stronger for one sex compared to the other, a composite association may mask important relationships. Indeed, this has proven to be the case; a 2015 case/control candidate gene study of age-related macular degeneration (AMD) provided the first evidence of a disease association that is female-specific [25]. The analysis uncovered a SNP within the DAPL1 gene, rs17810398, which is associated with AMD at the genome-wide significance level in females (p = 2.6 × 10−8), but not in males (p = 0.382). rs17810398 had not been previously identified as associated with AMD in large GWAS. While the functional implications of this sex-specific association between rs17810398 and AMD risk are still unknown, a more recent study by the same group identified another sex-specific locus related to copy number variation in the complement component 4A gene, which had a strong protective effect in females [26]. Results such as these highlight the cost of not performing sex-specific analyses—that information valuable to the health of both sexes may remain undiscovered.
