Document Detail


A novel common variant in DCST2 is associated with length in early life and height in adulthood.
MedLine Citation:
PMID:  25281659     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N=28,459). We identified 7 independent top SNPs (P<1x10(-6)) for birth length, of which 3 were novel and 4 were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The 3 novel SNPs were followed-up in 9 replication studies (Stage 2; N=11,995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1+2; ß=0.046, S.E.=0.008, P=2.46x10(-8), explained variance=0.05%). Rs905938 was also associated with infant length (N=28,228; P=5.54x10(-4)) and adult height (N=127,513; P=1.45x10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
Authors:
Ralf J P van der Valk; Eskil Kreiner-Møller; Marjolein N Kooijman; Mònica Guxens; Evangelia Stergiakouli; Annika Sääf; Jonathan P Bradfield; Frank Geller; M Geoffrey Hayes; Diana L Cousminer; Antje Körner; Elisabeth Thiering; John A Curtin; Ronny Myhre; Ville Huikari; Raimo Joro; Marjan Kerkhof; Nicole M Warrington; Niina Pitkänen; Ioanna Ntalla; Momoko Horikoshi; Riitta Veijola; Rachel M Freathy; Yik-Ying Teo; Sheila J Barton; David M Evans; John P Kemp; Beate St Pourcain; Susan M Ring; George Davey Smith; Anna Bergström; Inger Kull; Hakon Hakonarson; Frank D Mentch; Hans Bisgaard; Bo Chawes; Jakob Stokholm; Johannes Waage; Patrick Eriksen; Astrid Sevelsted; Mads Melbye; ; Cornelia M van Duijn; Carolina Medina-Gomez; Albert Hofman; Johan C de Jongste; H Rob Taal; André G Uitterlinden; ; Loren L Armstrong; Johan Eriksson; Aarno Palotie; Mariona Bustamante; Xavier Estivill; Juan R Gonzalez; Sabrina Llop; Wieland Kiess; Anubha Mahajan; Claudia Flexeder; Carla M T Tiesler; Clare S Murray; Angela Simpson; Per Magnus; Verena Sengpiel; Anna-Liisa Hartikainen; Sirkka Keinanen-Kiukaanniemi; Alexandra Lewin; Alexessander Da Silva Couto Alves; Alexandra I Blakemore; Jessica L Buxton; Marika Kaakinen; Alina Rodriguez; Sylvain Sebert; Marja Vaarasmaki; Timo Lakka; Virpi Lindi; Ulrike Gehring; Dirkje S Postma; Wei Ang; John P Newnham; Leo-Pekka Lyytikäinen; Katja Pahkala; Olli T Raitakari; Kalliope Panoutsopoulou; Eleftheria Zeggini; Dorret I Boomsma; Maria Groen-Blokhuis; Jorma Ilonen; Lude Franke; Joel N Hirschhorn; Tune H Pers; Liming Liang; Jinyan Huang; Berthold Hocher; Mikael Knip; Seang-Mei Saw; John W Holloway; Erik Melén; Struan F A Grant; Bjarke Feenstra; William L Lowe; Elisabeth Widén; Elena Sergeyev; Harald Grallert; Adnan Custovic; Bo Jacobsson; Marjo-Riitta Jarvelin; Mustafa Atalay; Gerard H Koppelman; Craig E Pennell; Harri Niinikoski; George V Dedoussis; Mark I McCarthy; Timothy M Frayling; Jordi Sunyer; Nicholas J Timpson; Fernando Rivadeneira; Klaus Bønnelykke; Vincent W V Jaddoe;
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-3
Journal Detail:
Title:  Human molecular genetics     Volume:  -     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-4     Completed Date:  -     Revised Date:  2014-10-5    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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