A novel common variant in DCST2 is associated with length in early life and height in adulthood

van der Valk, R. J. P. and Kreiner-Moller, E. and Kooijman, M. N. and Guxens, M. and Stergiakouli, E. and Saaf, A. and Bradfield, J. P. and Geller, F. and Hayes, M. G. and Cousminer, D. L. and Korner, A. and Thiering, E. and Curtin, J. A. and Myhre, R. and Huikari, V. and Joro, R. and Kerkhof, M. and Warrington, N. M. and Pitkanen, N. and Ntalla, I. and Horikoshi, M. and Veijola, R. and Freathy, R. M. and Teo, Y.-Y. and Barton, S. J. and Evans, D. M. and Kemp, J. P. and St Pourcain, B. and Ring, S. M. and Davey Smith, G. and Bergstrom, A. and Kull, I. and Hakonarson, H. and Mentch, F. D. and Bisgaard, H. and Chawes, B. and Stokholm, J. and Waage, J. and Eriksen, P. and Sevelsted, A. and Melbye, M. and van Duijn, C. M. and Medina-Gomez, C. and Hofman, A. and de Jongste, J. C. and Taal, H. R. and Uitterlinden, A. G. and Armstrong, L. L. and Eriksson, J. and Palotie, A. and Bustamante, M. and Estivill, X. and Gonzalez, J. R. and Llop, S. and Kiess, W. and Mahajan, A. and Flexeder, C. and Tiesler, C. M. T. and Murray, C. S. and Simpson, A. and Magnus, P. and Sengpiel, V. and Hartikainen, A.-L. and Keinanen-Kiukaanniemi, S. and Lewin, A. and Da Silva Couto Alves, A. and Blakemore, A. I. and Buxton, J. L. and Kaakinen, M. and Rodriguez, A. and Sebert, S. and Vaarasmaki, M. and Lakka, T. and Lindi, V. and Gehring, U. and Postma, D. S. and Ang, W. and Newnham, J. P. and Lyytikainen, L.-P. and Pahkala, K. and Raitakari, O. T. and Panoutsopoulou, K. and Zeggini, E. and Boomsma, D. I. and Groen-Blokhuis, M. and Ilonen, J. and Franke, L. and Hirschhorn, J. N. and Pers, T. H. and Liang, L. and Huang, J. and Hocher, B. and Knip, M. and Saw, S.-M. and Holloway, J. W. and Melen, E. and Grant, S. F. A. and Feenstra, B. and Lowe, W. L. and Widen, E. and Sergeyev, E. and Grallert, H. and Custovic, A. and Jacobsson, B. and Jarvelin, M.-R. and Atalay, M. and Koppelman, G. H. and Pennell, C. E. and Niinikoski, H. and Dedoussis, G. V. and Mccarthy, M. I. and Frayling, T. M. and Sunyer, J. and Timpson, N. J. and Rivadeneira, F. and Bonnelykke, K. and Jaddoe, V. W. V. (2015) A novel common variant in DCST2 is associated with length in early life and height in adulthood. Human Molecular Genetics, 24 (4). pp. 1155-1168. ISSN 0964-6906

Full content URL: http://dx.doi.org/10.1093/hmg/ddu510

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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.

Keywords:Human genetics, JCOpen
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Social Science > School of Psychology
ID Code:22921
Deposited On:02 Aug 2016 12:38

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