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

van der Valk, Ralf J. P., Kreiner-Moller, Eskil, Kooijman, Marjolein N., Guxens, Monica, Stergiakouli, Evangelia, Saaf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Koerner, Antje, Thiering, Elisabeth, Curtin, John A., Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M., Pitkanen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M., Teo, Yik-Ying, Barton, Sheila J., Evans, David M., Kemp, John P., St Pourcain, Beate, Ring, Susan M., Smith, George Davey, Bergstrom, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M., Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C., Taal, H. Rob, Uitterlinden, Andre G., Armstrong, Loren L., Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R., Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M. T., Murray, Clare S., Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Alves, Alexessander Da Silva Couto, Blakemore, Alexandra I., Buxton, Jessica L., Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S., Ang, Wei, Newnham, John P., Lyytikainen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T., Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I., Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N., Pers, Tune H., Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W., Melen, Erik, Grant, Struan F. A., Feenstra, Bjarke, Lowe, William L., Widen, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H., Pennell, Craig E., Niinikoski, Harri, Dedoussis, George V., Mccarthy, Mark I., Frayling, Timothy M., Sunyer, Jordi, Timpson, Nicholas J., Rivadeneira, Fernando, Bonnelykke, Klaus, Jaddoe, Vincent W. V., Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Genetic Investigation of ANthropometric Traits (GIANT) Consortium and 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. doi:10.1093/hmg/ddu510


Author van der Valk, Ralf J. P.
Kreiner-Moller, Eskil
Kooijman, Marjolein N.
Guxens, Monica
Stergiakouli, Evangelia
Saaf, Annika
Bradfield, Jonathan P.
Geller, Frank
Hayes, M. Geoffrey
Cousminer, Diana L.
Koerner, Antje
Thiering, Elisabeth
Curtin, John A.
Myhre, Ronny
Huikari, Ville
Joro, Raimo
Kerkhof, Marjan
Warrington, Nicole M.
Pitkanen, Niina
Ntalla, Ioanna
Horikoshi, Momoko
Veijola, Riitta
Freathy, Rachel M.
Teo, Yik-Ying
Barton, Sheila J.
Evans, David M.
Kemp, John P.
St Pourcain, Beate
Ring, Susan M.
Smith, George Davey
Bergstrom, Anna
Kull, Inger
Hakonarson, Hakon
Mentch, Frank D.
Bisgaard, Hans
Chawes, Bo
Stokholm, Jakob
Waage, Johannes
Eriksen, Patrick
Sevelsted, Astrid
Melbye, Mads
van Duijn, Cornelia M.
Medina-Gomez, Carolina
Hofman, Albert
de Jongste, Johan C.
Taal, H. Rob
Uitterlinden, Andre G.
Armstrong, Loren L.
Eriksson, Johan
Palotie, Aarno
Bustamante, Mariona
Estivill, Xavier
Gonzalez, Juan R.
Llop, Sabrina
Kiess, Wieland
Mahajan, Anubha
Flexeder, Claudia
Tiesler, Carla M. T.
Murray, Clare S.
Simpson, Angela
Magnus, Per
Sengpiel, Verena
Hartikainen, Anna-Liisa
Keinanen-Kiukaanniemi, Sirkka
Lewin, Alexandra
Alves, Alexessander Da Silva Couto
Blakemore, Alexandra I.
Buxton, Jessica L.
Kaakinen, Marika
Rodriguez, Alina
Sebert, Sylvain
Vaarasmaki, Marja
Lakka, Timo
Lindi, Virpi
Gehring, Ulrike
Postma, Dirkje S.
Ang, Wei
Newnham, John P.
Lyytikainen, Leo-Pekka
Pahkala, Katja
Raitakari, Olli T.
Panoutsopoulou, Kalliope
Zeggini, Eleftheria
Boomsma, Dorret I.
Groen-Blokhuis, Maria
Ilonen, Jorma
Franke, Lude
Hirschhorn, Joel N.
Pers, Tune H.
Liang, Liming
Huang, Jinyan
Hocher, Berthold
Knip, Mikael
Saw, Seang-Mei
Holloway, John W.
Melen, Erik
Grant, Struan F. A.
Feenstra, Bjarke
Lowe, William L.
Widen, Elisabeth
Sergeyev, Elena
Grallert, Harald
Custovic, Adnan
Jacobsson, Bo
Jarvelin, Marjo-Riitta
Atalay, Mustafa
Koppelman, Gerard H.
Pennell, Craig E.
Niinikoski, Harri
Dedoussis, George V.
Mccarthy, Mark I.
Frayling, Timothy M.
Sunyer, Jordi
Timpson, Nicholas J.
Rivadeneira, Fernando
Bonnelykke, Klaus
Jaddoe, Vincent W. V.
Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium
Genetic Investigation of ANthropometric Traits (GIANT) Consortium
for the Early Growth Genetics (EGG) Consortium
Total Author Count Override 119
Title A novel common variant in DCST2 is associated with length in early life and height in adulthood
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
Publication date 2015-02-15
Year available 2014
Sub-type Article (original research)
DOI 10.1093/hmg/ddu510
Open Access Status
Volume 24
Issue 4
Start page 1155
End page 1168
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
1312 Molecular Biology
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 1 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 22 Apr 2015, 11:04:50 EST by Christopher O'Keefe on behalf of Scholarly Communication and Digitisation Service