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

R M Freathy; DO Mook-Kanamori; U Sovio; I Prokopenko; Nicholas J Timpson; DJ Berry; NM Warrington; E Widen; JJ Hottenga; M Kaakinen; LA Lange; JP Bradfield; M Kerhof; JA Marsh; R Magi; CM Chen; HN Lyon; M Kirin; LS Adair; YS Aulchenko; AJ Bennett; JB Borja; N Bouatia-Naji; P Charoen; LJ Coin; DL Cousminer; EJ de Geus; P Deloukas; P Elliott; David Evans; P Froguel; CJ Groves; AL Hartikainen; N Hassanali; JN Hirschhorn; A Hofman; JMP Holly; E Hypponen; S Kanoni; BA Knight; J Laitnen; CM Lindgren; W L McArdle; PF O'Reily; CE Pennell; DS Postma; Susan M Ring; L  J Palmer; George Davey Smith; The Genetic Investigation of ANthropometric Traits (GIANT) Consortium; The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC); The Wellcome Trust Case Control Consortium (WTCCC); M U B St. Pourcain

doi:10.1038/ng.567

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

R M Freathy, DO Mook-Kanamori, U Sovio, I Prokopenko, Nicholas J Timpson, DJ Berry, NM Warrington, E Widen, JJ Hottenga, M Kaakinen, LA Lange, JP Bradfield, M Kerhof, JA Marsh, R Magi, CM Chen, HN Lyon, M Kirin, LS Adair, YS AulchenkoAJ Bennett, JB Borja, N Bouatia-Naji, P Charoen, LJ Coin, DL Cousminer, EJ de Geus, P Deloukas, P Elliott, David Evans, P Froguel, CJ Groves, AL Hartikainen, N Hassanali, JN Hirschhorn, A Hofman, JMP Holly, E Hypponen, S Kanoni, BA Knight, J Laitnen, CM Lindgren, W L McArdle, PF O'Reily, CE Pennell, DS Postma, Susan M Ring, L J Palmer, George Davey Smith, The Genetic Investigation of ANthropometric Traits (GIANT) Consortium, The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), The Wellcome Trust Case Control Consortium (WTCCC), M U B St. Pourcain

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

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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, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes 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.

Original language	English
Pages (from-to)	430-435
Number of pages	6
Journal	Nature Genetics
Volume	42
Issue number	5
Early online date	6 Apr 2010
DOIs	https://doi.org/10.1038/ng.567
Publication status	Published - May 2010

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Freathy, R. M., Mook-Kanamori, DO., Sovio, U., Prokopenko, I., Timpson, N. J., Berry, DJ., Warrington, NM., Widen, E., Hottenga, JJ., Kaakinen, M., Lange, LA., Bradfield, JP., Kerhof, M., Marsh, JA., Magi, R., Chen, CM., Lyon, HN., Kirin, M., Adair, LS., ... St. Pourcain, M. U. B. (2010). Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genetics, 42(5), 430-435. https://doi.org/10.1038/ng.567

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title = "Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight",

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, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes 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.",

author = "Freathy, {R M} and DO Mook-Kanamori and U Sovio and I Prokopenko and Timpson, {Nicholas J} and DJ Berry and NM Warrington and E Widen and JJ Hottenga and M Kaakinen and LA Lange and JP Bradfield and M Kerhof 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 LJ Coin and DL Cousminer and {de Geus}, EJ and P Deloukas and P Elliott and David Evans and P Froguel and CJ Groves and AL Hartikainen and N Hassanali and JN Hirschhorn and A Hofman and JMP Holly and E Hypponen and S Kanoni and BA Knight and J Laitnen and CM Lindgren and McArdle, {W L} and PF O'Reily and CE Pennell and DS Postma and Ring, {Susan M} and Palmer, {L J} and {Davey Smith}, George and {The Genetic Investigation of ANthropometric Traits (GIANT) Consortium} and {The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)} and {The Wellcome Trust Case Control Consortium (WTCCC)} and {St. Pourcain}, {M U B}",

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doi = "10.1038/ng.567",

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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, Kerhof, 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, LJ, Cousminer, DL, de Geus, EJ, Deloukas, P, Elliott, P, Evans, D, Froguel, P, Groves, CJ, Hartikainen, AL, Hassanali, N, Hirschhorn, JN, Hofman, A, Holly, JMP, Hypponen, E, Kanoni, S, Knight, BA, Laitnen, J, Lindgren, CM, McArdle, WL, O'Reily, PF, Pennell, CE, Postma, DS, Ring, SM, Palmer, LJ, Davey Smith, G, The Genetic Investigation of ANthropometric Traits (GIANT) Consortium, The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), The Wellcome Trust Case Control Consortium (WTCCC) & St. Pourcain, MUB 2010, 'Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight', Nature Genetics, vol. 42, no. 5, pp. 430-435. https://doi.org/10.1038/ng.567

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

AU - Freathy, R M

AU - Mook-Kanamori, DO

AU - Sovio, U

AU - Prokopenko, I

AU - Timpson, Nicholas J

AU - Berry, DJ

AU - Warrington, NM

AU - Widen, E

AU - Hottenga, JJ

AU - Kaakinen, M

AU - Lange, LA

AU - Bradfield, JP

AU - Kerhof, M

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, LJ

AU - Cousminer, DL

AU - de Geus, EJ

AU - Deloukas, P

AU - Elliott, P

AU - Evans, David

AU - Froguel, P

AU - Groves, CJ

AU - Hartikainen, AL

AU - Hassanali, N

AU - Hirschhorn, JN

AU - Hofman, A

AU - Holly, JMP

AU - Hypponen, E

AU - Kanoni, S

AU - Knight, BA

AU - Laitnen, J

AU - Lindgren, CM

AU - McArdle, W L

AU - O'Reily, PF

AU - Pennell, CE

AU - Postma, DS

AU - Ring, Susan M

AU - Palmer, L J

AU - Davey Smith, George

AU - The Genetic Investigation of ANthropometric Traits (GIANT) Consortium

AU - The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)

AU - The Wellcome Trust Case Control Consortium (WTCCC)

AU - St. Pourcain, M U B

PY - 2010/5

Y1 - 2010/5

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, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes 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.

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, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes 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.

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U2 - 10.1038/ng.567

DO - 10.1038/ng.567

M3 - Article (Academic Journal)

C2 - 20372150

SN - 1061-4036

VL - 42

SP - 430

EP - 435

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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

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