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Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.

作者信息

Soranzo Nicole, Rivadeneira Fernando, Chinappen-Horsley Usha, Malkina Ida, Richards J Brent, Hammond Naomi, Stolk Lisette, Nica Alexandra, Inouye Michael, Hofman Albert, Stephens Jonathan, Wheeler Eleanor, Arp Pascal, Gwilliam Rhian, Jhamai P Mila, Potter Simon, Chaney Amy, Ghori Mohammed J R, Ravindrarajah Radhi, Ermakov Sergey, Estrada Karol, Pols Huibert A P, Williams Frances M, McArdle Wendy L, van Meurs Joyce B, Loos Ruth J F, Dermitzakis Emmanouil T, Ahmadi Kourosh R, Hart Deborah J, Ouwehand Willem H, Wareham Nicholas J, Barroso Inês, Sandhu Manjinder S, Strachan David P, Livshits Gregory, Spector Timothy D, Uitterlinden André G, Deloukas Panos

机构信息

Human Genetics Department, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

出版信息

PLoS Genet. 2009 Apr;5(4):e1000445. doi: 10.1371/journal.pgen.1000445. Epub 2009 Apr 3.


DOI:10.1371/journal.pgen.1000445
PMID:19343178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2661236/
Abstract

Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8) and rs910316 in TMED10, P-value = 1.4x10(-7)) and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7) and rs849141 in JAZF1, P-value = 3.2x10(-11)). One locus (rs1182188 at GNA12) identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk) and lower-body (hip axis and femur) skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5) and rs6817306 in LCORL, P-value = 4x10(-4)), hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4) and rs4911494 at UQCC, P-value = 1.9x10(-4)), and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5) and rs10946808 at HIST1H1D, P-value = 6.4x10(-6)). Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/291f/2661236/be8fb45e4b80/pgen.1000445.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/291f/2661236/be8fb45e4b80/pgen.1000445.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/291f/2661236/be8fb45e4b80/pgen.1000445.g001.jpg

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本文引用的文献

[1]
Reverse engineering the genotype-phenotype map with natural genetic variation.

Nature. 2008-12-11

[2]
Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis.

Hum Mol Genet. 2009-1-15

[3]
Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees.

Arthritis Rheum. 2008-6

[4]
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.

Lancet. 2008-5-3

[5]
Common variants near MC4R are associated with fat mass, weight and risk of obesity.

Nat Genet. 2008-6

[6]
Genome-wide association analysis identifies 20 loci that influence adult height.

Nat Genet. 2008-5

[7]
Many sequence variants affecting diversity of adult human height.

Nat Genet. 2008-5

[8]
Identification of ten loci associated with height highlights new biological pathways in human growth.

Nat Genet. 2008-5

[9]
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

Nat Genet. 2008-5

[10]
A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility.

Hum Mol Genet. 2008-5-15

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