title: Family-based designs for genome-wide association studies.
abstract: Association mapping has successfully identified common SNPs associated with many diseases. However, the inability of this class of variation to account for most of the supposed heritability has led to a renewed interest in methods - primarily linkage analysis - to detect rare variants. Family designs allow for control of population stratification, investigations of questions such as parent-of-origin effects and other applications that are imperfectly or not readily addressed in case-control association studies. This article guides readers through the interface between linkage and association analysis, reviews the new methodologies and provides useful guidelines for applications. Just as effective SNP-genotyping tools helped to realize the potential of association studies, next-generation sequencing tools will benefit genetic studies by improving the power of family-based approaches.
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 4A Datun Road, Chaoyang District, Beijing 100101, China. ottjurg@psych.ac.cn
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
mesh_terms: D003625:Data Collection / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D015340:Epidemiologic Research Design; D005190:Family; D008040:Genetic Linkage; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D010375:Pedigree; D012985:Software Design