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Publication Detail
Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    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, 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 A, 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 AG, van Duijn CM, Wijga AH, Willemsen G, Zhang HT, Zhao JH, 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, GIANT Consortium , MAGIC , WTCCC , EGG Consortium
  • Publisher:
    NATURE PUBLISHING GROUP
  • Publication date:
    05/2010
  • Pagination:
    430, U73
  • Journal:
    NAT GENET
  • Volume:
    42
  • Issue:
    5
  • Print ISSN:
    1061-4036
  • Language:
    EN
  • Keywords:
    GENOME-WIDE ASSOCIATION, TYPE-2 DIABETES RISK, GESTATIONAL-AGE, HEAD CIRCUMFERENCE, ADENYLYL-CYCLASE, COHORT, GENE, METAANALYSIS, EXPRESSION, ISOFORMS
  • Addresses:
    Boomsma, DI
    Vrije Univ Amsterdam
    Dept Biol Psychol
    Amsterdam
    Netherlands

    Erasmus MC
    Generat Study R
    Rotterdam
    Netherlands

    Univ Oxford
    Wellcome Trust Ctr Human Genet
    Oxford
    England

    Univ Oulu
    Bioctr Oulu
    Oulu
    Finland

    Univ Munich
    Dr von Hauner Childrens Hosp
    Munich
    Germany

    Harvard Univ
    Sch Med
    Dept Pediat
    Boston
    MA
    02115
    USA

    Mahidol Univ
    Fac Trop Med
    Dept Trop Hyg
    Bangkok
    Thailand

    Univ London Imperial Coll Sci Technol & Med
    Hammersmith Hosp
    London
    England

    Univ Bristol
    Dept Social Med
    Bristol
    Avon
    England

    Massachusetts Inst Technol & Harvard
    Broad Inst
    Program Med & Populat Genet
    Cambridge
    MA
    02139
    USA

    Harvard Univ
    Sch Med
    Dept Genet
    Boston
    MA
    USA

    Childrens Hosp
    Div Endocrinol
    Boston
    MA
    02115
    USA

    Univ Groningen
    Univ Med Ctr
    Dept Pulmonol
    Perth
    WA
    Australia

    Univ London Imperial Coll Sci Technol & Med
    Natl Heart & Lung Inst
    Resp Epidemiol & Publ Hlth Grp
    London
    England

    Erasmus MC
    Dept Internal Med
    Rotterdam
    Netherlands

    Univ Helsinki
    Dept Gen Practice
    Helsinki
    Finland

    Folkhalsan Res Ctr
    Helsinki
    Finland

    Natl Inst Hlth & Welf
    Helsinki
    Finland

    Univ Penn
    Sch Med
    Dept Pediat
    Philadelphia
    PA
    19104
    USA

    Harvard Pilgrim Hlth Care Inst
    Boston
    MA
    USA

    Churchill Hosp
    Oxford NIHR Biomed Res Ctr
    Oxford
    OX3 7LJ
    England
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).
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