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

被引：188

作者：

Freathy, Rachel M.

Mook-Kanamori, Dennis O. ^{[2
,3
,4
]}

Sovio, Ulla ^{[5
]}

Prokopenko, Inga ^{[6
,7
]}

Timpson, Nicholas J. ^{[8
]}

Berry, Diane J. ^{[9
]}

Warrington, Nicole M. ^{[10
]}

Widen, Elisabeth ^{[11
]}

Hottenga, Jouke Jan ^{[1
]}

Kaakinen, Marika ^{[12
,13
]}

Lange, Leslie A. ^{[14
]}

Bradfield, Jonathan P. ^{[15
]}

Kerkhof, Marjan ^{[16
]}

Marsh, Julie A. ^{[10
]}

Maegi, Reedik ^{[6
,7
]}

Chen, Chih-Mei ^{[17
,18
]}

Lyon, Helen N. ^{[19
,20
]}

Kirin, Mirna ^{[21
]}

Adair, Linda S. ^{[22
]}

Aulchenko, Yurii S. ^{[3
]}

Bennett, Amanda J. ^{[6
]}

Borja, Judith B. ^{[23
]}

Bouatia-Naji, Nabila ^{[24
]}

Charoen, Pimphen ^{[5
,25
]}

Coin, Lachlan J. M. ^{[5
]}

Cousminer, Diana L. ^{[11
]}

de Geus, Eco J. C. ^{[1
]}

Deloukas, Panos ^{[26
]}

Elliott, Paul ^{[5
]}

Evans, David M. ^{[8
]}

Froguel, Philippe ^{[24
,27
]}

Glaser, Beate ^{[8
,28
]}

Groves, Christopher J. ^{[6
]}

Hartikainen, Anna-Liisa ^{[29
]}

Hassanali, Neelam ^{[6
]}

Hirschhorn, Joel N. ^{[19
,30
,31
,32
]}

Hofman, Albert ^{[3
]}

Holly, Jeff M. P. ^{[33
]}

Hyppoenen, Elina ^{[9
]}

Kanoni, Stavroula ^{[34
]}

Knight, Bridget A. ^{[35
]}

Laitinen, Jaana ^{[36
]}

Lindgren, Cecilia M. ^{[6
,7
]}

McArdle, Wendy L. ^{[37
]}

O'Reilly, Paul F. ^{[5
]}

Pennell, Craig E.

Postma, Dirkje S. ^{[38
,39
]}

Pouta, Anneli ^{[40
]}

Ramasamy, Adaikalavan ^{[5
,41
]}

Rayner, Nigel W. ^{[6
,7
]}

机构：

[1] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[2] Erasmus MC, Dept Pediat, Rotterdam, Netherlands

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Erasmus MC, Generat Study R, Rotterdam, Netherlands

[5] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[6] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England

[7] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[8] Univ Bristol, Dept Social Med, Ctr Causal Anal Translat Epidemiol, MRC, Bristol, Avon, England

[9] UCL, Inst Child Hlth, Ctr Epidemiol Child Hlth, Ctr Paediat Epidemiol & Biostat,MRC, London, England

[10] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Perth, WA 6009, Australia

[11] Univ Helsinki, FIMM, Helsinki, Finland

[12] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[13] Univ Oulu, Bioctr Oulu, Oulu, Finland

[14] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[15] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA USA

[16] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[17] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany

[18] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany

[19] Childrens Hosp, Program Genom, Div Genet, Boston, MA 02115 USA

[20] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[21] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[22] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA

[23] Univ San Carlos, Off Populat Studies Fdn, Cebu, Philippines

[24] Inst Pasteur, Inst Biol, CNRS, UMR 8199, F-59019 Lille, France

[25] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok, Thailand

[26] Wellcome Trust Sanger Inst, Cambridge, England

[27] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England

[28] Univ Bristol, Dept Social Med, Bristol, Avon, England

[29] Univ Oulu, Inst Clin Med, Oulu, Finland

[30] Massachusetts Inst Technol & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA

[31] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[32] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[33] Univ Bristol, Southmead Hosp, Dept Clin Sci N Bristol, Paul OGorman Lifeline Ctr, Bristol, Avon, England

[34] Harokopio Univ, Dept Dietet Nutr, Athens, Greece

[35] Univ Exeter, Peninsula Coll Med & Dent, Peninsula Natl Inst Hlth Res NIHR, Clin Res Facil, Exeter, Devon, England

[36] Oulu Reg Inst Occupat Hlth, Oulu, Finland

[37] Univ Bristol, Dept Social Med, Bristol, Avon, England

[38] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia

[39] Univ Groningen, Univ Med Ctr, Dept Pulmonol, Perth, WA, Australia

[40] Natl Inst Hlth & Welf, Oulu, Finland

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

[42] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[43] Univ London, Div Community Hlth Sci, London, England

[44] Natl Inst Publ Hlth & Environm RIVM, Ctr Prevent & Hlth Serv Res, Bilthoven, Netherlands

[45] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA USA

[46] Erasmus MC, Dept Obstet & Gynecol, Rotterdam, Netherlands

[47] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland

[48] Univ Helsinki, Dept Gen Practice, Helsinki, Finland

[49] Folkhalsan Res Ctr, Helsinki, Finland

[50] Natl Inst Hlth & Welf, Helsinki, Finland

来源：

NATURE GENETICS | 2010年 / 42卷 / 05期

基金：

美国国家卫生研究院; 加拿大健康研究院; 英国惠康基金; 英国医学研究理事会; 芬兰科学院;

关键词：

GENOME-WIDE ASSOCIATION; HEAD CIRCUMFERENCE; GESTATIONAL-AGE; GENE; METAANALYSIS; LENGTH; COHORT; LOCI;

D O I：

10.1038/ng.567

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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).

引用

页码：430 / U73

页数：8

共 38 条

[1]

ACKER DB, 1985, OBSTET GYNECOL, V66, P762

[2]

[Anonymous], METAN STATA MODULE F

[3] TYPE 2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS, HYPERTENSION AND HYPERLIPEMIA (SYNDROME-X) - RELATION TO REDUCED FETAL GROWTH [J].

BARKER, DJP ;

HALES, CN ;

FALL, CHD ;

OSMOND, C ;

PHIPPS, K ;

CLARK, PMS .

DIABETOLOGIA, 1993, 36 (01) :62-67

[4] A PRACTICAL CLASSIFICATION OF NEWBORN INFANTS BY WEIGHT AND GESTATIONAL AGE [J].

BATTAGLI.FC ;

LUBCHENC.LO .

JOURNAL OF PEDIATRICS, 1967, 71 (02) :159-+

[5] Maternal smoking and its association with birth weight [J].

Bernstein, IM ;

Mongeon, JA ;

Badger, GJ ;

Solomon, L ;

Heil, SH ;

Higgins, ST .

OBSTETRICS AND GYNECOLOGY, 2005, 106 (05) :986-991

[6] cAMP-coupled riboflavin trafficking in placental trophoblasts: A dynamic and ordered process [J].

D'Souza, Vanessa M. ;

Foraker, Amy B. ;

Free, R. Benjamin ;

Ray, Abhijit ;

Shapiro, Paul S. ;

Swaan, Peter W. .

BIOCHEMISTRY, 2006, 45 (19) :6095-6104

[7] Practical aspects of imputation-driven meta-analysis of genome-wide association studies [J].

de Bakker, Paul I. W. ;

Ferreira, Manuel A. R. ;

Jia, Xiaoming ;

Neale, Benjamin M. ;

Raychaudhuri, Soumya ;

Voight, Benjamin F. .

HUMAN MOLECULAR GENETICS, 2008, 17 :R122-R128

[8] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[9] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[10] New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk [J].

Dupuis, Josee ;

Langenberg, Claudia ;

Prokopenko, Inga ;

Saxena, Richa ;

Soranzo, Nicole ;

Jackson, Anne U. ;

Wheeler, Eleanor ;

Glazer, Nicole L. ;

Bouatia-Naji, Nabila ;

Gloyn, Anna L. ;

Lindgren, Cecilia M. ;

Magi, Reedik ;

Morris, Andrew P. ;

Randall, Joshua ;

Johnson, Toby ;

Elliott, Paul ;

Rybin, Denis ;

Thorleifsson, Gudmar ;

Steinthorsdottir, Valgerdur ;

Henneman, Peter ;

Grallert, Harald ;

Dehghan, Abbas ;

Hottenga, Jouke Jan ;

Franklin, Christopher S. ;

Navarro, Pau ;

Song, Kijoung ;

Goel, Anuj ;

Perry, John R. B. ;

Egan, Josephine M. ;

Lajunen, Taina ;

Grarup, Niels ;

Sparso, Thomas ;

Doney, Alex ;

Voight, Benjamin F. ;

Stringham, Heather M. ;

Li, Man ;

Kanoni, Stavroula ;

Shrader, Peter ;

Cavalcanti-Proenca, Christine ;

Kumari, Meena ;

Qi, Lu ;

Timpson, Nicholas J. ;

Gieger, Christian ;

Zabena, Carina ;

Rocheleau, Ghislain ;

Ingelsson, Erik ;

An, Ping ;

O'Connell, Jeffrey ;

Luan, Jian'an ;

Elliott, Amanda .

NATURE GENETICS, 2010, 42 (02) :105-U32

← 1 2 3 4 →