Indiana University-Purdue University Indianapolis (IUPUI) / 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. / 2 years
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/14327 |
| Date | 18 July 2017 |
| Creators | Mo, Daojun |
| Contributors | He, Chunyan, Tu, Wanzhu, Song, Yiqing, Stone, Cynthia S. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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