Detecting inbreeding depression in structured populations

• 成果类型: Article
• 署名作者: Lavanchy, Eleonore; Weir, Bruce S.; Goudet, Jerome
• 署名单位: University of Lausanne; Swiss Institute of Bioinformatics; University of Lausanne; University of Washington; University of Washington Seattle
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10025
• DOI: 10.1073/pnas.2315780121
• 发表日期: 2024-05-07
• 关键词: model approach; mixed-model; traits; quantification; association; compute

摘要

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients (F) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different F and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on F based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator.