Journal article

Quantification of Inbreeding Due to Distant Ancestors and Its Detection Using Dense Single Nucleotide Polymorphism Data

Matthew C Keller, Peter M Visscher, Michael E Goddard

Genetics: a periodical record of investigations bearing on heredity and variation | GENETICS SOCIETY AMERICA | Published : 2011

Abstract

Inbreeding depression, which refers to reduced fitness among offspring of related parents, has traditionally been studied using pedigrees. In practice, pedigree information is difficult to obtain, potentially unreliable, and rarely assessed for inbreeding arising from common ancestors who lived more than a few generations ago. Recently, there has been excitement about using SNP data to estimate inbreeding (F) arising from distant common ancestors in apparently "outbred" populations. Statistical power to detect inbreeding depression using SNP data depends on the actual variation in inbreeding in a population, the accuracy of detecting that with marker data, the effect size, and the sample siz..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Mental Health


Awarded by Medical Research Council


Awarded by Australian Research Council


Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH


Funding Acknowledgements

The authors thank Matthew C. Jones for his statistical advice, Daniel P. Howrigan for help in conducting and finding optimal thresholds for the simulation, and Tony Sun for modifying the Fregene program. The data sets used for the analyses described in this article were obtained from the database of genotype and phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession nos. phs000021.v3.p2 and phs000167.v1.p1. Samples and associated phenotype data for the genome-wide association of schizophrenia study were provided by the Molecular Genetics of Schizophrenia Collaboration [Principal Investigator: P. V. Gejman, Evanston Northwestern Healthcare and Northwestern University, Evanston, IL]. M.C.K.,P.M.V., and M.E.G. conceived and designed this study; M.C.K. conducted analyses; and M.C.K., P.M.V., and M.E.G. wrote the article. The authors declare that no competing interests exist. This study was supported by a grant from the National Institutes of Health and the National Institutes of Mental Health (MH085812) (to M.C.K.). P.M.V. and M.E.G. acknowledge funding from the Australian National Health and Medical Research Council (grants 613672 and 613601) and the Australian Research Council (grants DP0770096 and DP1093900). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.