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A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study.
Arthritis Rheum. 2004 Aug; 50(8):2489-96.AR

Abstract

OBJECTIVE

Studies investigating hand osteoarthritis (OA) as a single entity have not shown strong linkage of the disease with any chromosomal sites. We undertook this study to test our hypothesis that phenotypes of hand OA may show stronger linkage than has been shown for overall hand OA.

METHODS

We performed a factor analysis on measures of hand OA to determine patterns of disease. Using the joint regions identified by this analysis, we performed a genome-wide linkage analysis for OA susceptibility loci using 426 original cohort members and 790 offspring cohort members in 267 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence score, osteophytes, and joint space narrowing. Prior to linkage analysis, standardized residuals were computed from regression analysis of each phenotype on age. This was performed separately for each sex and cohort. The variance component model (GeneHunter) was then applied to the normalized scores of the residuals of both sexes and cohorts.

RESULTS

There was evidence suggestive of linkage (logarithm of odds [LOD] score >1.5) at 16 sites. Four of these sites had LOD scores >3.0. Two of these sites (identified in the full sample) included a linkage region for OA of the distal interphalangeal (DIP) joint on chromosome 7 (155 cM; LOD score 3.06) and a linkage region for OA of the first carpometacarpal (CMC) joint on chromosome 15 (81 cM; LOD score 6.25). The other 2 sites (identified in women) included a linkage region for OA of the DIP joint on chromosome 1 (202 cM; LOD score 3.03) and a linkage region for OA of the first CMC joint on chromosome 20 (4 cM; LOD score 3.74).

CONCLUSION

These data suggest that several chromosomes contain hand OA susceptibility genes and that a joint-specific approach may be more rewarding than a global approach to the genetics of hand OA. Further investigation of these regions is warranted using finer maps and other populations.

Authors+Show Affiliations

Hunter DJ
Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts 02118, USA. djhunter@bu.edu
Demissie S
No affiliation info available
Cupples LA
No affiliation info available
Aliabadi P
No affiliation info available
Felson DT
No affiliation info available

MeSH

Chromosome MappingChromosomes, Human, Pair 1Chromosomes, Human, Pair 20Chromosomes, Human, Pair 7Factor Analysis, StatisticalGenetic LinkageGenetic Predisposition to DiseaseHandHumansLod ScoreOsteoarthritisRadiography

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15334462

Citation

Hunter, D J., et al. "A Genome Scan for Joint-specific Hand Osteoarthritis Susceptibility: the Framingham Study." Arthritis and Rheumatism, vol. 50, no. 8, 2004, pp. 2489-96.
Hunter DJ, Demissie S, Cupples LA, et al. A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study. Arthritis Rheum. 2004;50(8):2489-96.
Hunter, D. J., Demissie, S., Cupples, L. A., Aliabadi, P., & Felson, D. T. (2004). A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study. Arthritis and Rheumatism, 50(8), 2489-96.
Hunter DJ, et al. A Genome Scan for Joint-specific Hand Osteoarthritis Susceptibility: the Framingham Study. Arthritis Rheum. 2004;50(8):2489-96. PubMed PMID: 15334462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study. AU - Hunter,D J, AU - Demissie,S, AU - Cupples,L A, AU - Aliabadi,P, AU - Felson,D T, PY - 2004/8/31/pubmed PY - 2004/9/25/medline PY - 2004/8/31/entrez SP - 2489 EP - 96 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 8 N2 - OBJECTIVE: Studies investigating hand osteoarthritis (OA) as a single entity have not shown strong linkage of the disease with any chromosomal sites. We undertook this study to test our hypothesis that phenotypes of hand OA may show stronger linkage than has been shown for overall hand OA. METHODS: We performed a factor analysis on measures of hand OA to determine patterns of disease. Using the joint regions identified by this analysis, we performed a genome-wide linkage analysis for OA susceptibility loci using 426 original cohort members and 790 offspring cohort members in 267 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence score, osteophytes, and joint space narrowing. Prior to linkage analysis, standardized residuals were computed from regression analysis of each phenotype on age. This was performed separately for each sex and cohort. The variance component model (GeneHunter) was then applied to the normalized scores of the residuals of both sexes and cohorts. RESULTS: There was evidence suggestive of linkage (logarithm of odds [LOD] score >1.5) at 16 sites. Four of these sites had LOD scores >3.0. Two of these sites (identified in the full sample) included a linkage region for OA of the distal interphalangeal (DIP) joint on chromosome 7 (155 cM; LOD score 3.06) and a linkage region for OA of the first carpometacarpal (CMC) joint on chromosome 15 (81 cM; LOD score 6.25). The other 2 sites (identified in women) included a linkage region for OA of the DIP joint on chromosome 1 (202 cM; LOD score 3.03) and a linkage region for OA of the first CMC joint on chromosome 20 (4 cM; LOD score 3.74). CONCLUSION: These data suggest that several chromosomes contain hand OA susceptibility genes and that a joint-specific approach may be more rewarding than a global approach to the genetics of hand OA. Further investigation of these regions is warranted using finer maps and other populations. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15334462/A_genome_scan_for_joint_specific_hand_osteoarthritis_susceptibility:_The_Framingham_Study_ DB - PRIME DP - Unbound Medicine ER -