Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis

被引：225

作者：

Zengini, Eleni ^{[1
,2
]}

Hatzikotoulas, Konstantinos ^{[3
]}

Tachmazidou, Ioanna ^{[3
,4
]}

Steinberg, Julia ^{[3
,5
]}

Hartwig, Fernando P. ^{[6
,7
]}

Southam, Lorraine ^{[3
,8
]}

Hackinger, Sophie ^{[3
]}

Boer, Cindy G. ^{[9
,10
]}

Styrkarsdottir, Unnur ^{[11
]}

Gilly, Arthur ^{[3
]}

Suveges, Daniel ^{[3
]}

Killian, Britt ^{[3
]}

Ingvarsson, Thorvaldur ^{[12
,13
,14
]}

Jonsson, Helgi ^{[13
,15
]}

Babis, George C. ^{[16
]}

McCaskie, Andrew ^{[17
]}

Uitterlinden, Andre G. ^{[9
,10
]}

van Meurs, Joyce B. J. ^{[9
,10
]}

Thorsteinsdottir, Unnur ^{[11
,13
]}

Stefansson, Kari ^{[11
,13
]}

Smith, George Davey ^{[18
,19
,20
]}

Wilkinson, Jeremy M. ^{[1
]}

Zeggini, Eleftheria ^{[3
]}

机构：

[1] Univ Sheffield, Dept Oncol & Metab, Sheffield, S Yorkshire, England

[2] Dromokaiteio Psychiat Hosp, Psychiat Dept 5, Athens, Greece

[3] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England

[4] Med Res Ctr, GSK, R&D Target Sci, Stevenage, Herts, England

[5] Canc Council NSW, Canc Res Div, Sydney, NSW, Australia

[6] Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil

[7] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England

[8] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[9] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[10] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[11] DeCODE Genet Amgen, Reykjavik, Iceland

[12] Akureyri Hosp, Dept Orthopaed Surg, Akureyri, Iceland

[13] Univ Iceland, Fac Med, Reykjavik, Iceland

[14] Univ Akureyri, Inst Hlth Sci, Akureyri, Iceland

[15] Natl Univ Hosp Iceland, Landspitali, Dept Med, Reykjavik, Iceland

[16] Natl & Kapodistrian Univ Athens, Konstantopouleio Gen Hosp, Dept Orthopaed Surg 2, Athens, Greece

[17] Univ Cambridge, Addenbrookes Hosp, Dept Surg, Div Trauma & Orthopaed Surg, Cambridge, England

[18] Univ Bristol, Populat Hlth Sci, Bristol, Avon, England

[19] Univ Hosp Bristol, NHS Fdn Trust, Bristol Biomed Res Ctr, Natl Inst Hlth Res, Bristol, Avon, England

[20] Univ Bristol, Bristol, Avon, England

来源：

NATURE GENETICS | 2018年 / 50卷 / 04期

基金：

英国惠康基金;

关键词：

TRANSFORMING-GROWTH-FACTOR; CARTILAGE; MICE; BONE; P38; GDF5; RISK; CHONDROCYTES; ASSOCIATION; EXPRESSION;

D O I：

10.1038/s41588-018-0079-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

引用

页码：549 / +

页数：13

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