Genome-Wide Linkage Study Meta-Analysis of Male Sexual Orientation

Abstract

Male sexual orientation is a scientifically and socially important trait shown by family and twin studies to be influenced by environmental and complex genetic factors. Individual genome-wide linkage studies (GWLS) have been conducted, but not jointly analyzed. Two main datasets account for > 90% of the published GWLS concordant sibling pairs on the trait and are jointly analyzed here: MGSOSO (Molecular Genetic Study of Sexual Orientation; 409 concordant sibling pairs in 384 families, Sanders et al. (2015)) and Hamer (155 concordant sibling pairs in 145 families, Mustanski et al. (2005)). We conducted multipoint linkage analyses with Merlin on the datasets separately since they were genotyped differently, integrated genetic marker positions, and combined the resultant LOD (logarithm of the odds) scores at each 1 cM grid position. We continue to find the strongest linkage support at pericentromeric chromosome 8 and chromosome Xq28. We also incorporated the remaining published GWLS dataset (on 55 families) by using meta-analytic approaches on published summary statistics. The meta-analysis has maximized the positional information from GWLS of currently available family resources and can help prioritize findings from genome-wide association studies (GWAS) and other approaches. Although increasing evidence highlights genetic contributions to male sexual orientation, our current understanding of contributory loci is still limited, consistent with the complexity of the trait. Further increasing genetic knowledge about male sexual orientation, especially via large GWAS, should help advance our understanding of the biology of this important trait.

Keywords: Chromosome 8; Chromosome Xq28; Complex trait; Genome-wide linkage scan; Sexual orientation.

Fig. 1

Joint multipoint linkage analysis of the combined Hamer and MGSOSO datasets. Multipoint LOD scores are plotted v. the chromosomal positions for the nonparametric linkage analysis. Adjacent chromosomes are separated by alternating black and gray lines

Fig. 2

Individual chromosomal plots of multipoint linkage peaks on chromosomes 8 and X. Multipoint LOD scores are plotted v. the chromosomal positions for the nonparametric linkage analysis, the red line indicating the results from the Hamer dataset, the blue line for the MGSOSO dataset, and the black line for the joint analysis. Chromosome 8 (top) has its multipoint linkage peak in the pericentromeric region, and chromosome X (bottom) has its multipoint linkage peak at Xq28