A nonparametric test to detect quantitative trait loci where the phenotypic distribution differs by genotypes

Genetic Epidemiology
Hugues AschardPeter Kraft

Abstract

Searching for genetic variants involved in gene-gene and gene-environment interactions in large-scale data raises multiple methodological issues. Many existing methods have focused on the problem of dimensionality, trying to explore the largest number of combinations between risk factors while considering simple interaction models. Despite evidence demonstrating the efficacy of these methods in simulated data, their application in real data has been unsuccessful so far. The classical test of a linear marginal genetic effect has been widely used for agnostic genome-wide association studies, with the underlying idea that most variants involved in interactions might display marginal effect on the phenotypic mean. Although this approach may allow for the identification of genetic variants involved in interactions in many scenarios, the linear marginal effects of some causal alleles on the phenotypic mean might not be always detectable at genome-wide significance level. We introduce in this study a general association test for quantitative trait loci that compare the distributions of phenotypic values by genotypic classes as opposed to most standard tests that compare phenotypic means by genotypic classes. Using simulations we show ...Continue Reading

References

Oct 1, 1996·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·J W ByngM J Yaffe
Feb 3, 2004·Behavior Genetics·Maurice ZeegersPak Sham
Feb 18, 2005·Nature Reviews. Genetics·Joel N Hirschhorn, Mark J Daly
Mar 29, 2005·Nature Genetics·Jonathan MarchiniLon R Cardon
Apr 2, 2005·Nature Reviews. Genetics·David J Hunter
May 3, 2005·Nature Reviews. Cancer·Graham A Colditz, Susan E Hankinson
May 26, 2006·Applied Bioinformatics·Brett A McKinneyJason H Moore
Sep 28, 2006·PLoS Genetics·David M EvansLon R Cardon
Feb 7, 2007·Human Heredity·Peter KraftW James Gauderman
Aug 28, 2007·Nature Genetics·Yu Zhang, Jun S Liu
Jan 18, 2008·Genetic Epidemiology·Charles Kooperberg, Michael Leblanc
Nov 22, 2008·American Journal of Epidemiology·Cassandra E MurcrayW James Gauderman
May 13, 2009·Nature Reviews. Genetics·Heather J Cordell
Jul 9, 2009·Nature Reviews. Genetics·Trudy F C MackayJulien F Ayroles
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Mar 10, 2010·Nature Reviews. Genetics·Duncan Thomas
May 19, 2010·Nature Reviews. Genetics·Evan E EichlerJoseph H Nadeau
Oct 28, 2010·Annals of Human Genetics·Matthew Reimherr, Dan L Nicolae
Jul 20, 2011·Genetic Epidemiology·Serkalem Demissie, L Adrienne Cupples
Dec 17, 2011·Science·David N ReshefPardis C Sabeti
Dec 27, 2011·American Journal of Epidemiology·Bhramar MukherjeeNilanjan Chatterjee

Citations

Feb 1, 2014·Genetic Epidemiology·Ying CaoTaylor J Maxwell
Sep 18, 2014·Annals of Human Genetics·Xin WangJung-Ying Tzeng
Jul 4, 2015·American Journal of Human Genetics·David SoaveLei Sun
Apr 22, 2014·American Journal of Human Genetics·Hugues AschardPeter Kraft
Jul 9, 2016·Genetic Epidemiology·Hugues Aschard
Oct 6, 2017·American Journal of Epidemiology·W James GaudermanNilanjan Chatterjee
Oct 6, 2017·American Journal of Epidemiology·Kimberly McAllisterJohn S Witte
Apr 5, 2018·PloS One·Dalton ConleyMark L Siegal
Dec 22, 2019·Biometrics·Rui DuanYong Chen
Nov 20, 2016·Biometrics·Chuan HongYong Chen
Mar 17, 2017·PloS One·Peter J CastaldiHugues Aschard

Related Concepts

In Silico
Mammography
Computer Programs and Programming
Log-Linear Models
Quantitative Trait, Heritable
Quantitative Trait Loci
Genome-Wide Association Study
Alleles
Genes
Genome

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.

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.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.