You are here: Home Publications A novel common variant in DCST2 is associated with length in early life and height in adulthood

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

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, I., 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., Davey Smith, G., 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, S.-M., 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., & Early Growth Genetics (EGG) Consortium (2015). A novel common variant in DCST2 is associated with length in early life and height in adulthood. Human Molecular Genetics, 24(4), 1155-1168. doi:10.1093/hmg/ddu510.
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.
About MPI

This is the MPI

The Max Planck Institute for Psycholinguistics is an institute of the German Max Planck Society. Our mission is to undertake basic research into the psychological,social and biological foundations of language. The goal is to understand how our minds and brains process language, how language interacts with other aspects of mind, and how we can learn languages of quite different types.

The institute is situated on the campus of the Radboud University. We participate in the Donders Institute for Brain, Cognition and Behaviour, and have particularly close ties to that institute's Centre for Cognitive Neuroimaging. We also participate in the Centre for Language Studies. A joint graduate school, the IMPRS in Language Sciences, links the Donders Institute, the CLS and the MPI.

 

Street address
Wundtlaan 1
6525 XD Nijmegen
The Netherlands


Mailing address
P.O. Box 310
6500 AH Nijmegen
The Netherlands

Phone:   +31-24-3521911
Fax:        +31-24-3521213
E-mail:   


Public Outreach Officer
Charlotte Horn