Shared Genetic Architecture Between Rheumatoid Arthritis and Varying Osteoporotic Phenotypes

Melody Kasher, Maxim B. Freidin, Frances M.K. Williams, Stacey S. Cherny, Ida Malkin, Gregory Livshits*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Rheumatoid arthritis (RA) and low bone mineral density (BMD), an indicator of osteoporosis (OP), appear epidemiologically associated. Shared genetic factors may explain this association. This study aimed to investigate the presence of pleiotropy to clarify the potential genetic association between RA and OP. We examined BMDs at varying skeletal sites reported in UK Biobank as well as OP fracture acquired from the Genetic Factors for Osteoporosis (GEFOS) Consortium and the TwinsUK study. PRSice-2 was used to assess the potential shared genetic overlap between RA and OP. The presence of pleiotropy was examined using colocalization analysis. PRSice-2 revealed that RA was significantly associated with OP fracture (β = 351.6 ± 83.9, p value = 2.76E-05), total BMD (β = −1763.5 ± 612.8, p = 4.00E-03), spine BMD (β = −919.8 ± 264.6, p value = 5.09E-04), and forearm BMD (β = −66.09 ± 31.40, p value = 3.53E-02). Through colocalization analysis, the same causal genetic variants, associated with both RA and OP, were apparent in 12 genes: PLCL1, BOLL, AC011997.1, TNFAIP3, RP11-158I9.1, CDK6, CHCHD4P2, RP11-505C13.1, PHF19, TRAF1, C5, and C11orf49 with moderate posterior probabilities (>50%). Pleiotropy is involved in the association between RA and OP phenotypes. These findings contribute to the understanding of disease mechanisms and provide insight into possible therapeutic advancements and enhanced screening measures.

Original languageEnglish
Pages (from-to)440-453
Number of pages14
JournalJournal of Bone and Mineral Research
Issue number3
StatePublished - Mar 2022


FundersFunder number
Ariel University Research & Development Department2000000457
Israeli Ministry of Aliyah
Israeli Ministry of Aliyah and Integration
Wellcome Trust
Medical Research Council
National Institute for Health Research
European Commission
Israel Science Foundation2054/19
Sackler Faculty of Medicine, Tel-Aviv University18219




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