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 journalArticle (Academic Journal)peer-review

197 Citations (Scopus)


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 languageEnglish
Pages (from-to)430-435
Number of pages6
JournalNature Genetics
Issue number5
Early online date6 Apr 2010
Publication statusPublished - May 2010


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