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

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

41 Citations (Scopus)

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
Article numberddu510
Pages (from-to)1155-1168
Number of pages14
JournalHuman Molecular Genetics
Volume24
Issue number4
DOIs
Publication statusPublished - 15 Feb 2015
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Parturition
Genome
Cell Fusion
Genome-Wide Association Study
Osteoclasts
Growth
Fetal Development
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, & 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. [ddu510]. https://doi.org/10.1093/hmg/ddu510

A novel common variant in DCST2 is associated with length in early life and height in adulthood. / Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; for the Early Growth Genetics (EGG) Consortium.

In: Human Molecular Genetics, Vol. 24, No. 4, ddu510, 15.02.2015, p. 1155-1168.

Research output: Contribution to journalArticle

Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Genetic Investigation of ANthropometric Traits (GIANT) Consortium & 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, vol. 24, no. 4, ddu510, pp. 1155-1168. https://doi.org/10.1093/hmg/ddu510
Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, for the Early Growth Genetics (EGG) Consortium. A novel common variant in DCST2 is associated with length in early life and height in adulthood. Human Molecular Genetics. 2015 Feb 15;24(4):1155-1168. ddu510. https://doi.org/10.1093/hmg/ddu510
Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium ; Genetic Investigation of ANthropometric Traits (GIANT) Consortium ; for the Early Growth Genetics (EGG) Consortium. / A novel common variant in DCST2 is associated with length in early life and height in adulthood. In: Human Molecular Genetics. 2015 ; Vol. 24, No. 4. pp. 1155-1168.
@article{d270258634e54f11b8ccf3b78aa8ac03,
title = "A novel common variant in DCST2 is associated with length in early life and height in adulthood",
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.",
author = "{Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium} and {Genetic Investigation of ANthropometric Traits (GIANT) Consortium} and {for the Early Growth Genetics (EGG) Consortium} and {van der Valk}, {Ralf J.P.} and Eskil Kreiner-M{\o}ller and Kooijman, {Marjolein N.} and Mo{\'o}nica Guxens and Evangelia Stergiakouli and Annika S{\"a}{\"a}f and Bradfield, {Jonathan P.} and Frank Geller and {Geoffrey Hayes}, M. and Cousminer, {Diana L.} and Antje K{\"o}rner and Elisabeth Thiering and Curtin, {John A.} and Ronny Myhre and Ville Huikari and Raimo Joro and Marjan Kerkhof and Warrington, {Nicole M.} and Niina Pitk{\"a}nen and Ioanna Ntalla and Momoko Horikoshi and Riitta Veijola and Freathy, {Rachel M.} and Teo, {Yik Ying} and Barton, {Sheila J.} and Evans, {David M.} and Kemp, {John P.} and Pourcain, {Beate St} and Ring, {Susan M.} and Smith, {George Davey} and Anna Bergstr{\"o}m and Inger Kull and Hakon Hakonarson and Mentch, {Frank D.} and Hans Bisgaard and Bo Chawes and Jakob Stokholm and Johannes Waage and Patrick Eriksen and Astrid Sevelsted and Mads Melbye and {van Duijn}, {Cornelia M.} and Carolina Medina-Gomez and Albert Hofman and {de Jongste}, {Johan C.} and {Rob Taal}, H. and Uitterlinden, {Andr{\'e} G.} and Armstrong, {Loren L.} and Johan Eriksson and Estivill, {Xavier P.}",
year = "2015",
month = "2",
day = "15",
doi = "10.1093/hmg/ddu510",
language = "English",
volume = "24",
pages = "1155--1168",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - A novel common variant in DCST2 is associated with length in early life and height in adulthood

AU - Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium

AU - Genetic Investigation of ANthropometric Traits (GIANT) Consortium

AU - for the Early Growth Genetics (EGG) Consortium

AU - van der Valk, Ralf J.P.

AU - Kreiner-Møller, Eskil

AU - Kooijman, Marjolein N.

AU - Guxens, Moónica

AU - Stergiakouli, Evangelia

AU - Sääf, Annika

AU - Bradfield, Jonathan P.

AU - Geller, Frank

AU - Geoffrey Hayes, M.

AU - Cousminer, Diana L.

AU - Körner, Antje

AU - Thiering, Elisabeth

AU - Curtin, John A.

AU - Myhre, Ronny

AU - Huikari, Ville

AU - Joro, Raimo

AU - Kerkhof, Marjan

AU - Warrington, Nicole M.

AU - Pitkänen, Niina

AU - Ntalla, Ioanna

AU - Horikoshi, Momoko

AU - Veijola, Riitta

AU - Freathy, Rachel M.

AU - Teo, Yik Ying

AU - Barton, Sheila J.

AU - Evans, David M.

AU - Kemp, John P.

AU - Pourcain, Beate St

AU - Ring, Susan M.

AU - Smith, George Davey

AU - Bergström, Anna

AU - Kull, Inger

AU - Hakonarson, Hakon

AU - Mentch, Frank D.

AU - Bisgaard, Hans

AU - Chawes, Bo

AU - Stokholm, Jakob

AU - Waage, Johannes

AU - Eriksen, Patrick

AU - Sevelsted, Astrid

AU - Melbye, Mads

AU - van Duijn, Cornelia M.

AU - Medina-Gomez, Carolina

AU - Hofman, Albert

AU - de Jongste, Johan C.

AU - Rob Taal, H.

AU - Uitterlinden, André G.

AU - Armstrong, Loren L.

AU - Eriksson, Johan

AU - Estivill, Xavier P.

PY - 2015/2/15

Y1 - 2015/2/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84985023154&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84985023154&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu510

DO - 10.1093/hmg/ddu510

M3 - Article

VL - 24

SP - 1155

EP - 1168

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 4

M1 - ddu510

ER -