Detection and quantification of inbreeding depression for complex traits from SNP data.
Proc Natl Acad Sci U S A
; 114(32): 8602-8607, 2017 08 08.
Article
em En
| MEDLINE
| ID: mdl-28747529
ABSTRACT
Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in [Formula see text] participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between -2.3 and -5.2 phenotypic SDs for complete inbreeding; [Formula see text]). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desequilíbrio de Ligação
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Consanguinidade
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Característica Quantitativa Herdável
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Polimorfismo de Nucleotídeo Único
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Bases de Dados de Ácidos Nucleicos
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Modelos Genéticos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article