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Utilising Family‐Based Designs for Detecting Rare Variant Disease Associations
Author(s) -
Preston Mark D.,
Dudbridge Frank
Publication year - 2014
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/ahg.12051
Subject(s) - pedigree chart , genotyping , statistical power , causality (physics) , genetics , biology , computer science , computational biology , statistics , mathematics , genotype , gene , physics , quantum mechanics
Summary Rare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family‐based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case–control rare variant tests. However, we show that transmission‐ (or within‐family‐) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo‐case–control design allows a greater range of statistical tests to be applied to family data.