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

van der Valk, Ralf J P (author)
Kreiner-Møller, Eskil (author)
Kooijman, Marjolein N (author)
show more...
Guxens, Mònica (author)
Stergiakouli, Evangelia (author)
Sääf, Annika (author)
Bradfield, Jonathan P (author)
Geller, Frank (author)
Hayes, M Geoffrey (author)
Cousminer, Diana L (author)
Körner, Antje (author)
Thiering, Elisabeth (author)
Curtin, John A (author)
Myhre, Ronny (author)
Huikari, Ville (author)
Joro, Raimo (author)
Kerkhof, Marjan (author)
Warrington, Nicole M (author)
Pitkänen, Niina (author)
Ntalla, Ioanna (author)
Horikoshi, Momoko (author)
Veijola, Riitta (author)
Freathy, Rachel M (author)
Teo, Yik-Ying (author)
Barton, Sheila J (author)
Evans, David M (author)
Kemp, John P (author)
St Pourcain, Beate (author)
Ring, Susan M (author)
Davey Smith, George (author)
Bergström, Anna (author)
Kull, Inger (author)
Hakonarson, Hakon (author)
Mentch, Frank D (author)
Bisgaard, Hans (author)
Chawes, Bo (author)
Stokholm, Jakob (author)
Waage, Johannes (author)
Eriksen, Patrick (author)
Sevelsted, Astrid (author)
Melbye, Mads (author)
van Duijn, Cornelia M (author)
Medina-Gomez, Carolina (author)
Hofman, Albert (author)
de Jongste, Johan C (author)
Taal, H Rob (author)
Uitterlinden, André G (author)
Armstrong, Loren L (author)
Eriksson, Johan (author)
Palotie, Aarno (author)
Bustamante, Mariona (author)
Estivill, Xavier (author)
Gonzalez, Juan R (author)
Llop, Sabrina (author)
Kiess, Wieland (author)
Mahajan, Anubha (author)
Flexeder, Claudia (author)
Tiesler, Carla M T (author)
Murray, Clare S (author)
Simpson, Angela (author)
Magnus, Per (author)
Sengpiel, Verena (author)
Hartikainen, Anna-Liisa (author)
Keinanen-Kiukaanniemi, Sirkka (author)
Lewin, Alexandra (author)
Da Silva Couto Alves, Alexessander (author)
Blakemore, Alexandra I (author)
Buxton, Jessica L (author)
Kaakinen, Marika (author)
Rodriguez, Alina (author)
Sebert, Sylvain (author)
Vaarasmaki, Marja (author)
Lakka, Timo (author)
Lindi, Virpi (author)
Gehring, Ulrike (author)
Postma, Dirkje S (author)
Ang, Wei (author)
Newnham, John P (author)
Lyytikäinen, Leo-Pekka (author)
Pahkala, Katja (author)
Raitakari, Olli T (author)
Panoutsopoulou, Kalliope (author)
Zeggini, Eleftheria (author)
Boomsma, Dorret I (author)
Groen-Blokhuis, Maria (author)
Ilonen, Jorma (author)
Franke, Lude (author)
Hirschhorn, Joel N (author)
Pers, Tune H (author)
Liang, Liming (author)
Huang, Jinyan (author)
Hocher, Berthold (author)
Knip, Mikael (author)
Saw, Seang-Mei (author)
Holloway, John W (author)
Melén, Erik (author)
Grant, Struan F A (author)
Feenstra, Bjarke (author)
Lowe, William L (author)
Widén, Elisabeth (author)
Sergeyev, Elena (author)
Grallert, Harald (author)
Custovic, Adnan (author)
Jacobsson, Bo (author)
Jarvelin, Marjo-Riitta (author)
Atalay, Mustafa (author)
Koppelman, Gerard H (author)
Pennell, Craig E (author)
Niinikoski, Harri (author)
Dedoussis, George V (author)
Mccarthy, Mark I (author)
Frayling, Timothy M (author)
Sunyer, Jordi (author)
Timpson, Nicholas J (author)
Rivadeneira, Fernando (author)
Bønnelykke, Klaus (author)
Jaddoe, Vincent W V (author)
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 (publisher)
2015
2015
English.
In: Human Molecular Genetics. - 0964-6906. ; 24:4, 1155-68
  • swepub:Mat__t
Abstract Subject headings
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  • 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.

Subject headings

Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Medical Genetics  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska grundvetenskaper  (hsv)
Medicinsk genetik  (hsv)
Social Sciences  (hsv)
Psychology  (hsv)
Samhällsvetenskap  (hsv)
Psykologi  (hsv)

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van der Valk, Ra ...
Kreiner-Møller, ...
Kooijman, Marjol ...
Guxens, Mònica
Stergiakouli, Ev ...
Sääf, Annika
show more...
Bradfield, Jonat ...
Geller, Frank
Hayes, M Geoffre ...
Cousminer, Diana ...
Körner, Antje
Thiering, Elisab ...
Curtin, John A
Myhre, Ronny
Huikari, Ville
Joro, Raimo
Kerkhof, Marjan
Warrington, Nico ...
Pitkänen, Niina
Ntalla, Ioanna
Horikoshi, Momok ...
Veijola, Riitta
Freathy, Rachel ...
Teo, Yik-Ying
Barton, Sheila J
Evans, David M
Kemp, John P
St Pourcain, Bea ...
Ring, Susan M
Davey Smith, Geo ...
Bergström, Anna
Kull, Inger
Hakonarson, Hako ...
Mentch, Frank D
Bisgaard, Hans
Chawes, Bo
Stokholm, Jakob
Waage, Johannes
Eriksen, Patrick
Sevelsted, Astri ...
Melbye, Mads
van Duijn, Corne ...
Medina-Gomez, Ca ...
Hofman, Albert
de Jongste, Joha ...
Taal, H Rob
Uitterlinden, An ...
Armstrong, Loren ...
Eriksson, Johan
Palotie, Aarno
Bustamante, Mari ...
Estivill, Xavier
Gonzalez, Juan R
Llop, Sabrina
Kiess, Wieland
Mahajan, Anubha
Flexeder, Claudi ...
Tiesler, Carla M ...
Murray, Clare S
Simpson, Angela
Magnus, Per
Sengpiel, Verena
Hartikainen, Ann ...
Keinanen-Kiukaan ...
Lewin, Alexandra
Da Silva Couto A ...
Blakemore, Alexa ...
Buxton, Jessica ...
Kaakinen, Marika
Rodriguez, Alina
Sebert, Sylvain
Vaarasmaki, Marj ...
Lakka, Timo
Lindi, Virpi
Gehring, Ulrike
Postma, Dirkje S
Ang, Wei
Newnham, John P
Lyytikäinen, Leo ...
Pahkala, Katja
Raitakari, Olli ...
Panoutsopoulou, ...
Zeggini, Elefthe ...
Boomsma, Dorret ...
Groen-Blokhuis, ...
Ilonen, Jorma
Franke, Lude
Hirschhorn, Joel ...
Pers, Tune H
Liang, Liming
Huang, Jinyan
Hocher, Berthold
Knip, Mikael
Saw, Seang-Mei
Holloway, John W
Melén, Erik
Grant, Struan F ...
Feenstra, Bjarke
Lowe, William L
Widén, Elisabeth
Sergeyev, Elena
Grallert, Harald
Custovic, Adnan
Jacobsson, Bo
Jarvelin, Marjo- ...
Atalay, Mustafa
Koppelman, Gerar ...
Pennell, Craig E
Niinikoski, Harr ...
Dedoussis, Georg ...
Mccarthy, Mark I
Frayling, Timoth ...
Sunyer, Jordi
Timpson, Nichola ...
Rivadeneira, Fer ...
Bønnelykke, Klau ...
Jaddoe, Vincent ...
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