Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Distant consanguineous loops are often unknown or ignored during homozygosity mapping analysis. This may potentially lead to an increased rate of false-positive linkage results. We show that failure to take into account the distant loops may seriously underestimate the degree of consanguinity, especially for people from genetically isolated populations; in 6 Alzheimer's disease (AD) patients the distant loops accounted for 57.7 % of inbreeding on average. Theoretical evaluation showed that ignoring distant loops, which account for 18-75% of inbreeding, inflates the frequency of false positive conclusions substantially in 2-point linkage analysis, up to several hundred times. In multipoint linkage analysis of the 6 AD patients a chromosome-wide "empirical" significance of 5% corresponded to a true false positive rate of 11.1%. We show that converting multiple loops to a hypothetical loop capturing all inbreeding may be a convenient solution to avoid false positive results. When extended genealogic data are not available a hypothetical loop may still be constructed based on genomic data.

Original publication

DOI

10.1111/j.1469-1809.2006.00279.x

Type

Journal article

Journal

Annals of human genetics

Publication Date

11/2006

Volume

70

Pages

965 - 970

Addresses

Department of Epidemiology & Biostatistics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.

Keywords

Humans, Alzheimer Disease, Chromosome Mapping, Pedigree, Consanguinity, Homozygote, Lod Score, Genealogy and Heraldry, Female, Male, Genetic Linkage