Open Problems in Human Trait Genetics

TL;DR

This paper reviews key unresolved challenges in human trait genetics, emphasizing analytical, conceptual, and technical issues that hinder full understanding of genetic influences on human traits.

Contribution

It provides a comprehensive overview of major open problems in the field, offering insights and directions for future research to address these challenges.

Findings

Identifies critical issues like population structure and gene-environment interactions.

Highlights data challenges including ethnic diversity and rare variants.

Discusses specific problems in heritability and polygenic risk scores.

Abstract

Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and opened the door for numerous breakthroughs in biology, medicine and other scientific fields. And yet, the ultimate promise of this area of research is still not fully realized. In this review, we highlight the major open problems that need to be solved to improve our understanding of the genetic variation underlying human traits, and by discussing these challenges provide a primer to the field. Our focus is on concrete analytical problems, both conceptual and technical in nature. We cover general issues in genetic studies such as population structure, epistasis and gene-environment interactions, data-related issues such as ethnic diversity and rare genetic variants, and specific challenges related to heritability estimates, genetic association studies and polygenic risk scores. We emphasize the interconnectedness of these open problems and suggest promising avenues to address them.