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

Nature Genetics
Dajiang J LiuGonçalo R Abecasis

Abstract

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.

References

Dec 4, 2001·Nature Genetics·Gonçalo R AbecasisLon R Cardon
May 5, 2007·Science·Ruth McPhersonJonathan C Cohen
Mar 11, 2008·Nature Biotechnology·Nayanah Siva
Mar 21, 2008·The New England Journal of Medicine·Sekar KathiresanMarju Orho-Melander
Sep 2, 2008·Nature·John NovembreCarlos D Bustamante
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Gregory V KryukovShamil R Sunyaev
Feb 14, 2009·PLoS Genetics·Bo Eskerod Madsen, Sharon R Browning
Oct 8, 2009·Genetic Epidemiology·Andrew P Morris, Eleftheria Zeggini
Dec 25, 2009·The New England Journal of Medicine·Robert ClarkeUNKNOWN PROCARDIS Consortium
May 18, 2010·American Journal of Human Genetics·Alkes L PriceShamil R Sunyaev
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Dec 7, 2010·American Journal of Human Genetics·Dajiang J Liu, Suzanne M Leal
Mar 17, 2011·PLoS Genetics·Benjamin M NealeMark J Daly
Jun 10, 2011·Bioinformatics·Petr DanecekUNKNOWN 1000 Genomes Project Analysis Group
Jul 9, 2011·American Journal of Human Genetics·Michael C WuXihong Lin
Sep 3, 2011·American Journal of Human Genetics·Dan-Yu Lin, Zheng-Zheng Tang
May 19, 2012·Science·Jacob A TennessenUNKNOWN NHLBI Exome Sequencing Project
May 30, 2012·Nature Genetics·Adam KiezunShamil R Sunyaev
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Aug 11, 2012·International Journal of Epidemiology·S KrokstadJ Holmen
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
May 24, 2013·Bioinformatics·Zheng-Zheng Tang, Dan-Yu Lin
Jun 19, 2013·American Journal of Human Genetics·Seunggeun LeeXihong Lin
Jul 31, 2013·American Journal of Human Genetics·Yi-Juan HuDan-Yu Lin

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Citations

Jun 19, 2013·American Journal of Human Genetics·Seunggeun LeeXihong Lin
Jun 23, 2015·Nature Genetics·Hannes HelgasonKari Stefansson
Feb 25, 2015·Genome Medicine·Paul L Auer, Guillaume Lettre
May 12, 2015·Nature Genetics·Ida SurakkaUNKNOWN ENGAGE Consortium
Apr 24, 2015·Frontiers in Genetics·Qunyuan Zhang
Sep 26, 2014·Bioinformatics·Tatsiana VaitsiakhovichTim Becker
Feb 13, 2016·BMC Genetics·Stephanie A Santorico, Audrey E Hendricks
Aug 16, 2016·Human Molecular Genetics·Xiangfeng LuDongfeng Gu
Sep 1, 2016·European Journal of Human Genetics : EJHG·Tom G RichardsonTom R Gaunt
Aug 26, 2016·Human Molecular Genetics·Tom G RichardsonTom R Gaunt
Nov 15, 2016·Nature Reviews. Genetics·Bogdan Pasaniuc, Alkes L Price
Sep 23, 2016·Journal of Dental Research·E KasbohmA Teumer
Nov 13, 2015·Scientific Reports·Berta Luzón-ToroSalud Borrego
Jun 28, 2016·American Journal of Human Genetics·Nathalie ChamiGuillaume Lettre
Jun 28, 2016·American Journal of Human Genetics·John D EicherAndrew D Johnson
Oct 31, 2017·Nature Genetics·Dajiang J LiuSekar Kathiresan
Mar 12, 2016·Science·Paolo ZanoniUNKNOWN Global Lipids Genetics Consortium
Sep 7, 2018·Genetic Epidemiology·Li-Chu Chien, Yen-Feng Chiu
Nov 17, 2016·European Journal of Human Genetics : EJHG·James P CookAndrew P Morris
Mar 9, 2019·Current Protocols in Human Genetics·J Dylan WeissenkampenDajiang J Liu
May 26, 2016·Human Genetics·Jack A KosmickiBenjamin M Neale
May 31, 2019·PloS One·Matt J NevilleFredrik Karpe
May 10, 2019·Acta Neurologica Scandinavica·Berta AlmogueraUNKNOWN eMERGE Epilepsy Research Group

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Methods Mentioned

BETA
exome
genotyping

Software Mentioned

PLINK
Merlin
ms

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