Associations between traits (blood pressure and body height growth) and reproductive timing related genetic variants from genome-wide association studies

Abstract

Recent genome-wide association studies (GWAS) have identified many common genetic variants that are associated with women’s reproductive timing characteristics including ages at menarche and at natural menopause. However, the associations of these variants with other human health related phenotypes such as blood pressure, cancer, diabetes, obesity, and body height growth have not been well studied. No published studies to our knowledge have directly assessed the genetic influence of reproductive timing related variants on the aforementioned common traits. A better understanding of pleiotropic effects of these variants is important because it will help elucidate the precise mechanisms of common traits/diseases such as hypertension which have not been fully understood so far, and give clues for developing better solutions for disease prevention and treatment. We, therefore, conducted three studies to explore genetic variant effects on blood pressure and body height growth. In the first study, we analyzed data from a local cohort of 601 healthy adolescents from Indianapolis schools. Mixed effect model analysis revealed that 11 reproductive related single nucleotide polymorphisms (SNPs) were significantly associated with blood pressure in the study subjects. In order to assess if these genetic effects extended to the adult blood pressure, we performed the second study to investigate the genetic effect on blood pressure in adults. We used the summary statistics obtained from the two large international GWAS consortia, the Blood Pressure Consortium and the ReproGen Consortium. Bivariate analyses showed that more than 100 SNPs were associated with both blood pressure and reproductive timing. As the blood pressure development is closely related to somatic growth, we conducted the third study to exam the genetic effect of reproductive-timing related variants on the linear growth from the aforementioned local cohort. We identified 8 genetic variants significantly associated with the catch-up of linear growth in the study subjects. In conclusion, these three studies collectively provided evidence in support of the pleiotropic effects of the reproductive timing variants, suggesting the common genetic basis underlying the correlated traits. Future research is needed to validate the findings.