ArticleBMC genomics2014
Systematic permutation testing in GWAS pathway analyses: identification of genetic networks in dilated cardiomyopathy and ulcerative colitis.
Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
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- Statistical properties of functional connectivity MRI enrichment analysis in school-age autism research.Developmental cognitive neuroscience · 2025Article
- SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.NPJ genomic medicine · 2023Article
- Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure.Journal of cellular and molecular medicine · 2023Article
- Whole-Brain Resting-State Functional Connectivity Patterns Associated With Pediatric Anxiety and Involuntary Attention Capture.Biological psychiatry global open science · 2021Article
- Interactive relations between maternal prenatal stress, fetal brain connectivity, and gestational age at delivery.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Genetic Analysis of Functional Rare Germline Variants across Nine Cancer Types from an Electronic Health Record Linked Biobank.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- Associations of observed preschool performance monitoring with brain functional connectivity in adolescence.Cortex; a journal devoted to the study of the nervous system and behavior · 2021Article
- Identifying reproducible individual differences in childhood functional brain networks: An ABCD study.Developmental cognitive neuroscience · 2019Article
- Prenatal lead exposure impacts cross-hemispheric and long-range connectivity in the human fetal brain.NeuroImage · 2019Article
- Sex differences in functional connectivity during fetal brain development.Developmental cognitive neuroscience · 2019Article
- Investigation of multi-trait associations using pathway-based analysis of GWAS summary statistics.BMC genomics · 2019Article
- A Pathway Analysis Based on Genome-Wide DNA Methylation of Chinese Patients with Graves' Orbitopathy.BioMed research international · 2019Article
- Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2019Article
- Altered functional network connectivity relates to motor development in children born very preterm.NeuroImage · 2018Article
- Correlated Gene Expression and Anatomical Communication Support Synchronized Brain Activity in the Mouse Functional Connectome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.BMC genomics · 2017Article
- Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenome wide association studies (GWAS) are applied to identify genetic loci, which are associated with complex traits and human diseases. Analogous to the evolution of gene expression analyses, pathway analyses have emerged as important tools to uncover functional networks of genome-wide association data. Usually, pathway analyses combine statistical methods with a priori available biological knowledge. To determine significance thresholds for associated pathways, correction for multiple testing and over-representation permutation testing is applied.
resultsWe systematically investigated the impact of three different permutation test approaches for over-representation analysis to detect false positive pathway candidates and evaluate them on genome-wide association data of Dilated Cardiomyopathy (DCM) and Ulcerative Colitis (UC). Our results provide evidence that the gold standard - permuting the case-control status - effectively improves specificity of GWAS pathway analysis. Although permutation of SNPs does not maintain linkage disequilibrium (LD), these permutations represent an alternative for GWAS data when case-control permutations are not possible. Gene permutations, however, did not add significantly to the specificity. Finally, we provide estimates on the required number of permutations for the investigated approaches.
conclusionsTo discover potential false positive functional pathway candidates and to support the results from standard statistical tests such as the Hypergeometric test, permutation tests of case control data should be carried out. The most reasonable alternative was case-control permutation, if this is not possible, SNP permutations may be carried out. Our study also demonstrates that significance values converge rapidly with an increasing number of permutations. By applying the described statistical framework we were able to discover axon guidance, focal adhesion and calcium signaling as important DCM-related pathways and Intestinal immune network for IgA production as most significant UC pathway.
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