Genome-wide linkage scan of male sexual orientation. A. R. Sanders1,2, K. Dawood3, G. Rieger4, J. A. Badner2, E. S. Gershon2, R. S. Krishnappa5, A. B. Kolundzija6, S. Guo7, G. W. Beecham7, E. R. Martin7, J. M. Bailey8 1) NorthShore University HealthSystem, Evanston, IL; 2) University of Chicago, Chicago, IL; 3) Pennsylvania State University, University Park, PA; 4) Cornell University, Ithaca, NY; 5) East Tennessee State University, Johnson City, TN; 6) Columbia University, New York, NY; 7) University of Miami, Miami, FL; 8) Northwestern University, Evanston, IL.

   As with many other psychological traits, sexual orientation appears genetically complex, with important genetic and environmental factors. Family and twin studies have consistently demonstrated that genetic contributions are important for the development of sexual orientation in men. Previous research has found evidence for linkage to chromosome Xq28 in some studies focusing on pairs of homosexual brothers, but not in other such studies. To map loci for sexual orientation, and to appraise for potential replication of previous findings, we have conducted a genome-wide linkage scan using genotypes from the Affymetrix 5.0 SNP array on 410 independent pairs of homosexual brothers in 385 families, a sample set independent from previous studies. We classified subjects as homosexual based on both their self-reported sexual identity ("homosexual") and sexual feelings (Kinsey score of 5-6, indicating predominant or exclusive attraction to men). After rigorous quality control steps, we performed non-parametric linkage analysis using MERLIN. The strongest linkage peak, with multiple two-point LOD scores over 3.5 (maximum 4.0) and multipoint support, was in the pericentromeric region of chromosome 8, overlapping with the second strongest linkage peak in the next largest reported linkage scan of 155 independent pairs of homosexual brothers in 146 families. Our second strongest linkage region was on chromosome X with a maximum two-point LOD score of 2.65 at Xq28, the previously reported linkage region. Our findings, taken in context with previous work, suggest that genetic variation in each of these regions contributes to development of the important psychological trait of male sexual orientation.