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Title: A novel common variant in DCST2 is associated with length in early life and height in adulthood
Authors: van der Valk, R. J. P.
Kreiner-Møller, E.
Kooijman, M. N.
Guxens, M,
Stergiakouli, E.
Sääf, A.
Bradfield, J. P.
Geller, F.
Hayes, M. G.
Cousminer, D. L.
Körner, A.
Thiering, E.
Curtin, J. A.
Myhre, R.
Huikari, V.
Joro, R.
Kerkhof, M.
Warrington, N. M.
Pitkänen, N.
Ntalla, Ioanna
Horikoshi, M.
Veijola, R.
Freathy, R. M.
Teo, Y-Y.
Barton, S. J.
Evans, D. M.
Kemp, J. P.
St Pourcain, B.
Ring, S. M.
Smith, G. D.
Bergström, A.
Kull, I.
Hakonarson, H.
Mentch, F. D.
Bisgaard, H.
Chawes, B.
Stokholm, J.
Waage, J.
Eriksen, P.
Sevelsted, A.
Melbye, M.
van Duijn, C. M.
Medina-Gomez, C.
Hofman, A.
de Jongste, J. C.
Taal, H. R.
Uitterlinden, A. G.
Armstrong, L. L.
Eriksson, J.
Palotie, A.
Bustamante, M.
Estivill, X.
Gonzalez, J. R.
Llop, S.
Kiess, W.
Mahajan, A.
Flexeder, C.
Tiesler, C. M. T.
Murray, C. S.
Simpson, A.
Magnus, P.
Sengpiel, V.
Hartikainen, A-L.
Keinanen-Kiukaanniemi, S.
Lewin, A.
Da Silva Couto Alves, A.
Blakemore, A. I.
Buxton, J. L.
Kaakinen, M.
Rodriguez, A.
Sebert, S.
Vaarasmaki, M.
Lakka, T.
Lindi, V.
Gehring, U.
Postma, D. S.
Ang, W.
Newnham, J. P.
Lyytikäinen, L-P.
Pahkala, K.
Raitakari, O. T.
Panoutsopoulou, K.
Zeggini, E.
Boomsma, D. I.
Groen-Blokhuis, M.
Ilonen, J.
Franke, L.
Hirschhorn, J. N.
Pers, T. H.
Liang, L.
Huang, J.
Hocher, B.
Knip, M.
Saw, Seang-Mei
Holloway, J. W.
Melén, E.
Grant, S. F. A.
Feenstra, B.
Lowe, W. L.
Widén, E.
Sergeyev, E.
Grallert, H.
Custovic, A.
Jacobsson, B.
Jarvelin, M-R.
Atalay, M.
Koppelman, G. H.
Pennell, C. E.
Niinikoski, H.
Dedoussis, G. V.
Mccarthy, M. I.
Frayling, T. M.
Sunyer, J.
Timpson, N. J.
Rivadeneira, F.
Bønnelykke, K.
Jaddoe, V. W. V.
First Published: 3-Oct-2014
Publisher: Oxford University Press (OUP)
Citation: Human Molecular Genetics, 2015, Vol. 24, No. 4
Abstract: 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 seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine 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; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). 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.
DOI Link: 10.1093/hmg/ddu510
ISSN: 0964-6906
eISSN: 1460-2083
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( licenses/by/4.0/), which permits unrestricted reuse,distribution,and reproduction in any medium, provided the original work is properly cited.
Description: Supplementary Material is available at HMG online.
Appears in Collections:Published Articles, Dept. of Health Sciences

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