Permutation testing in the presence of polygenic variation

Genetic Epidemiology
Mark Abney

Abstract

This article discusses problems with and solutions to performing valid permutation tests for quantitative trait loci in the presence of polygenic effects. Although permutation testing is a popular approach for determining statistical significance of a test statistic with an unknown distribution--for instance, the maximum of multiple correlated statistics or some omnibus test statistic for a gene, gene-set, or pathway--naive application of permutations may result in an invalid test. The risk of performing an invalid permutation test is particularly acute in complex trait mapping where polygenicity may combine with a structured population resulting from the presence of families, cryptic relatedness, admixture, or population stratification. I give both analytical derivations and a conceptual understanding of why typical permutation procedures fail and suggest an alternative permutation-based algorithm, MVNpermute, that succeeds. In particular, I examine the case where a linear mixed model is used to analyze a quantitative trait and show that both phenotype and genotype permutations may result in an invalid permutation test. I provide a formula that predicts the amount of inflation of the type 1 error rate depending on the degree o...Continue Reading

References

May 20, 1999·American Journal of Human Genetics·D B AllisonE R Martin
Mar 21, 2000·American Journal of Human Genetics·M AbneyC Ober
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Oct 9, 2001·American Journal of Human Genetics·D L NewmanN J Cox
Jan 5, 2002·Genetic Epidemiology·Silviu-Alin BacanuKathryn Roeder
Mar 24, 2005·European Journal of Human Genetics : EJHG·Catherine Bourgain, Emmanuelle Génin
Jul 20, 2011·Genetic Epidemiology·Saonli Basu, Wei Pan
Sep 3, 2011·American Journal of Human Genetics·Dan-Yu Lin, Zheng-Zheng Tang
Dec 14, 2011·Genetic Epidemiology·Rémi Kazma, Julia N Bailey
Jun 8, 2012·Genetic Epidemiology·Shurong FangShuanglin Zhang
Jul 24, 2012·American Journal of Human Genetics·Michael P EpsteinGlen A Satten
Aug 30, 2014·Genetic Epidemiology·Qunyuan ZhangMichael A Province
Dec 19, 2014·BMC Proceedings·Brian GrecoNathan L Tintle

❮ Previous
Next ❯

Citations

Feb 13, 2016·BMC Genetics·Stephanie A Santorico, Audrey E Hendricks
Mar 5, 2016·Human Molecular Genetics·Darren A CusanovichCarole Ober
Apr 4, 2016·Genome Biology·Jong Wha J JooEleazar Eskin
Jun 14, 2016·Cell·UNKNOWN 1001 Genomes Consortium. Electronic address: magnus.nordborg@gmi.oeaw.ac.at, UNKNOWN 1001 Genomes Consortium
Apr 4, 2017·Nucleic Acids Research·Shiquan SunXiang Zhou
Dec 3, 2016·Genetic Epidemiology·Sharon M LutzChristoph Lange
Jan 16, 2020·Nature Communications·Niraj ShahStig Uggerhøj Andersen
Dec 20, 2018·Evolution Letters·Petri Kemppainen, Arild Husby
Jan 7, 2020·American Journal of Human Genetics·Andy DahlNoah Zaitlen
Nov 6, 2018·G3 : Genes - Genomes - Genetics·Robert W Corty, William Valdar

❮ 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.