Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians

Michelle S Yau; Laura M Yerges-Armstrong; Youfang Liu; Cora E Lewis; David J Duggan; Jordan B Renner; James Torner; David T Felson; Charles E McCulloch; C Kent Kwoh; Michael C Nevitt; Marc C Hochberg; Braxton D Mitchell; Joanne M Jordan; Rebecca D Jackson

doi:10.1002/art.39932

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Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians

Journal article

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Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians

Michelle S Yau, Laura M Yerges-Armstrong, Youfang Liu, Cora E Lewis, David J Duggan, Jordan B Renner, James Torner, David T Felson, Charles E McCulloch, C Kent Kwoh, …

Arthritis & rheumatology (Hoboken, N.J.), Vol.69(2), pp.343-351

02/2017

DOI: 10.1002/art.39932

PMCID: PMC5274579

PMID: 27696742

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Abstract

A major barrier to genetic studies of osteoarthritis (OA) is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from 4 well-characterized North American cohorts, and we performed replication analysis of previously reported OA loci. We performed meta-analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definite osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead meta-analysis variants (P ≤ 1 × 10 ) from stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis. Lead variants from stage 1, representing 49 unique loci, were analyzed in stage 2; none met genome-wide significance in the combined analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3) with nominal significance (P < 0.05), which was also our top finding in the combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.79-0.91], P = 3.02 × 10 ). We observed nominally significant associations (P < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI 1.04-1.21], P = 2.13 × 10 ), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 × 10 ). These findings provide suggestive evidence of a novel knee OA locus and confirm previously reported associations in GDF5, CHST11, and FTO.

North America

Genome-Wide Association Study

Arthrography

Humans

Middle Aged

Osteoarthritis, Knee - genetics

European Continental Ancestry Group

Female

Male

Aged

Osteoarthritis, Knee - diagnostic imaging

Case-Control Studies

Details

Title: Subtitle: Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians
Creators: Michelle S Yau - University of Maryland School of Medicine, Baltimore
Laura M Yerges-Armstrong - University of Maryland School of Medicine, Baltimore
Youfang Liu - University of North Carolina at Chapel Hill
Cora E Lewis - University of Alabama at Birmingham
David J Duggan - Translational Genomics Research Institute, Phoenix, Arizona
Jordan B Renner - University of North Carolina at Chapel Hill
James Torner - University of Iowa, Iowa City
David T Felson - Boston University School of Medicine, Boston, Massachusetts
Charles E McCulloch - University of California, San Francisco
C Kent Kwoh - University of Arizona, Tucson
Michael C Nevitt - University of California, San Francisco
Marc C Hochberg - University of Maryland School of Medicine and Veterans Administration Medical Center, Baltimore
Braxton D Mitchell - University of Maryland School of Medicine and Veterans Administration Medical Center, Baltimore
Joanne M Jordan - University of North Carolina at Chapel Hill
Rebecca D Jackson - The Ohio State University, Columbus
Resource Type: Journal article
Publication Details: Arthritis & rheumatology (Hoboken, N.J.), Vol.69(2), pp.343-351
DOI: 10.1002/art.39932
PMID: 27696742
PMCID: PMC5274579
NLM abbreviation: Arthritis Rheumatol
ISSN: 2326-5191
eISSN: 2326-5205
Publisher: United States
Grant note: U01 AG018947 / NIA NIH HHS U01 AG018832 / NIA NIH HHS RC2 AR058950 / NIAMS NIH HHS U01 AG019069 / NIA NIH HHS T32 AG023480 / NIA NIH HHS N01AR22261 / NIAMS NIH HHS R01 AG028359 / NIA NIH HHS P30 DK072488 / NIDDK NIH HHS N01AR22260 / NIAMS NIH HHS T32 AG000262 / NIA NIH HHS N01AR22259 / NIAMS NIH HHS P60 AR030701 / NIAMS NIH HHS N01AR22262 / NIAMS NIH HHS N01AR22258 / NHLBI NIH HHS P60 AR049465 / NIAMS NIH HHS U01 DP006266 / NCCDPHP CDC HHS ARRA NIH HHS U01 AG018820 / NIA NIH HHS
Language: English
Date published: 02/2017
Academic Unit: Epidemiology; Surgery; Injury Prevention Research Center; Neurosurgery
Record Identifier: 9983995136302771

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