Utilising family-based designs for detecting rare variant disease associations.

Preston, MD; Dudbridge, F; (2013) Utilising family-based designs for detecting rare variant disease associations. Annals of human genetics, 78 (2). pp. 129-40. ISSN 0003-4800 DOI: https://doi.org/10.1111/ahg.12051

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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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Centre for Statistical Methodology
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PubMed ID: 24571231
Web of Science ID: 331649500006
URI: http://researchonline.lshtm.ac.uk/id/eprint/1591972


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