Estimating the posterior probability that genome-wide association findings are true or false.

Bioinformatics
József BukszárEdwin J C G van den Oord

Abstract

A limitation of current methods used to declare significance in genome-wide association studies (GWAS) is that they do not provide clear information about the probability that GWAS findings are true of false. This lack of information increases the chance of false discoveries and may result in real effects being missed. We propose a method to estimate the posterior probability that a marker has (no) effect given its test statistic value, also called the local false discovery rate (FDR), in the GWAS. A critical step involves the estimation the parameters of the distribution of the true alternative tests. For this, we derived and implemented the real maximum likelihood function, which turned out to provide us with significantly more accurate estimates than the widely used mixture model likelihood. Actual GWAS data are used to illustrate properties of the posterior probability estimates empirically. In addition to evaluating individual markers, a variety of applications are conceivable. For instance, posterior probability estimates can be used to control the FDR more precisely than Benjamini-Hochberg procedure. The codes are freely downloadable from the web site http://www.people.vcu.edu/~jbukszar.

References

Jun 1, 1992·Journal of Personality·T A Widiger, T J Trull
Apr 1, 1980·Journal of Personality and Social Psychology·P T Costa, R R McCrae
Oct 11, 2001·American Journal of Human Genetics·H H GöringJ Blangero
Oct 16, 2001·Nature Genetics·J P IoannidisD G Contopoulos-Ioannidis
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Oct 14, 2004·Bioinformatics·Cyril DalmassoThierry Moreau
Jul 16, 2005·Genetics·Dmitri V Zaykin, Lev A Zhivotovsky
Dec 22, 2005·Bioinformatics·Alexander PlonerYudi Pawitan
Aug 2, 2006·Current Psychiatry Reports·Mina Brandes, O Joseph Bienvenu
Oct 20, 2006·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Stefanie Scheid, Rainer Spang
Jul 3, 2007·BMC Bioinformatics·Cyril DalmassoPhilippe Broët
Feb 7, 2008·American Journal of Human Genetics·D Y LinB E Huang
Sep 3, 2008·Archives of General Psychiatry·Edwin J C G van den OordDan Rujescu

❮ Previous
Next ❯

Citations

Mar 3, 2010·Molecular Psychiatry·D E AdkinsE J C G van den Oord
Nov 26, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joseph L McClayEdwin J C G van den Oord
Oct 6, 2010·The Pharmacogenomics Journal·K AbergE J C G van den Oord
Apr 5, 2013·Metabolomics : Official Journal of the Metabolomic Society·Joseph L McClayEdwin J C G van den Oord
May 25, 2013·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Ye YangDavid R Bickel
Nov 27, 2018·PloS One·Farnoosh Abbas-AghababazadehDavid R Bickel
Apr 13, 2021·Medicine and Science in Sports and Exercise·J Timothy LightfootMonica J Hubal

❮ Previous
Next ❯

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.

Related Papers

The New England Journal of Medicine
Jeffrey A LiebermanClinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators
The British Journal of Psychiatry : the Journal of Mental Science
T R Barnes
Acta Psychiatrica Scandinavica
D J MüllerM Rietschel
© 2022 Meta ULC. All rights reserved