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Ignoring Distant Genealogic Loops Leads to False‐positives in Homozygosity Mapping
Author(s) -
Liu F.,
Elefante S.,
Van Duijn C. M.,
Aulchenko Y. S.
Publication year - 2006
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2006.00279.x
Subject(s) - inbreeding , false positive paradox , linkage (software) , consanguinity , genetics , biology , genetic linkage , runs of homozygosity , evolutionary biology , statistics , population , mathematics , medicine , gene , genotype , environmental health , single nucleotide polymorphism
Summary 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.