Proper conditional analysis in the presence of missing data: Application to large scale meta-analysis of tobacco use phenotypes.

PLoS Genetics
Yu JiangDajiang J Liu

Abstract

Meta-analysis of genetic association studies increases sample size and the power for mapping complex traits. Existing methods are mostly developed for datasets without missing values, i.e. the summary association statistics are measured for all variants in contributing studies. In practice, genotype imputation is not always effective. This may be the case when targeted genotyping/sequencing assays are used or when the un-typed genetic variant is rare. Therefore, contributed summary statistics often contain missing values. Existing methods for imputing missing summary association statistics and using imputed values in meta-analysis, approximate conditional analysis, or simple strategies such as complete case analysis all have theoretical limitations. Applying these approaches can bias genetic effect estimates and lead to seriously inflated type-I or type-II errors in conditional analysis, which is a critical tool for identifying independently associated variants. To address this challenge and complement imputation methods, we developed a method to combine summary statistics across participating studies and consistently estimate joint effects, even when the contributed summary statistics contain large amounts of missing values. B...Continue Reading

References

Sep 7, 2005·Archives of General Psychiatry·Michael C StallingsThomas J Crowley
Mar 24, 2006·The New England Journal of Medicine·Jonathan C CohenHelen H Hobbs
Aug 29, 2006·PLoS Genetics·Giuseppe PiliaDavid Schlessinger
Apr 9, 2008·American Journal of Human Genetics·Claudio VerzilliAroon D Hingorani
May 5, 2009·American Journal of Human Genetics·Paul J NewcombeJohn C Whittaker
Apr 27, 2010·Nature Genetics·Thorgeir E ThorgeirssonKari Stefansson
Feb 1, 2013·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Michael B MillerMatt McGue
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
Oct 8, 2013·Biological Psychiatry·Scott I VriezeMatt McGue
Dec 10, 2013·Nucleic Acids Research·Danielle WelterHelen Parkinson
Dec 18, 2013·Nature Genetics·Dajiang J LiuGonçalo R Abecasis
May 7, 2014·Genetic Epidemiology·Zheng-Zheng Tang, Dan-Yu Lin
Jun 5, 2014·Bioinformatics·Shuang FengGonçalo R Abecasis
Jun 19, 2014·The New England Journal of Medicine·Jacy CrosbySekar Kathiresan
Feb 3, 2015·Nature Genetics·Brendan K Bulik-SullivanBenjamin M Neale
Jun 23, 2015·American Journal of Human Genetics·Zheng-Zheng Tang, Dan-Yu Lin
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Jan 7, 2016·American Journal of Respiratory and Critical Care Medicine·Dandi QiaoUNKNOWN COPDGene Investigators
Aug 23, 2016·Nature Genetics·Shane McCarthyUNKNOWN Haplotype Reference Consortium
Aug 30, 2016·Nature Genetics·Sayantan DasChristian Fuchsberger
Apr 26, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Xianyong YinKirk C Wilhelmsen

❮ Previous
Next ❯

Citations

Mar 9, 2019·Current Protocols in Human Genetics·J Dylan WeissenkampenDajiang J Liu
Jun 27, 2019·Annals of Neurology·Susanna C LarssonKarl Michaëlsson
Apr 1, 2021·Nature Communications·Daniel McGuireDajiang J Liu
Sep 4, 2021·Scientific Reports·Rowland W PettitChristopher I Amos
Dec 21, 2021·Emerging Topics in Life Sciences·Rowland W PettitChristopher I Amos

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping

Software Mentioned

RVTESTS
abolic S yndrome I n M en ( METSIM )
RAREMETAL
rareGWAMA
COJO
COPDGene
FINEMAP
impG
PCBS
MET

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.