  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.
