SynthesisG3 (Bethesda, Md.)2021
Revisiting the genome-wide significance threshold for common variant GWAS.
Synthesis in G3 (Bethesda, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 5 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS meta-analysis, biological network construction, and structural modeling.Scientific reports · 2025Pooled it
- Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis.Journal of translational medicine · 2025Pooled it
- Pooled it
- Genome-wide association study of preserved ratio impaired spirometry (PRISm).The European respiratory journal · 2024Pooled it
- X-linked genes influence various complex traits in dairy cattle.BMC genomics · 2023Pooled it
- Aphanomyces euteiches causes disease in Lathyrus sativus with a globally diverse, polygenic resistance landscape.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2026Article
- Multi-omics integration uncovers epigenetic control of metabolic reprogramming in triple-negative breast cancer.Journal of the Egyptian National Cancer Institute · 2026Article
- Local Trade-Offs Shape Flower Size Evolution Across Arabidopsis thaliana Distribution.Molecular ecology · 2026Article
- A module-based approach for post-omics, post-GWAS network-based gene classification.Bioinformatics (Oxford, England) · 2026Article
- A Human Pharmacogenomics Approach Provides Insight Into the Pathogenesis and Pathophysiology of Steroid-Induced Ocular Hypertension.Ophthalmology science · 2026Article
- Sheep erythrocyte potassium locus highlights MYADM family regulation of electroneutral potassium chloride cotransporters (KCC).BMC genomics · 2026Article
- Genetically supported drug target prioritization for rare diseases.Genome medicine · 2026Article
- A decade of discovery: Leveraging genomic data in the ABCD study to illuminate adolescent neurodevelopment.Developmental cognitive neuroscience · 2026Review
- Sex-specific roles of insulin-like growth factor-1, lean mass and fat mass in type 2 diabetes prevention: Mendelian randomization studies in Western and East Asian populations.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Population-Specific Genetic and Non-Genetic Influences on Sleep Traits and Health Outcomes.ArXiv · 2026Article
- Genome-Wide Identification of Genomic Regions Associated with Body Weight and Morphometric Traits in Awassi Sheep.Animals : an open access journal from MDPI · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- The Genetic and Morphological Basis of Local Adaptation to Elevational Extremes in an Alpine Finch.Ecology and evolution · 2026Article
- Polygenic risk scores: Navigating the future of precision medicine through economic, ethical, and scientific advancements.iScience · 2026Review
- Beyond Single Variants: A Pathway-Based Approach to Explore the Genetic Basis of Memory.Molecular neurobiology · 2026Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Over the last decade, GWAS meta-analyses have used a strict P-value threshold of 5 × 10-8 to classify associations as significant. Here, we use our current understanding of frequently studied traits including lipid levels, height, and BMI to revisit this genome-wide significance threshold. We compare the performance of studies using the P = 5 × 10-8 threshold in terms of true and false positive rate to other multiple testing strategies: (1) less stringent P-value thresholds, (2) controlling the FDR with the Benjamini-Hochberg and Benjamini-Yekutieli procedure, and (3) controlling the Bayesian FDR with posterior probabilities. We applied these procedures to re-analyze results from the Global Lipids and GIANT GWAS meta-analysis consortia and supported them with extensive simulation that mimics the empirical data. We observe in simulated studies with sample sizes ∼20,000 and >120,000 that relaxing the P-value threshold to 5 × 10-7 increased discovery at the cost of 18% and 8% of additional loci being false positive results, respectively. FDR and Bayesian FDR are well controlled for both sample sizes with a few exceptions that disappear under a less stringent definition of true positives and the two approaches yield similar results. Our work quantifies the value of using a relaxed P-value threshold in large studies to increase their true positive discovery but also show the excess false positive rates due to such actions in modest-sized studies. These results may guide investigators considering different thresholds in replication studies and downstream work such as gene-set enrichment or pathway analysis. Finally, we demonstrate the viability of FDR-controlling procedures in GWAS.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.