Genetic Determinants of Sex Hormones in Qatari Population

Sex hormones are steroid hormones that play an indispensable role in the physiological and pathological processes of the body. Genome-wide association studies (GWAS) have identified several genetic variants associated with serum levels of sex hormones. However, most GWAS has been extensively conducted in Caucasian populations, which makes it difficult to conclusively apply the results in other population groups, especially in the Qatari population.I conducted genome-wide association study using whole-genome sequence data from Qatar Genome Program (QGP) to detect genetic polymorphisms associated with serum levels of sex hormones: Testosterone (T), Estradiol (E), and sex hormone-binding globulin (SHBG). The discovery stage analysis was performed on 6,047 subjects, and I further did a replication GWAS of the results from the discovery stage in another set of subjects (n=7,768) from the same cohort (Qatar Biobank). For serum levels of T, we replicated one locus at 17p13.1 overlapping the SHBG gene. We also discovered a novel locus on chromosome 4p16.2 overlapping the anti-sense RNA gene STX18-AS1. This gene is known to be highly expressed in the testis. For serum levels of SHBG, we replicated two loci at the SHBG gene and JMJD1C gene. We also discovered a novel locus in chromosome 2q37.1 overlapping the protein-coding gene HDAC4. We didn’t find SNPs associated with estradiol at a genome-wide significance level. Further functional studies for the identified variants are needed to investigate the impact of genetic variants on serum levels of sex hormones and advance our understanding of molecular pathways involved in regulating them.