A novel common variant in DCST2 is associated with length in early life and height in adulthood.
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| 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. |
| Year of Publication | 2015
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| Journal | Hum Mol Genet
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| Volume | 24
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| Issue | 4
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| Pages | 1155-68
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| Date Published | 2015 Feb 15
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| ISSN | 1460-2083
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| URL | |
| DOI | 10.1093/hmg/ddu510
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| PubMed ID | 25281659
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| PubMed Central ID | PMC4447786
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| Grant list | R01 HD034242 / HD / NICHD NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
MC_UU_12013/3 / Medical Research Council / United Kingdom
MR/K014536/1 / Medical Research Council / United Kingdom
R01 HD034243 / HD / NICHD NIH HHS / United States
MR/K002449/1 / Medical Research Council / United Kingdom
U01 HG004424 / HG / NHGRI NIH HHS / United States
U01 NS047537 / NS / NINDS NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
G0601361 / Medical Research Council / United Kingdom
U01 HG004415 / HG / NHGRI NIH HHS / United States
102215 / Wellcome Trust / United Kingdom
N01ES75558 / ES / NIEHS NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
MC_PC_15018 / Medical Research Council / United Kingdom
R01 HD056465 / HD / NICHD NIH HHS / United States
MC_UP_A620_1017 / Medical Research Council / United Kingdom
MC_UU_12013/1 / Medical Research Council / United Kingdom
MC_UU_12013/4 / Medical Research Council / United Kingdom
R01 CA141688 / CA / NCI NIH HHS / United States
U01 HG004423 / HG / NHGRI NIH HHS / United States
MC_UU_12011/4 / Medical Research Council / United Kingdom
098381 / Wellcome Trust / United Kingdom
Wellcome Trust / United Kingdom
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