Heritability of complex traits in sub-populations experiencing bottlenecks and growth

Cameron S Taylor, Daniel J Lawson*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Populations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation based approach to identify the impact of the demographic processes of drift, expansion, and migration on the heritability of complex trait. We show that demography has considerable impact on complex traits. We then investigate the power to resolve heritability of complex traits in GWAS studies subjected to demographic effects. We find that demography is an important component for interpreting inference of complex traits and has a nuanced impact on the power of GWAS. We conclude that demographic histories need to be explicitly modelled to properly quantify the history of selection on a complex trait.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalJournal of Human Genetics
Volume69
Issue number7
Early online date8 Apr 2024
DOIs
Publication statusPublished - 1 Jul 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Humans
  • Genome-Wide Association Study/methods
  • Multifactorial Inheritance/genetics
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Genetics, Population
  • Quantitative Trait, Heritable
  • Computer Simulation
  • Phenotype
  • Selection, Genetic

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