Genome-wide meta-analysis for rheumatoid arthritis

Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142-S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927-936, 2001; Jawaheer et al. in Arthritis Rheum 48:906-916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632-639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746-10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347-1363, 1996; Markianos et al. in Am J Hum Genet 68:963-977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142-S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P < 0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P < 0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.