Open problems in human trait genetics

Nadav Brandes; Omer Weissbrod; Michal Linial

doi:10.1186/s13059-022-02697-9

Open problems in human trait genetics

Nadav Brandes^*, Omer Weissbrod, Michal Linial

^*Corresponding author for this work

Department of Biological Chemistry

Research output: Contribution to journal › Review article › peer-review

9 Scopus citations

Abstract

Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and yet, the genetics of most traits is still poorly understood. In this review, we highlight the major open problems that need to be solved, and by discussing these challenges provide a primer to the field. We cover general issues such as population structure, epistasis and gene-environment interactions, data-related issues such as ancestry 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 problems and suggest promising avenues to address them.

Original language	American English
Article number	131
Journal	Genome Biology
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13059-022-02697-9
State	Published - Dec 2022

Bibliographical note

Funding Information:
Publication fees were covered in part by the ISF grant number: 2753/20 (to M.L.).

Funding Information:
We would like to thank Alexander (Sasha) Gusev, Alexander l. Young, Noah Zaitlen, Or Zuk, Sagiv Shifman, Shai Ben-Shahar, Shai Carmi, Shiri Shakedi, Regev Schweiger, and Yossi Farjoun for offering us their perspectives on open problems in the field. This review does not necessarily reflect their views, and all mistakes are ours. We also thank Vladimir Gritsenko and Yedael Y. Waldman for valuable feedback on our initial draft. The review history is available as Additional file 1. Andrew Cosgrove was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Causal variants
Complex human traits
Diversity
Epistatis
GWAS
Gene-environment interactions
Genome-wide association studies
GxE
GxG
Heritability
Human phenotypes
Linkage disequilibrium
Missing heritability
Non-additive genetic effects
PRS
Polygenic risk scores
Population structure
Rare variants
Recessive effects
Statistical genetics

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10.1186/s13059-022-02697-9

Cite this

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title = "Open problems in human trait genetics",

abstract = "Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and yet, the genetics of most traits is still poorly understood. In this review, we highlight the major open problems that need to be solved, and by discussing these challenges provide a primer to the field. We cover general issues such as population structure, epistasis and gene-environment interactions, data-related issues such as ancestry 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 problems and suggest promising avenues to address them.",

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author = "Nadav Brandes and Omer Weissbrod and Michal Linial",

note = "Funding Information: Publication fees were covered in part by the ISF grant number: 2753/20 (to M.L.). Funding Information: We would like to thank Alexander (Sasha) Gusev, Alexander l. Young, Noah Zaitlen, Or Zuk, Sagiv Shifman, Shai Ben-Shahar, Shai Carmi, Shiri Shakedi, Regev Schweiger, and Yossi Farjoun for offering us their perspectives on open problems in the field. This review does not necessarily reflect their views, and all mistakes are ours. We also thank Vladimir Gritsenko and Yedael Y. Waldman for valuable feedback on our initial draft. The review history is available as Additional file 1. Andrew Cosgrove was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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N2 - Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and yet, the genetics of most traits is still poorly understood. In this review, we highlight the major open problems that need to be solved, and by discussing these challenges provide a primer to the field. We cover general issues such as population structure, epistasis and gene-environment interactions, data-related issues such as ancestry 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 problems and suggest promising avenues to address them.

AB - Genetic studies of human traits have revolutionized our understanding of the variation between individuals, and yet, the genetics of most traits is still poorly understood. In this review, we highlight the major open problems that need to be solved, and by discussing these challenges provide a primer to the field. We cover general issues such as population structure, epistasis and gene-environment interactions, data-related issues such as ancestry 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 problems and suggest promising avenues to address them.

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KW - Linkage disequilibrium

KW - Missing heritability

KW - Non-additive genetic effects

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KW - Population structure

KW - Rare variants

KW - Recessive effects

KW - Statistical genetics

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Open problems in human trait genetics

Abstract

Bibliographical note

Keywords

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