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Joint Modelling of Confounding Factors and Prominent Genetic Regulators Provides Increased Accuracy in Genetical Genomics Studies

Nicoló Fusi, Oliver Stegle, Neil D. Lawrence, Matthew Stephens
2012 PLoS Computational Biology  
In contrast to previous methods, PANAMA learns hidden factors jointly with the effect of prominent genetic regulators.  ...  Here, we report PANAMA (Probabilistic ANAlysis of genoMic dAta), a novel probabilistic model to account for confounding factors within an eQTL analysis.  ...  Acknowledgments The authors would like to thank Leonid Kruglyak, Erin Smith and Rachel Brem for access to gene expression and genotype data as well as permission to include the primary data alongside with  ... 
doi:10.1371/journal.pcbi.1002330 pmid:22241974 pmcid:PMC3252274 fatcat:ozz2kxje2jbzjff5d63x7k2zgq

Accurate modeling of confounding variation in eQTL studies leads to a great increase in power to detect trans-regulatory effects

Nicolo Fusi, Oliver Stegle, Neil Lawrence
2011 Nature Precedings  
In contrast to previous methods, PANAMA learns hidden factors jointly with the effect of prominent genetic regulators.  ...  Here, we report PANAMA (Probabilistic ANAlysis of genoMic dAta), a novel probabilistic model to account for confounding factors within an eQTL analysis.  ...  Acknowledgments This research was supported by the FP7 PASCAL II Network of Excellence. NF was supported by PhD scolarships from the University of Sheffield and the University of Manchester.  ... 
doi:10.1038/npre.2011.5995.1 fatcat:dvekebbgi5btnbt7ixu5es2aha

On Using Local Ancestry to Characterize the Genetic Architecture of Human Traits: Genetic Regulation of Gene Expression in Multiethnic or Admixed Populations

Yizhen Zhong, Minoli A. Perera, Eric R. Gamazon
2019 American Journal of Human Genetics  
By using simulations of diverse genetic architectures and degrees of confounding, we show improved accuracy in estimating heritability when accounting for local ancestry similarity.  ...  We provide a computationally efficient approach to local ancestry analysis in eQTL mapping while increasing control of type I and type II error over traditional approaches.  ...  We thank Tanima De, Zhou Zhang, Yiben The American Journal of Human Genetics 104, 1097-1115, June 6, 2019 1113 Yang, and Jun Xiong for helpful discussion.  ... 
doi:10.1016/j.ajhg.2019.04.009 pmid:31104770 pmcid:PMC6562007 fatcat:7scf3lgatrhtdcu75recwjeoee

48th European Mathematical Genetics Meeting (EMGM) 2020

Zoltan Kutalik
2020 Human Heredity  
We considered various combinations of factors, including varying effect sizes, variant allele frequencies, numbers of disease SNPs, varying sample sizes and the degree of genetic overlap between the phenotypes  ...  of European ancestry based on the 1000 Genomes project.  ...  in sequencing accuracy across the genome, and the efficacy of quality control measures.  ... 
doi:10.1159/000507248 pmid:32268327 fatcat:3aneluafpnes3a2ayzn53uffca

Detecting regulatory gene–environment interactions with unmeasured environmental factors

Nicoló Fusi, Christoph Lippert, Karsten Borgwardt, Neil D. Lawrence, Oliver Stegle
2013 Computer applications in the biosciences : CABIOS  
To fully understand the genetic regulation of gene expression variability, it is important to study the effect of genotype in the context of external factors such as alternative environmental conditions  ...  Motivation: Genomic studies have revealed a substantial heritable component of the transcriptional state of the cell.  ...  Funding: FP7 PASCAL II Network of Excellence; University of Sheffield doctoral training award (to N.F.); Volkswagen Foundation and a Marie Curie FP7 grant (to O.S.).  ... 
doi:10.1093/bioinformatics/btt148 pmid:23559640 fatcat:n24ytrgecnhmvjthheers2q3pa

On Using Local Ancestry to Characterize the Genetic Architecture of Human Phenotypes: Genetic Regulation of Gene Expression in Multiethnic or Admixed Populations as a Model [article]

Yizhen Zhong, Minoli A Perera, Eric R Gamazon
2018 bioRxiv   pre-print
Using simulations of diverse genetic architectures to estimate trait heritability and the level of confounding, we show improved accuracy given individual-level data and evaluate a summary statistics based  ...  Furthermore, we provide a computationally efficient approach to local ancestry analysis in eQTL mapping while increasing control of type I and type II error over traditional approaches.  ...  Taken together, 406 these results substantially extend existing approaches and provide a framework for future large-scale studies of genetic 407 regulation of gene expression in multiethnic or admixed  ... 
doi:10.1101/483107 fatcat:ip4sez2zdrhgtnfqtmpfyfdwbq

Adoption and Optimization of Genomic Selection To Sustain Breeding for Apricot Fruit Quality

Mariem Nsibi, Barbara Gouble, Sylvie Bureau, Timothée Flutre, Christopher Sauvage, Jean-Marc Audergon, Jean-Luc Regnard
2020 G3: Genes, Genomes, Genetics  
Useful insights were provided on the genetic architecture of apricot fruit quality whose integration in prediction models improved their performance, notably for traits governed by major QTLs.  ...  Genomic selection (GS) is a breeding approach which exploits genome-wide information and whose unprecedented success has shaped several animal and plant breeding schemes through delivering their genetic  ...  Therefore, higher degree of IBD sharing between full-sibs is likely to provide accurate estimation of genetic variation for quantitative traits exempt from confounding nongenetic factors in comparison  ... 
doi:10.1534/g3.120.401452 pmid:33067307 pmcid:PMC7718743 fatcat:ov2ws3xkzzguhhttfo7ikak3sy

Pathogenetic Overview of Psoriatic Disease

M. HAROON, O. FITZGERALD
2012 Journal of Rheumatology Supplement  
Similarly, there are important new genetic observations focusing on the HLA region, and genome-wide association that confirms the genetic heterogeneity of patients with psoriasis and patients with PsA.  ...  Apart from peripheral joint involvement, the musculoskeletal lesions in PsA include enthesitis and involvement of the distal interphalangeal joint (frequently associated with nail involvement, dactylitis  ...  There are many factors that can confound identifying susceptibility genes in PsA.  ... 
doi:10.3899/jrheum.120232 pmid:22751581 fatcat:dftfaquiofhujmedc3x6tsngge

Synergistic Association of Genetic Variants with Environmental Risk Factors in Susceptibility to Essential Hypertension

Ana Célia Sousa, Maria I. Mendonça, Andreia Pereira, Sara Gouveia, Ana I. Freitas, Graça Guerra, Mariana Rodrigues, Eva Henriques, Sónia Freitas, Sofia Borges, Décio Pereira, António Brehm (+1 others)
2017 Genetic Testing and Molecular Biomarkers  
This study was designed to identify the interaction model between genetic variants and environmental risk factors that most highly potentiates EH development.  ...  Traditional risk factors, biochemical and genetic parameters, including the genotypic discrimination of 14 genetic variants previously associated with EH, were investigated.  ...  Acknowledgment This study was supported by the European Regional Development Fund's Operational Program for the Enhancement of Economic Potential and Territorial Cohesion for the Autonomous Region of Madeira  ... 
doi:10.1089/gtmb.2017.0048 pmid:28872890 fatcat:xaqwcnvqkff6fbgtg5up6cdote

Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus

Xu-jie Zhou, Xiao-lan Lu, Swapan K. Nath, Ji-cheng Lv, Sai-nan Zhu, Hai-zhen Yang, Lian-xiang Qin, Ming-hui Zhao, Yin Su, Nan Shen, Zhan-guo Li, Hong Zhang
2011 Arthritis & Rheumatism  
Recent genome-wide association studies (GWAS) in SLE have produced renewed interest in B cell/T cell responses and the NF-κB signaling pathway.  ...  Objective-Although the number of convincingly established genetic associations with systemic lupus erythematosus (SLE) has increased sharply over the last few years, refinement of these associations is  ...  In the Chinese population, the regression models were adjusted for the potential confounders, including age and sex.  ... 
doi:10.1002/art.33318 pmid:21905002 pmcid:PMC3994469 fatcat:ols2gilf7fftjg3desoqernv3u

Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity: Recent Advances and Future Perspectives

Konstantin G. Arbeev, Igor Akushevich, Alexander M. Kulminski, Svetlana V. Ukraintseva, Anatoliy I. Yashin
2014 Advances in Geriatrics  
using Medicare claims data; (2) methodological advances in genetic and genomic biodemography and applications to research on genetic determinants of longevity and health; and (3) biodemographic models  ...  for joint analyses of time-to-event data and longitudinal measurements of biomarkers collected in longitudinal studies on aging.  ...  Acknowledgments Research reported in this publication was partly supported by the National Institute on Aging of the National Institutes of Health under Awards nos. R01AG046860 and R21AG045245.  ... 
doi:10.1155/2014/957073 pmid:25590047 pmcid:PMC4290867 fatcat:26oj35e6prcuxnv5obijbpzae4

Gene–environment-wide association studies: emerging approaches

Duncan Thomas
2010 Nature reviews genetics  
Acknowledgements S u p p o r t e d i n p a r t b y g r a n t s 5 P 3 0 E S 0 070 4 3 , 1U01 ES15090 and 1R01 ES016813 from the US National Institute of Environmental Health Sciences.  ...  Gilliland and R. Haile for many helpful suggestions.  ...  Confounder A spurious association between a risk factor (a gene, exposure or interaction) and disease induced by the joint associations of some other variable with the risk factor and the disease that  ... 
doi:10.1038/nrg2764 pmid:20212493 pmcid:PMC2891422 fatcat:hsbxlwi5dzfttidv2kbvxtzmoi

44th European Mathematical Genetics Meeting (EMGM) 2016. Newcastle upon Tyne, UK, May 11-12, 2016: Abstracts

2015 Human Heredity  
Complex diseases are supposed to be driven by multiple interactions between genetic factors and environmental exposures.  ...  Then, in a second part, the method is used in a complex simulation scenario attempting to mimic the GxE interaction between a dominant genetic factor and a treatment with appetite suppressant effect.  ...  assigned to genes based on the locations in build 37.3 of the human reference genome.  ... 
doi:10.1159/000445228 pmid:27111916 fatcat:553k64equ5f7lkbhpwun7nbgkm

The landscape of microbial phenotypic traits and associated genes

Maria Brbić, Matija Piškorec, Vedrana Vidulin, Anita Kriško, Tomislav Šmuc, Fran Supek
2016 Nucleic Acids Research  
Moreover, the Pro-Traits pipeline assigns phenotypes by drawing extensively on comparative genomics, capturing patterns in gene repertoires, codon usage biases, proteome composition and co-occurrence in  ...  A global analysis of trait interrelatedness outlined clusters in the microbial phenotype network, suggesting common genetic underpinnings.  ...  There is a known confounding effect of genome size with the other genetic determinants of spore-forming ability (52) .  ... 
doi:10.1093/nar/gkw964 pmid:27915291 pmcid:PMC5137458 fatcat:xnrilp536japlcojdc3xysfl3m

OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals

Jamie Soul, Matthew J Barter, Christopher B Little, David A Young
2020 Annals of the Rheumatic Diseases  
and online resource for understanding gene regulation of animal model OA pathogenesis.  ...  Several discrepancies between different studies were identified, providing lessons on interpretation of these data.  ...  Acknowledgements The authors thank Louise Reynard, Newcastle University for helpful discussions regarding the database and the manuscript.  ... 
doi:10.1136/annrheumdis-2020-218344 pmid:33077471 pmcid:PMC7892386 fatcat:ijvatzbq7jddnkkroz4heen2vm
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