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.
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: Stuart H Ralston; Nick Galwey; Ian MacKay; Omar M E Albagha; Lon Cardon; Juliet E Compston; Cyrus Cooper; Emma Duncan; Richard Keen; Bente Langdahl; Alastair McLellan; Jeffrey O'Riordan; Huibert A Pols; David M Reid; Andre G Uitterlinden; John Wass; Simon T Bennett Journal: Hum Mol Genet Date: 2005-03-03 Impact factor: 6.150
Authors: Eun-Kyung Suk; Ida Malkin; Stefan Dahm; Leonid Kalichman; Nico Ruf; Eugene Kobyliansky; Mohammad Toliat; Frank Rutsch; Peter Nürnberg; Gregory Livshits Journal: Arthritis Res Ther Date: 2005-07-13 Impact factor: 5.156
Authors: Annu Näkki; Sanna T Kouhia; Janna Saarela; Arsi Harilainen; Kaj Tallroth; Tapio Videman; Michele C Battié; Jaakko Kaprio; Leena Peltonen; Urho M Kujala Journal: BMC Med Genet Date: 2010-03-30 Impact factor: 2.103
Authors: Satu Hämäläinen; Svetlana Solovieva; Tapio Vehmas; Katariina Luoma; Päivi Leino-Arjas; Ari Hirvonen Journal: PLoS One Date: 2014-05-13 Impact factor: 3.240