ReviewAmerican journal of human genetics2014
Rare-variant association analysis: study designs and statistical tests.
Review in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07587853 (Investigation of Pathogenic Variants in DNA Repair and Meiotic Genes Associated With Ovarian Reserve and Folliculogenesis in Idiopathic Premature Ovarian Insufficiency Using Whole Exome Sequencing), which is not on this map. Cited by 644 papers, 10 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.
Investigation of Pathogenic Variants in DNA Repair and Meiotic Genes Associated With Ovarian Reserve and Folliculogenesis in Idiopathic Premature Ovarian Insufficiency Using Whole Exome Sequencing: A Case-Control Study
Who cites it
644 citing papers in PubMed, 10 syntheses or guidelines pooled it.
- Empirically determined baseline masking strategies and other considerations for gene-level burden tests.Nature genetics · 2026Pooled it
- Host genetic factors modulating dengue virus: a systematic review of TLR polymorphisms.BMC infectious diseases · 2026Pooled it
- Computationally efficient meta-analysis of gene-based tests using summary statistics in large-scale genetic studies.Nature genetics · 2025Pooled it
- Rare-Variant Genome-Wide Association and Polygenic Score Assessment of Vitamin D Status in a Middle Eastern Population.International journal of molecular sciences · 2025Pooled it
- Correcting for Genomic Inflation Leads to Loss of Power in Large-Scale Genome-Wide Association Study Meta-Analysis.Genetic epidemiology · 2025Pooled it
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.Nature genetics · 2023Pooled it
- Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.Nature genetics · 2023Pooled it
- KDR genetic predictor of toxicities induced by sorafenib and regorafenib.The pharmacogenomics journal · 2022Pooled it
- Trans-Ethnic Meta-Analysis of Interactions Between Genetics and Early-Life Socioeconomic Context on Memory Performance and Decline in Older Americans.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Pooled it
- Trial
- Germline Variation and Somatic Alterations in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Article
- Rare variant effect estimation and polygenic risk prediction.Nature genetics · 2026Article
- Article
- Rare Germline Variants in Key Pathways Contribute to Hepatocellular Carcinoma Risk in Hispanic Individuals.Cancers · 2026Article
- Exome-wide association study reveals common and rare coding variants shaping chronic pain in 327,642 UK biobank participants.Genome medicine · 2026Article
- A combined study of whole-exome sequencing and structural neuroimaging markers in bipolar disorder.Translational psychiatry · 2026Article
- NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease.Cell genomics · 2026Article
- Defining Pseudo-Haplotype Analysis Reveals Multi-Gene Genetic Pattern Across BAF Chromatin Remodeling Complexes.bioRxiv : the preprint server for biology · 2026Article
584 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.
Funding
Abstract
Despite the extensive discovery of trait- and disease-associated common variants, much of the genetic contribution to complex traits remains unexplained. Rare variants can explain additional disease risk or trait variability. An increasing number of studies are underway to identify trait- and disease-associated rare variants. In this review, we provide an overview of statistical issues in rare-variant association studies with a focus on study designs and statistical tests. We present the design and analysis pipeline of rare-variant studies and review cost-effective sequencing designs and genotyping platforms. We compare various gene- or region-based association tests, including burden tests, variance-component tests, and combined omnibus tests, in terms of their assumptions and performance. Also discussed are the related topics of meta-analysis, population-stratification adjustment, genotype imputation, follow-up studies, and heritability due to rare variants. We provide guidelines for analysis and discuss some of the challenges inherent in these studies and future research directions.
Indexed as
Identifiers
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.