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A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand

Objective A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all publish...

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Published in:Inflammation research 2015-06, Vol.64 (6), p.405-414
Main Authors: Zhang, Rui, Yao, Jianfeng, Xu, Peng, Ji, Baohu, Luck, James V., Chin, Brian, Lu, Shemin, Kelsoe, John R., Ma, Jie
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container_end_page 414
container_issue 6
container_start_page 405
container_title Inflammation research
container_volume 64
creator Zhang, Rui
Yao, Jianfeng
Xu, Peng
Ji, Baohu
Luck, James V.
Chin, Brian
Lu, Shemin
Kelsoe, John R.
Ma, Jie
description Objective A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity. Results Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10 -6 ). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23). Conclusions Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.
doi_str_mv 10.1007/s00011-015-0818-9
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Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity. Results Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10 -6 ). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23). Conclusions Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.</description><identifier>ISSN: 1023-3830</identifier><identifier>EISSN: 1420-908X</identifier><identifier>DOI: 10.1007/s00011-015-0818-9</identifier><identifier>PMID: 25894512</identifier><language>eng</language><publisher>Basel: Springer Basel</publisher><subject>Allergology ; Biomedical and Life Sciences ; Biomedicine ; Dermatology ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Growth Differentiation Factor 5 - genetics ; Growth Differentiation Factor 5 - physiology ; Hand ; Humans ; Immunology ; Neurology ; Original Research Paper ; Osteoarthritis - epidemiology ; Osteoarthritis - genetics ; Osteoarthritis - metabolism ; Osteoarthritis, Hip - epidemiology ; Osteoarthritis, Hip - genetics ; Osteoarthritis, Hip - metabolism ; Osteoarthritis, Knee - epidemiology ; Osteoarthritis, Knee - genetics ; Osteoarthritis, Knee - metabolism ; Pharmacology/Toxicology ; Rheumatology</subject><ispartof>Inflammation research, 2015-06, Vol.64 (6), p.405-414</ispartof><rights>Springer Basel 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</citedby><cites>FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25894512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Yao, Jianfeng</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Ji, Baohu</creatorcontrib><creatorcontrib>Luck, James V.</creatorcontrib><creatorcontrib>Chin, Brian</creatorcontrib><creatorcontrib>Lu, Shemin</creatorcontrib><creatorcontrib>Kelsoe, John R.</creatorcontrib><creatorcontrib>Ma, Jie</creatorcontrib><title>A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand</title><title>Inflammation research</title><addtitle>Inflamm. Res</addtitle><addtitle>Inflamm Res</addtitle><description>Objective A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity. Results Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10 -6 ). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23). Conclusions Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. 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Res</stitle><addtitle>Inflamm Res</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>64</volume><issue>6</issue><spage>405</spage><epage>414</epage><pages>405-414</pages><issn>1023-3830</issn><eissn>1420-908X</eissn><abstract>Objective A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity. Results Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10 -6 ). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23). Conclusions Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.</abstract><cop>Basel</cop><pub>Springer Basel</pub><pmid>25894512</pmid><doi>10.1007/s00011-015-0818-9</doi><tpages>10</tpages></addata></record>
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subjects Allergology
Biomedical and Life Sciences
Biomedicine
Dermatology
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Growth Differentiation Factor 5 - genetics
Growth Differentiation Factor 5 - physiology
Hand
Humans
Immunology
Neurology
Original Research Paper
Osteoarthritis - epidemiology
Osteoarthritis - genetics
Osteoarthritis - metabolism
Osteoarthritis, Hip - epidemiology
Osteoarthritis, Hip - genetics
Osteoarthritis, Hip - metabolism
Osteoarthritis, Knee - epidemiology
Osteoarthritis, Knee - genetics
Osteoarthritis, Knee - metabolism
Pharmacology/Toxicology
Rheumatology
title A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand
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