Approved Research

Sex-differences in genetic architecture of complex traits and diseases in humans

Lay summary

Rationale

Sex-differences in human traits is widespread and is especially common in onset, prevalence or expression of diseases.  E.g., cardiovascular diseases, schizophrenia, autism etc. Human traits like waist to hip ratio, lipid levels also vary between the sexes. Though this observation of differences is common, neither it is clear how such differences can evolve, nor the underlying genetics of the difference is known. Sex-specificity can be at the genetic level, i.e., different genes are involved in males and females for the same trait or the expression of the same genes, i.e., the post-processing of the product of the genes are different in the sexes. Genetic correlation is the estimation of the degree to which the underlying genetic bases of traits covary with each other. One way to investigate sex-differences is to estimate the genetic correlation between sexes for the same trait. A high correlation will indicate similarity of underlying genetic structure between the sexes, while a low correlation will indicate difference. In human genetics, most of the work done on sex-difference till now focuses on difference for a single trait. But traits do not occur in isolation, and functionally related traits covary. E.g., incidence of coronary artery disease, lipid levels are correlated, and studying one trait in isolation will not give a true picture of the underlying biology. Hence, studying these traits together will offer a more realistic perspective on human diseases. The theory behind such multi-trait analyses has been worked out quite early and is regularly practised in case of non-human animals. It is surprising that such analyses are not implemented in humans yet, though in humans larger sample sizes are available.

Aim

The main aim of the project is to study the underlying genetic basis of differences in traits and diseases between the sexes. Analyses using multiple functionally related traits together for both the sexes will be done.

The duration of the project is for three years.

Public health impact

1) This work will help to recognize the sex-differential effects of risk factors affecting various diseases. This will help the medical professionals to identify the risks early on and to provide precision health care.

2) This study can have deep implications in tailoring sex-specific precision medicine. Drugs and dosages that work for males might not be effective in case of females, and hence information on sex-specificity will improve the accuracy with which patients are classified and treated.