ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 979

Genome-Wide Association Study for Severe Radiographic Knee Osteoarthritis

Youfang Liu1, Michelle Yau2, Laura Yerges-Armstrong3, Braxton Mitchell3, Rebecca D. Jackson4, Marc C. Hochberg5, Shad Smith6, William Maixner6, Luda Diatchenko7 and Joanne M. Jordan8, 1Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, 2Epidemiology and Public Health, University of Maryland, Baltimore,, MD, 3Medicine, University of Maryland School of Medicine, Baltimore, MD, 4Division of Endocrinology, Diabetes, & Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH, 5Division of Rheumatology & Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, 6Regional Center for Neurosensory Disorders, School of Dentistry,, University of North Carolina, Chapel Hill, NC, 7McGill University, Montreal, QC, Canada, 8University of North Carolina Dept of Epidemiology, Chapel Hill, NC

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Genome

  • Tweet
  • Email
  • Print
Session Information

Session Title: Osteoarthritis

Session Type: Abstract Submissions (ARHP)

Background/Purpose

Knee osteoarthritis (OA) is a heritable common joint disorder. In previously reported genetic studies, cases were usually defined with a radiographic Kellgren and Lawrence (K/L) grade ≥2. Since more severe knee OA is more likely to have greater medical and public health impact, we searched for genetic variations associated with severe radiographic knee OA (rKOA) of K/L grade 3 or 4.

Methods

Caucasian participants with knee radiographic grade from the Johnston County Osteoarthritis Project (JoCo) were included in this analysis. Cases were defined as the subjects with KL grade ≥3 in at least one knee, while the controls were defined as the subjects with KL grades = 0 in both knees.   Genome wide genotyping was completed using the Illumina Infinium 1M-Duo array and imputed into 2.5M using HapMap II Caucasian as the reference data.  Genome-wide association analysis was performed using logistic regression with adjustment for age and sex, with and without additional adjustment for BMI.

Results

Of 672 participants [64% women, mean age = 64.2 (SD=10.6), mean BMI = 30.3(SD=6.4)], 353 were cases and 319 were controls. Although no SNPs reached genome-wide significant p-values at 5E-8, we identified two SNPs with p-values less than E-06 in the model without BMI adjustment (table). After BMI adjustment, associations were attenuated but still statistically significant (table). Both SNPs, rs11196174 and rs11196175, are located in the TCF7L2 gene which encodes a T-cell specific transcription factor participating in the Wnt signaling pathway, which has been shown to be related to OA. 

Conclusion: Two SNPs, rs11196174 and rs11196175, located in the TCF7L2 gene were associated with severe rKOA, supporting the possibility that the pathogenesis of severe rKOA may be through the Wnt signaling pathway. Further studies will need to validate this finding in other populations.

 

 

 

 

 

 

 

 

W/O BMI adjustment

With BMI adjustment

SNP

Gene

A1

A2

Freq1

Chr

Position

Beta

P-value

Beta

P-value

rs11196174

TCF7L2

A

G

0.69

10

114724086

0.82

5.4E-07

0.70

9.2e-05

rs11196175

TCF7L2

C

T

0.31

10

114726604

-0.81

3.9E-07

-0.71

6.0e-05

 


Disclosure:

Y. Liu,
None;

M. Yau,
None;

L. Yerges-Armstrong,
None;

B. Mitchell,
None;

R. D. Jackson,
None;

M. C. Hochberg,
None;

S. Smith,

Algynomics, Inc,

5;

W. Maixner,

Algynomics, Inc,

5;

L. Diatchenko,
None;

J. M. Jordan,

Algynomics,

5,

Samumed,

5,

Flexion,

5,

ClearView Healthcare Partners,

5,

Trinity Partners, LLC,

5.

  • Tweet
  • Email
  • Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/genome-wide-association-study-for-severe-radiographic-knee-osteoarthritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

© COPYRIGHT 2023 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences