ArticleEuropean journal of epidemiology2013
Distinguishing true from false positives in genomic studies: p values.
Article in European journal of epidemiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Pooled it
- The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Pooled it
- GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.The journals of gerontology. Series A, Biological sciences and medical sciences · 2015Pooled it
- Integrating the environmental and genetic architectures of aging and mortality.Nature medicine · 2025Article
- Large-scale phenogenomic analysis of human cancers uncovers frequent alterations affecting SMC5/6 complex components in breast cancer.NAR cancer · 2023Article
- Lung cancer is also a hereditary disease.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Article
- Sources of bias in genomics research of oral and dental traits.Community dental health · 2020Review
- Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer's Disease or Depressive Disorder.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Interpretation of gene associations with risk of acute respiratory distress syndrome: P values, Bayes factors, positive predictive values, and need for replication.Critical care (London, England) · 2016Article
- Article
- The Rotterdam Study: 2016 objectives and design update.European journal of epidemiology · 2015Article
- Genetics and brain morphology.Neuropsychology review · 2015Article
- Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease.Trends in neurosciences · 2014Review
- GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database.Bioinformatics (Oxford, England) · 2014Article
- Integrative genomic analysis for the discovery of biomarkers in prostate cancer.Biomarker insights · 2014Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Distinguishing true from false positive findings is a major challenge in human genetic epidemiology. Several strategies have been devised to facilitate this, including the positive predictive value (PPV) and a set of epidemiological criteria, known as the "Venice" criteria. The PPV measures the probability of a true association, given a statistically significant finding, while the Venice criteria grade the credibility based on the amount of evidence, consistency of replication and protection from bias. A vast majority of journals use significance thresholds to identify the true positive findings. We studied the effect of p value thresholds on the PPV and used the PPV and Venice criteria to define usable thresholds of statistical significance. Theoretical and empirical analyses of data published on AlzGene show that at a nominal p value threshold of 0.05 most "positive" findings will turn out to be false if the prior probability of association is below 0.10 even if the statistical power of the study is higher than 0.80. However, in underpowered studies (0.25) with a low prior probability of 1 × 10(-3), a p value of 1 × 10(-5) yields a high PPV (>96 %). Here we have shown that the p value threshold of 1 × 10(-5) gives a very strong evidence of association in almost all studies. However, in the case of a very high prior probability of association (0.50) a p value threshold of 0.05 may be sufficient, while for studies with very low prior probability of association (1 × 10(-4); genome-wide association studies for instance) 1 × 10(-7) may serve as a useful threshold to declare significance.
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