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Design considerations for genetic linkage and association studies

Lookup NU author(s): Dr Jérémie Nsengimana


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© 2017, Springer Science+Business Media LLC.This chapter describes the main issues that genetic epidemiologists usually consider in the design of linkage and association studies. For linkage, we briefly consider the situation of rare highly penetrant alleles showing a disease pattern consistent with Mendelian inheritance investigated through parametric methods in large pedigrees, or with autozygosity mapping in inbred families, and we then turn our focus to the most common design, the affected sibling pair design that is of more relevance for common, complex diseases. Power and sample size calculations are provided as a function of the strength of the genetic effect being investigated. We also discuss the impact of other determinants of statistical power such as disease heterogeneity, pedigree and genotyping errors and the effect of the type and density of genetic markers. For association studies, we consider the popular case–control design for dichotomous phenotypes and we provide power and sample size calculations for one-stage and multistage designs. For candidate genes, guidelines are given on the prioritization of genetic variants, and for genome-wide association studies (GWAS) the issue of choosing an appropriate SNP array is discussed. A warning is issued regarding the danger of designing an underpowered replication study following an initial GWAS. The risk of finding spurious association due to population stratification, cryptic relatedness, and differential bias is underlined.

Publication metadata

Author(s): Nsengimana J, Bishop DT

Publication type: Book Chapter

Publication status: Published

Book Title: Statistical Human Genetics : Methods and Protocols

Year: 2017

Volume: 1666

Pages: 257-281

Print publication date: 01/10/2017

Online publication date: 05/10/2017

Acceptance date: 02/04/2016

Series Title: Methods in Molecular Biology

Publisher: Humana Press Inc.

Place Published: New York


DOI: 10.1007/978-1-4939-7274-6_13

PubMed id: 28980250

Library holdings: Search Newcastle University Library for this item

ISBN: 9781493972739