Meta-analysis of gene-level tests for rare variant association

The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharin...

Full description

Saved in:
Bibliographic Details
Published inNature genetics Vol. 46; no. 2; pp. 200 - 204
Main Authors Liu, Dajiang J, Peloso, Gina M, Zhan, Xiaowei, Holmen, Oddgeir L, Zawistowski, Matthew, Feng, Shuang, Nikpay, Majid, Auer, Paul L, Goel, Anuj, Zhang, He, Peters, Ulrike, Farrall, Martin, Orho-Melander, Marju, Kooperberg, Charles, McPherson, Ruth, Watkins, Hugh, Willer, Cristen J, Hveem, Kristian, Melander, Olle, Kathiresan, Sekar, Abecasis, Gonçalo R
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.02.2014
Subjects
Blood lipids
Cardiac and Cardiovascular Systems
Cholesterol
Clinical Medicine
Data Interpretation, Statistical
Endocrinology and Diabetes
Endokrinologi och diabetes
Exome - genetics
Genes
Genetic aspects
Genetic Association Studies - methods
Genetic Variation
Genetics, Population
Genomes
Genotype
Grants
Heart
Humans
Kardiologi
Klinisk medicin
Lipids - blood
Lipids - genetics
Medical and Health Sciences
Medical research
Medicin och hälsovetenskap
Meta-analysis
Meta-Analysis as Topic
Methods
Models, Genetic
Monte Carlo Method
Physiological aspects
Population
Research Design
Software
Studies
United States
Online AccessGet full text

Cover

More Information
Summary:The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally and should be considered joint first authors.
These authors jointly directed the study.
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.2852