Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

RM Freathy; Dennis Mook; U Sovio; I Prokopenko; NJ Timpson; DJ Berry; NM Warrington; E Widen; JJ (Jouke Jan) Hottenga; M Kaakinen; LA Lange; JP Bradfield; Marjon Kerkhof; JA Marsh; R Magi; CM Chen; HN Lyon; M Kirin; LS Adair; YS Aulchenko; AJ Bennett; JB Borja; N Bouatia-Naji; P Charoen; LJM Coin; DL Cousminer; EJC de Geus; P Deloukas; P Elliott; DM Evans; P Froguel; B Glaser; CJ Groves; AL Hartikainen; N Hassanali; JN Hirschhorn; Bert Hofman; JMP Holly; E Hypponen; S Kanoni; BA Knight; J Laitinen; CM Lindgren; WL McArdle; PF O'Reilly; CE Pennell; DS Postma; A Pouta; A Ramasamy; NW Rayner; SM Ring; Fernando Rivadeneira; BM Shields; DP Strachan; I Surakka; A Taanila; C Tiesler; André Uitterlinden; Cornelia Duijn; AH Wijga; G Willemsen; HT Zhang; JH Zhao; JF Wilson; Eric Steegers; AT Hattersley; JG Eriksson; L Peltonen; KL Mohlke; SFA Grant; H Hakonarson; GH Koppelman; GV Dedoussis; J (Joachim) Heinrich; MW Gillman; LJ Palmer; TM Frayling; DI Boomsma; GD Smith; C Power; Vincent Jaddoe; MR Jarvelin; MI McCarthy

doi:10.1038/ng.567

Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

RM Freathy
, Dennis Mook
, U Sovio
, I Prokopenko
, NJ Timpson
, DJ Berry
, NM Warrington
, E Widen
, JJ (Jouke Jan) Hottenga
, M Kaakinen
, LA Lange
, JP Bradfield
, Marjon Kerkhof
, JA Marsh
, R Magi
, CM Chen
, HN Lyon
, M Kirin
, LS Adair
, YS Aulchenko

AJ Bennett, JB Borja, N Bouatia-Naji, P Charoen, LJM Coin, DL Cousminer, EJC de Geus, P Deloukas, P Elliott, DM Evans, P Froguel, B Glaser, CJ Groves, AL Hartikainen, N Hassanali, JN Hirschhorn, Bert Hofman, JMP Holly, E Hypponen, S Kanoni, BA Knight, J Laitinen, CM Lindgren, WL McArdle, PF O'Reilly, CE Pennell, DS Postma, A Pouta, A Ramasamy, NW Rayner, SM Ring, Fernando Rivadeneira, BM Shields, DP Strachan, I Surakka, A Taanila, C Tiesler, André Uitterlinden, Cornelia Duijn, AH Wijga, G Willemsen, HT Zhang, JH Zhao, JF Wilson, Eric Steegers, AT Hattersley, JG Eriksson, L Peltonen, KL Mohlke, SFA Grant, H Hakonarson, GH Koppelman, GV Dedoussis, J (Joachim) Heinrich, MW Gillman, LJ Palmer, TM Frayling, DI Boomsma, GD Smith, C Power, Vincent Jaddoe, MR Jarvelin, MI McCarthy

External organisation

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

211 Citations (Scopus)

Abstract

To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P-trend = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy(4).

Original language	Undefined/Unknown
Pages (from-to)	430-U73
Journal	Nature Genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.567
Publication status	Published - 2010

UN SDGs

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

SDG 3 Good Health and Well-being

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RSM LIS
EMC MGC-02-52-01-A
EMC MM-01-39-02
EMC MM-04-54-08-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

Access to Document

10.1038/ng.567

http://hdl.handle.net/1765/28299

Cite this

Freathy, RM., Mook, D., Sovio, U., Prokopenko, I., Timpson, NJ., Berry, DJ., Warrington, NM., Widen, E., Hottenga, JJ., Kaakinen, M., Lange, LA., Bradfield, JP., Kerkhof, M., Marsh, JA., Magi, R., Chen, CM., Lyon, HN., Kirin, M., Adair, LS., ... McCarthy, MI. (2010). Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genetics, 42(5), 430-U73. https://doi.org/10.1038/ng.567

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abstract = "To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9\% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95\% CI 89-137 g) lighter at birth than the 24\% with zero or one alleles (P-trend = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy(4).",

author = "RM Freathy and Dennis Mook and U Sovio and I Prokopenko and NJ Timpson and DJ Berry and NM Warrington and E Widen and Hottenga, \{JJ (Jouke Jan)\} and M Kaakinen and LA Lange and JP Bradfield and Marjon Kerkhof and JA Marsh and R Magi and CM Chen and HN Lyon and M Kirin and LS Adair and YS Aulchenko and AJ Bennett and JB Borja and N Bouatia-Naji and P Charoen and LJM Coin and DL Cousminer and \{de Geus\}, EJC and P Deloukas and P Elliott and DM Evans and P Froguel and B Glaser and CJ Groves and AL Hartikainen and N Hassanali and JN Hirschhorn and Bert Hofman and JMP Holly and E Hypponen and S Kanoni and BA Knight and J Laitinen and CM Lindgren and WL McArdle and PF O'Reilly and CE Pennell and DS Postma and A Pouta and A Ramasamy and NW Rayner and SM Ring and Fernando Rivadeneira and BM Shields and DP Strachan and I Surakka and A Taanila and C Tiesler and Andr{\'e} Uitterlinden and Cornelia Duijn and AH Wijga and G Willemsen and HT Zhang and JH Zhao and JF Wilson and Eric Steegers and AT Hattersley and JG Eriksson and L Peltonen and KL Mohlke and SFA Grant and H Hakonarson and GH Koppelman and GV Dedoussis and Heinrich, \{J (Joachim)\} and MW Gillman and LJ Palmer and TM Frayling and DI Boomsma and GD Smith and C Power and Vincent Jaddoe and MR Jarvelin and MI McCarthy",

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Freathy, RM, Mook, D, Sovio, U, Prokopenko, I, Timpson, NJ, Berry, DJ, Warrington, NM, Widen, E, Hottenga, JJ, Kaakinen, M, Lange, LA, Bradfield, JP, Kerkhof, M, Marsh, JA, Magi, 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, B, Holly, JMP, Hypponen, 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, A, Duijn, C, Wijga, AH, Willemsen, G, Zhang, HT, Zhao, JH, Wilson, JF, Steegers, E, 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, V, Jarvelin, MR & McCarthy, MI 2010, 'Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight', Nature Genetics, vol. 42, no. 5, pp. 430-U73. https://doi.org/10.1038/ng.567

TY - JOUR

T1 - Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

AU - Freathy, RM

AU - Mook, Dennis

AU - Sovio, U

AU - Prokopenko, I

AU - Timpson, NJ

AU - Berry, DJ

AU - Warrington, NM

AU - Widen, E

AU - Hottenga, JJ (Jouke Jan)

AU - Kaakinen, M

AU - Lange, LA

AU - Bradfield, JP

AU - Kerkhof, Marjon

AU - Marsh, JA

AU - Magi, R

AU - Chen, CM

AU - Lyon, HN

AU - Kirin, M

AU - Adair, LS

AU - Aulchenko, YS

AU - Bennett, AJ

AU - Borja, JB

AU - Bouatia-Naji, N

AU - Charoen, P

AU - Coin, LJM

AU - Cousminer, DL

AU - de Geus, EJC

AU - Deloukas, P

AU - Elliott, P

AU - Evans, DM

AU - Froguel, P

AU - Glaser, B

AU - Groves, CJ

AU - Hartikainen, AL

AU - Hassanali, N

AU - Hirschhorn, JN

AU - Hofman, Bert

AU - Holly, JMP

AU - Hypponen, E

AU - Kanoni, S

AU - Knight, BA

AU - Laitinen, J

AU - Lindgren, CM

AU - McArdle, WL

AU - O'Reilly, PF

AU - Pennell, CE

AU - Postma, DS

AU - Pouta, A

AU - Ramasamy, A

AU - Rayner, NW

AU - Ring, SM

AU - Rivadeneira, Fernando

AU - Shields, BM

AU - Strachan, DP

AU - Surakka, I

AU - Taanila, A

AU - Tiesler, C

AU - Uitterlinden, André

AU - Duijn, Cornelia

AU - Wijga, AH

AU - Willemsen, G

AU - Zhang, HT

AU - Zhao, JH

AU - Wilson, JF

AU - Steegers, Eric

AU - Hattersley, AT

AU - Eriksson, JG

AU - Peltonen, L

AU - Mohlke, KL

AU - Grant, SFA

AU - Hakonarson, H

AU - Koppelman, GH

AU - Dedoussis, GV

AU - Heinrich, J (Joachim)

AU - Gillman, MW

AU - Palmer, LJ

AU - Frayling, TM

AU - Boomsma, DI

AU - Smith, GD

AU - Power, C

AU - Jaddoe, Vincent

AU - Jarvelin, MR

AU - McCarthy, MI

PY - 2010

Y1 - 2010

N2 - To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P-trend = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy(4).

AB - To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P-trend = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy(4).

U2 - 10.1038/ng.567

DO - 10.1038/ng.567

M3 - Article

C2 - 20372150

SN - 1061-4036

VL - 42

SP - 430-U73

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -