038/ng.2477

M3 - Article

C2 - 23202124

SN - 1061-4036

VL - 45

SP - 76-U115

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -