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

2.50
Hdl Handle:
http://hdl.handle.net/11287/593943
Title:
A novel common variant in DCST2 is associated with length in early life and height in adulthood
Authors:
van der Valk, R. J.; Kreiner-Moller, E.; Kooijman, M. N.; Guxens, M.; Stergiakouli, E.; Saaf, A.; Bradfield, J. P.; Geller, F.; Hayes, M. G.; Cousminer, D. L.; Korner, A.; Thiering, E.; Curtin, J. A.; Myhre, R.; Huikari, V.; Joro, R.; Kerkhof, M.; Warrington, N. M.; Pitkanen, N.; Ntalla, I.; Horikoshi, M.; Veijola, R.; Freathy, Rachel M.; Teo, Y. Y.; Barton, S. J.; Evans, D. M.; Kemp, J. P.; St Pourcain, B.; Ring, S. M.; Davey Smith, G.; Bergstrom, A.; Kull, I.; Hakonarson, H.; Mentch, F. D.; Bisgaard, H.; Chawes, B.; Stokholm, J.; Waage, J.; Eriksen, P.; Sevelsted, A.; Melbye, M.; Early, Genetics; Lifecourse Epidemiology, Consortium; van Duijn, C. M.; Medina-Gomez, C.; Hofman, A.; de Jongste, J. C.; Taal, H. R.; Uitterlinden, A. G.; Genetic Investigation of, ANthropometric Traits Consortium; 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.; 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.; Lyytikainen, 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.; Melen, E.; Grant, S. F.; Feenstra, B.; Lowe, W. L.; Widen, 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, Timothy M.; Sunyer, J.; Timpson, N. J.; Rivadeneira, F.; Bonnelykke, K.; Jaddoe, V. W.; Early Growth Genetics, Consortium
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 x 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; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 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.
Citation:
Hum Mol Genet. 2015 Feb 15;24(4):1155-68.
Publisher:
Oxford Journals
Journal:
Human molecular genetics
Issue Date:
15-Feb-2015
URI:
http://hdl.handle.net/11287/593943
DOI:
10.1093/hmg/ddu510
PubMed ID:
25281659
Additional Links:
http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=25281659
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1460-2083
Appears in Collections:
2015 RD&E publications; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorvan der Valk, R. J.en
dc.contributor.authorKreiner-Moller, E.en
dc.contributor.authorKooijman, M. N.en
dc.contributor.authorGuxens, M.en
dc.contributor.authorStergiakouli, E.en
dc.contributor.authorSaaf, A.en
dc.contributor.authorBradfield, J. P.en
dc.contributor.authorGeller, F.en
dc.contributor.authorHayes, M. G.en
dc.contributor.authorCousminer, D. L.en
dc.contributor.authorKorner, A.en
dc.contributor.authorThiering, E.en
dc.contributor.authorCurtin, J. A.en
dc.contributor.authorMyhre, R.en
dc.contributor.authorHuikari, V.en
dc.contributor.authorJoro, R.en
dc.contributor.authorKerkhof, M.en
dc.contributor.authorWarrington, N. M.en
dc.contributor.authorPitkanen, N.en
dc.contributor.authorNtalla, I.en
dc.contributor.authorHorikoshi, M.en
dc.contributor.authorVeijola, R.en
dc.contributor.authorFreathy, Rachel M.en
dc.contributor.authorTeo, Y. Y.en
dc.contributor.authorBarton, S. J.en
dc.contributor.authorEvans, D. M.en
dc.contributor.authorKemp, J. P.en
dc.contributor.authorSt Pourcain, B.en
dc.contributor.authorRing, S. M.en
dc.contributor.authorDavey Smith, G.en
dc.contributor.authorBergstrom, A.en
dc.contributor.authorKull, I.en
dc.contributor.authorHakonarson, H.en
dc.contributor.authorMentch, F. D.en
dc.contributor.authorBisgaard, H.en
dc.contributor.authorChawes, B.en
dc.contributor.authorStokholm, J.en
dc.contributor.authorWaage, J.en
dc.contributor.authorEriksen, P.en
dc.contributor.authorSevelsted, A.en
dc.contributor.authorMelbye, M.en
dc.contributor.authorEarly, Geneticsen
dc.contributor.authorLifecourse Epidemiology, Consortiumen
dc.contributor.authorvan Duijn, C. M.en
dc.contributor.authorMedina-Gomez, C.en
dc.contributor.authorHofman, A.en
dc.contributor.authorde Jongste, J. C.en
dc.contributor.authorTaal, H. R.en
dc.contributor.authorUitterlinden, A. G.en
dc.contributor.authorGenetic Investigation of, ANthropometric Traits Consortiumen
dc.contributor.authorArmstrong, L. L.en
dc.contributor.authorEriksson, J.en
dc.contributor.authorPalotie, A.en
dc.contributor.authorBustamante, M.en
dc.contributor.authorEstivill, X.en
dc.contributor.authorGonzalez, J. R.en
dc.contributor.authorLlop, S.en
dc.contributor.authorKiess, W.en
dc.contributor.authorMahajan, A.en
dc.contributor.authorFlexeder, C.en
dc.contributor.authorTiesler, C. M.en
dc.contributor.authorMurray, C. S.en
dc.contributor.authorSimpson, A.en
dc.contributor.authorMagnus, P.en
dc.contributor.authorSengpiel, V.en
dc.contributor.authorHartikainen, A. L.en
dc.contributor.authorKeinanen-Kiukaanniemi, S.en
dc.contributor.authorLewin, A.en
dc.contributor.authorDa Silva Couto Alves, A.en
dc.contributor.authorBlakemore, A. I.en
dc.contributor.authorBuxton, J. L.en
dc.contributor.authorKaakinen, M.en
dc.contributor.authorRodriguez, A.en
dc.contributor.authorSebert, S.en
dc.contributor.authorVaarasmaki, M.en
dc.contributor.authorLakka, T.en
dc.contributor.authorLindi, V.en
dc.contributor.authorGehring, U.en
dc.contributor.authorPostma, D. S.en
dc.contributor.authorAng, W.en
dc.contributor.authorNewnham, J. P.en
dc.contributor.authorLyytikainen, L. P.en
dc.contributor.authorPahkala, K.en
dc.contributor.authorRaitakari, O. T.en
dc.contributor.authorPanoutsopoulou, K.en
dc.contributor.authorZeggini, E.en
dc.contributor.authorBoomsma, D. I.en
dc.contributor.authorGroen-Blokhuis, M.en
dc.contributor.authorIlonen, J.en
dc.contributor.authorFranke, L.en
dc.contributor.authorHirschhorn, J. N.en
dc.contributor.authorPers, T. H.en
dc.contributor.authorLiang, L.en
dc.contributor.authorHuang, J.en
dc.contributor.authorHocher, B.en
dc.contributor.authorKnip, M.en
dc.contributor.authorSaw, S. M.en
dc.contributor.authorHolloway, J. W.en
dc.contributor.authorMelen, E.en
dc.contributor.authorGrant, S. F.en
dc.contributor.authorFeenstra, B.en
dc.contributor.authorLowe, W. L.en
dc.contributor.authorWiden, E.en
dc.contributor.authorSergeyev, E.en
dc.contributor.authorGrallert, H.en
dc.contributor.authorCustovic, A.en
dc.contributor.authorJacobsson, B.en
dc.contributor.authorJarvelin, M. R.en
dc.contributor.authorAtalay, M.en
dc.contributor.authorKoppelman, G. H.en
dc.contributor.authorPennell, C. E.en
dc.contributor.authorNiinikoski, H.en
dc.contributor.authorDedoussis, G. V.en
dc.contributor.authorMcCarthy, M. I.en
dc.contributor.authorFrayling, Timothy M.en
dc.contributor.authorSunyer, J.en
dc.contributor.authorTimpson, N. J.en
dc.contributor.authorRivadeneira, F.en
dc.contributor.authorBonnelykke, K.en
dc.contributor.authorJaddoe, V. W.en
dc.contributor.authorEarly Growth Genetics, Consortiumen
dc.date.accessioned2016-01-19T12:37:46Zen
dc.date.available2016-01-19T12:37:46Zen
dc.date.issued2015-02-15en
dc.identifier.citationHum Mol Genet. 2015 Feb 15;24(4):1155-68.en
dc.identifier.issn1460-2083en
dc.identifier.pmid25281659en
dc.identifier.doi10.1093/hmg/ddu510en
dc.identifier.urihttp://hdl.handle.net/11287/593943en
dc.description.abstractCommon 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 x 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; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 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.en
dc.language.isoengen
dc.publisherOxford Journalsen
dc.relation.urlhttp://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=25281659en
dc.titleA novel common variant in DCST2 is associated with length in early life and height in adulthooden
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalHuman molecular geneticsen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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