Approved research

Decomposition of phenotype-dependent pleiotropic effects

Lay summary

The aim of this project is to know how genetic pleitropy could shape the evolution of human population. Pleiotropy refers to the phenomenon that a single gene can affect multiple seemingly unrelated traits. It is known that pleiotropy is common. For example, in humans the deficiency of phenylalanine hydroxylase causes mental retardation, eczema, and pigment defects; a quantitative trait analysis in mice found that each quantitative trait loci affected ~ on average eight skeletal characters. Because of pleiotropy, the effect of genetic loci on a given trait may be contingent on other phenotypes. For example, smoking or being overweight increases cancer risk of cancer driver mutations; baldness appears more often in male than in female. Therefore, it's difficult to understand pleiotropy by considering individual traits separately. Using the multi-dimensional omics data from UK Biobank, we can track the dynamics of allele frequency in multiple phenotypic backgrounds, by constructing and integrating the genotype-phenotype and phenotype-phenotype interaction network. We plan to finish the project within two years after we obtain the data. This study would provide novel insights into the co-occurrence or mutual-exclusiveness of diseases.