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Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19.
Ann Rheum Dis. 2007 May; 66(5):623-7.AR

Abstract

BACKGROUND AND OBJECTIVE

Until recently, there has been little agreement between conflicting results of osteoarthritis (OA) linkage. The purpose of this study was to conduct a whole-genome linkage scan to identify susceptibility loci for idiopathic hand OA in a large, population-based sample of females.

METHODS

Two OA-related radiographic phenotypes DIP (distal interphalangeal joints)-OA and Tot-KL (Kellgren-Lawrence score for both hands) chosen a priori were examined on 538 (269 pairs) monozygous and 1256 (628 pairs) dizygous (DZ) females. A genome-wide scan using microsatellite markers spaced 10 cM apart was performed on 1028 DZ twins. First, the heritability of the two OA phenotypes was estimated. Next, multipoint linkage analysis was conducted using a modified version of the Haseman-Elston method in a generalised linear model.

RESULTS

Heritability for DIP-OA and Tot-KL was found to be 47.6% and 67.4%, respectively. A genome-wide scan produced reliable evidence of significant linkage of DIP-OA on chromosome 2 at 90 cM (logarithmic odds ratio (LOD) = 2.90) and for Tot-KL on chromosome 19 at 65 cM (LOD = 4.26). These results are in agreement with data published previously. Several other significant linkage peaks were observed-for example, on chromosome 1 at 250 cM and on chromosome 3 at 30 cM-but were confirmed less reliably.

CONCLUSION

This is one of the largest OA linkage studies performed to date and provides clear evidence for linkage at two quantitative trait loci (on chromosome 2 at 90 cM and on chromosome 19 at 65 cM). As the results were robust and replicated in previous smaller studies, the fine mapping of these regions is a logical next step to pinpoint potential susceptibility gene(s) of interest.

Authors+Show Affiliations

Tel Aviv University, Tel Aviv, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

17127684

Citation

Livshits, Gregory, et al. "Genomewide Linkage Scan of Hand Osteoarthritis in Female Twin Pairs Showing Replication of Quantitative Trait Loci On Chromosomes 2 and 19." Annals of the Rheumatic Diseases, vol. 66, no. 5, 2007, pp. 623-7.
Livshits G, Kato BS, Zhai G, et al. Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19. Ann Rheum Dis. 2007;66(5):623-7.
Livshits, G., Kato, B. S., Zhai, G., Hart, D. J., Hunter, D., MacGregor, A. J., Williams, F. M., & Spector, T. D. (2007). Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19. Annals of the Rheumatic Diseases, 66(5), 623-7.
Livshits G, et al. Genomewide Linkage Scan of Hand Osteoarthritis in Female Twin Pairs Showing Replication of Quantitative Trait Loci On Chromosomes 2 and 19. Ann Rheum Dis. 2007;66(5):623-7. PubMed PMID: 17127684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19. AU - Livshits,Gregory, AU - Kato,Bernet S, AU - Zhai,Guangju, AU - Hart,Deborah J, AU - Hunter,David, AU - MacGregor,Alex J, AU - Williams,Frances M K, AU - Spector,Tim D, Y1 - 2006/11/24/ PY - 2006/11/28/pubmed PY - 2007/5/24/medline PY - 2006/11/28/entrez SP - 623 EP - 7 JF - Annals of the rheumatic diseases JO - Ann Rheum Dis VL - 66 IS - 5 N2 - BACKGROUND AND OBJECTIVE: Until recently, there has been little agreement between conflicting results of osteoarthritis (OA) linkage. The purpose of this study was to conduct a whole-genome linkage scan to identify susceptibility loci for idiopathic hand OA in a large, population-based sample of females. METHODS: Two OA-related radiographic phenotypes DIP (distal interphalangeal joints)-OA and Tot-KL (Kellgren-Lawrence score for both hands) chosen a priori were examined on 538 (269 pairs) monozygous and 1256 (628 pairs) dizygous (DZ) females. A genome-wide scan using microsatellite markers spaced 10 cM apart was performed on 1028 DZ twins. First, the heritability of the two OA phenotypes was estimated. Next, multipoint linkage analysis was conducted using a modified version of the Haseman-Elston method in a generalised linear model. RESULTS: Heritability for DIP-OA and Tot-KL was found to be 47.6% and 67.4%, respectively. A genome-wide scan produced reliable evidence of significant linkage of DIP-OA on chromosome 2 at 90 cM (logarithmic odds ratio (LOD) = 2.90) and for Tot-KL on chromosome 19 at 65 cM (LOD = 4.26). These results are in agreement with data published previously. Several other significant linkage peaks were observed-for example, on chromosome 1 at 250 cM and on chromosome 3 at 30 cM-but were confirmed less reliably. CONCLUSION: This is one of the largest OA linkage studies performed to date and provides clear evidence for linkage at two quantitative trait loci (on chromosome 2 at 90 cM and on chromosome 19 at 65 cM). As the results were robust and replicated in previous smaller studies, the fine mapping of these regions is a logical next step to pinpoint potential susceptibility gene(s) of interest. SN - 0003-4967 UR - https://www.unboundmedicine.com/medline/citation/17127684/Genomewide_linkage_scan_of_hand_osteoarthritis_in_female_twin_pairs_showing_replication_of_quantitative_trait_loci_on_chromosomes_2_and_19_ L2 - https://ard.bmj.com/lookup/pmidlookup?view=long&pmid=17127684 DB - PRIME DP - Unbound Medicine ER -