Meta-analysis of Genome-Wide Linkage Studies of Atopic Dermatitis

Background. Atopic dermatitis (AD) is considered as a hereditary skin disease. Recently, a latest form of genetic research, genome-wide linkage study, has been carried out to detect its specific susceptibility genes. Since the results of these studies have been inconsistent, with linkage confirmed in different regions, we performed this meta-analysis. Objective: To assess heritability and identify chromosomal regions showing evidence of AD. Methods: A comprehensive and systematic search was conducted with PubMed databases. We combined results from three non-overlapping genome-wide linkage studies of AD, using the heterogeneity-based genome scan meta-analysis (HEGESMA) method, a rank-based analysis that assesses the strongest evidence for linkage within bins of a 30-centimorgan width on autosomes and the X chromosome. Results: The following ten bins had a p value of less than .05 in both weighted and unweighted analyses, suggesting that these bins contain AD-linked loci: 3.2, 3.4, 3.5, 4.5, 5.1, 5.2, 6.3, 9.2, 9.4, and 22.1. HEGESMA produced significant genome-wide evidence for linkage on 3p14.1-q12.3, with high average rank and low between-study heterogeneity; 5pter-p15.1 represents new significant loci not reported previously. Conclusion: HEGESMA confirms the region encoding CD80, CD86, and interleukins on chromosomes 3 and 5. The filaggrin gene (FLG) may be the susceptibility factor.