Back to Search
Start Over
Association score testing for rare variants and binary traits in family data with shared controls
- Publication Year :
- 2017
- Publisher :
- Oxford University Press, 2017.
-
Abstract
- Genome-wide association studies have been an important approach used to localize trait loci, with primary focus on common variants. The multiple rare variant-common disease hypothesis may explain the missing heritability remaining after accounting for identified common variants. Advances of sequencing technologies with their decreasing costs, coupled with methodological advances in the context of association studies in large samples, now make the study of rare variants at a genome-wide scale feasible. The resurgence of family-based association designs because of their advantage in studying rare variants has also stimulated more methods development, mainly based on linear mixed models (LMMs). Other tests such as score tests can have advantages over the LMMs, but to date have mainly been proposed for single-marker association tests. In this article, we extend several score tests (χcorrected2, WQLS, and SKAT) to the multiple variant association framework. We evaluate and compare their statistical performances relative with the LMM. Moreover, we show that three tests can be cast as the difference between marker allele frequencies (AFs) estimated in each of the group of affected and unaffected subjects. We show that these tests are flexible, as they can be based on related, unrelated or both related and unrelated subjects. They also make feasible an increasingly common design that only sequences a subset of affected subjects (related or unrelated) and uses for comparison publicly available AFs estimated in a group of healthy subjects. Finally, we show the great impact of linkage disequilibrium on the performance of all these tests.
- Subjects :
- Paper
Male
Linkage disequilibrium
0206 medical engineering
Quantitative Trait Loci
Context (language use)
02 engineering and technology
Computational biology
Biology
Bioinformatics
Generalized linear mixed model
Linkage Disequilibrium
03 medical and health sciences
Gene Frequency
Missing heritability problem
Humans
Computer Simulation
Association (psychology)
Molecular Biology
Allele frequency
030304 developmental biology
Genetic association
0303 health sciences
Models, Genetic
Computational Biology
Genetic Variation
High-Throughput Nucleotide Sequencing
Sequence Analysis, DNA
Pedigree
Case-Control Studies
Trait
Linear Models
Feasibility Studies
Female
020602 bioinformatics
Information Systems
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....148e658bcce4f3b970c3518580c63a14