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

Ralf J P van der Valk, Eskil Kreiner-Møller, Marjolein N. Kooijman, Moónica 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 NtallaMomoko 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, William L. Lowe, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, for the Early Growth Genetics (EGG) Consortium

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1155-1168
Number of pages14
JournalHuman molecular genetics
Volume24
Issue number4
DOIs
StatePublished - Feb 15 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'A novel common variant in DCST2 is associated with length in early life and height in adulthood'. Together they form a unique fingerprint.

  • Cite this

    van der Valk, R. J. P., Kreiner-Møller, E., Kooijman, M. N., Guxens, M., Stergiakouli, E., Sääf, A., Bradfield, J. P., Geller, F., Geoffrey Hayes, M., Cousminer, D. L., Körner, A., Thiering, E., Curtin, J. A., Myhre, R., Huikari, V., Joro, R., Kerkhof, M., Warrington, N. M., Pitkänen, N., ... for the 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. https://doi.org/10.1093/hmg/ddu510