A genome scan for parent-of-origin linkage effects in alcoholism

Abstract Background Alcoholism is a complex disease in which genomic imprinting may play an important role in its susceptibility. Objective To conduct a genome-wide search for loci that may have strong parent-of-origin linkage effects in alcoholism; to compare the linkage results between the microsatellites and the two single-nucleotide polymorphism (SNP) platforms. Methods Nonparametric linkage analyses were performed using ALLEGRO with the three sets of markers provided by the Genetic Analysis Workshop 14 for the Collaborative Study on the Genetics of Alcoholism Problem 1 data. Both sex-averaged and sex-specific genetic maps were used. We also provided a valid statistical test to determine whether the parental allele sharing differed significantly. Results Significant maternal linkage effects (paternal imprinting) were observed on chromosome 12 using either the microsatellite markers or the two SNP panels. The two SNP sets did not improve the linkage signals compared to the results from the microsatellite markers on chromosome 12. Possible paternal linkage effects (maternal imprinting) on chromosome 7 and maternal linkage effects (paternal imprinting) on chromosome 10 were found using the two SNP panels. Conclusion For diseases which may have parent-of-origin effects, linkage analysis looking at parental sharing separately may reduce locus heterogeneity and increase the ability to identify that which can not be identified with usual linkage analysis