New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Momoko Horikoshi, Hanieh Yaghootkar, Dennis O Mook-Kanamori, Ulla Sovio, H Rob Taal, Branwen J Hennig, Jonathan P Bradfield, Beate St Pourcain, David M Evans, Pimphen Charoen, Marika Kaakinen, Diana L Cousminer, Terho Lehtimäki, Eskil Kreiner-Møller, Nicole M Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J Berry, Elisabeth Thiering, Thiemo PfabSheila J Barton, Beverley M Shields, Marjan Kerkhof, Elisabeth M van Leeuwen, Anthony J Fulford, Zoltán Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T Raitakari, Marie N Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M Salem, Karen A Jameson, Kaixin Zhou, Dorota M Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S Adair, Fowzan S Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Aaron Isaacs, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalNature Genetics
Volume45
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

Keywords

  • Adult
  • Birth Weight/genetics
  • Blood Pressure/genetics
  • Body Height/genetics
  • Diabetes Mellitus, Type 2/genetics
  • Female
  • Fetal Development/genetics
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Infant, Newborn
  • Male
  • Meta-Analysis as Topic
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci

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