| Application: | 24983, Generating effective therapeutic hypotheses from genomic and hospital linkage data |
| Title: | Sex-specific genetic effects across biomarkers |
| Size: | 520 B |
| Archived: | 22 Jul 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
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Notes
We examined sex differences in the genetics of thirty-three blood and urine lab test levels (biomarkers) in the UK Biobank population. We built a Bayesian Mixture Model to estimate the fraction of genetic variance shared between men and women for a given trait and used an extension of this model to identify genetic variants with sex-specific effects. The majority of these biomarkers did not show sex-related effects, with the exception of testosterone. For testosterone, we found a large number of genetic variants that showed effects in males but not females and vice versa. We built models to predict testosterone level from genetics, and found that sex-specific models outperformed sex combined models. Additionally, we used the sex-specific genetic variants associated with testosterone to examine the relationship between testosterone and several phenotypic and disease traits. We found evidence for a relationship between testosterone and height, body mass index, waist and hip circumference, and type 2 diabetes. Overall, our results demonstrate that while sex has a limited role in most of the genetics of most of the lab tests we examined, it plays a large role in the genetics of testosterone.Application 24983
Generating effective therapeutic hypotheses from genomic and hospital linkage data
This proposal seeks access to UK Biobank data to support efforts to generate effect therapeutic hypotheses from genomic and hospital in-patient data. We have developed novel statistical methods to assess the impact of genetic variation across a broad range of disease outcomes. We plan to take advantage of the tree structure of the ICD-10 codes to improve inference. By doing so we hope to prioritize genetic effects that are consistent with a protective profile. This will result in a set of therapeutic hypotheses that academics, pharmaceutical companies, and the public may be able to pursue. The research we plan is in agreement with the stated aim of UK Biobank ?research intended to improve the prevention, diagnosis and treatment of illness and the promotion of health throughout society?. By communicating to the public the set of therapeutic hypotheses we can generate from the data that has been generated by UK Biobank we hope that this will expedite interest in drug development from these insights. We will combine assessments of genetic associations with the tree-structure of ICD-10 codes and apply new statistical learning techniques to the summary data. A special class of genetic variants that we will focus on are protein-truncating variants (PTVs), commonly referred to as loss-of-function variants. Scanning for protective PTVs has been a successful strategy. These protective genetic variants reveal a process that is safe (naturally occurs in healthy adults) and effective (proven to reduce risk of disease). The full cohort.
| Lead investigator: | Dr Stephen Montgomery |
| Lead institution: | Stanford University |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3663 | Sex-specific genetic effects across biomarkers | Flynn E et al. | 2021 | Eur J Hum Genet |
Enabling scientific discoveries that improve human health