--- res: bibo_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 ∼140,000 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; P<0.001). 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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Loic foaf_name: Yengo, Loic foaf_surname: Yengo - foaf_Person: foaf_givenName: Zhihong foaf_name: Zhu, Zhihong foaf_surname: Zhu - foaf_Person: foaf_givenName: Naomi R. foaf_name: Wray, Naomi R. foaf_surname: Wray - foaf_Person: foaf_givenName: Bruce S. foaf_name: Weir, Bruce S. foaf_surname: Weir - foaf_Person: foaf_givenName: Jian foaf_name: Yang, Jian foaf_surname: Yang - foaf_Person: foaf_givenName: Matthew Richard foaf_name: Robinson, Matthew Richard foaf_surname: Robinson foaf_workInfoHomepage: http://www.librecat.org/personId=E5D42276-F5DA-11E9-8E24-6303E6697425 orcid: 0000-0001-8982-8813 - foaf_Person: foaf_givenName: Peter M. foaf_name: Visscher, Peter M. foaf_surname: Visscher bibo_doi: 10.1073/pnas.1621096114 bibo_issue: '32' bibo_volume: 114 dct_date: 2017^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/0027-8424 - http://id.crossref.org/issn/1091-6490 dct_language: eng dct_publisher: Proceedings of the National Academy of Sciences@ dct_title: Detection and quantification of inbreeding depression for complex traits from SNP data@ ...