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

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van der Valk, Ralf J P (author)

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

Article/chapterEnglish2015

Publisher, publication year, extent ...

2014-10-03
Oxford University Press (OUP),2015

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LIBRIS-ID:oai:gup.ub.gu.se/261471
https://gup.ub.gu.se/publication/261471URI
https://doi.org/10.1093/hmg/ddu510DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-24414URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:130808568URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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 and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reproduktionsmedicin och gynekologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Obstetrics, Gynaecology and Reproductive Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
SAMHÄLLSVETENSKAP Psykologi hsv//swe
SOCIAL SCIENCES Psychology hsv//eng
Adaptor Proteins
Signal Transducing
genetics
metabolism
Adult
Age Factors
Alleles
Body Height
genetics
Computational Biology
Databases
Genetic
Genetic Association Studies
Genetic Variation
Genotype
Humans
Infant
Newborn
Membrane Proteins
genetics
metabolism
Phenotype
Polymorphism
Single Nucleotide
Quantitative Trait Loci
Quantitative Trait
Heritable
Reproducibility of Results

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Kreiner-Møller, Eskil (author)
Kooijman, Marjolein N (author)
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 MKarolinska Institutet (author)
Kemp, John P (author)
St Pourcain, Beate (author)
Ring, Susan M (author)
Davey Smith, George (author)
Bergström, AnnaKarolinska Institutet (author)
Kull, IngerKarolinska Institutet (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,1977Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xsenve (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, AlinaMittuniversitetet,Avdelningen för psykologi(Swepub:miun)alirod (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,1960Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xjacbo (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)
Karolinska InstitutetInstitutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi (creator_code:org_t)

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In:Human molecular genetics: Oxford University Press (OUP)24:4, s. 1155-681460-20830964-6906

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By the author/editor: 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, 1 ...; 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 ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Obstetrics Gynae ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

SOCIAL SCIENCES: SOCIAL SCIENCES; and Psychology

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