ArticleGenome medicine2015
Rare variant association studies: considerations, challenges and opportunities.
Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 4 of them syntheses that pooled it.
What it found
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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.
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Who cites it
138 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Gene-based association analysis of depression risk among European ancestry Parkinson's disease patients.Human genetics · 2026Pooled it
- Scalable and accurate rare variant meta-analysis with Meta-SAIGE.Nature genetics · 2025Pooled it
- The Role of Genetics in Stroke Risk and Outcome: A Review of Current Evidence.Brain and behavior · 2025Pooled it
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- T-rex: standardized analysis of germline variants in whole-exome sequencing trios.Scientific reports · 2026Article
- An empirical Bayes framework for burden and dispersion association tests helps prioritize rare variants associated with Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Genetic Determinants of T-Cell Homeostasis in Critical Illness: An Exploratory Analysis of Immune Gene Variants and TREC Dynamics.Journal of personalized medicine · 2026Article
- Functional insights into dispensable genes using genome-wide loss-of-function burden tests in Arabidopsis.The Plant cell · 2026Article
- Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants.GeroScience · 2026Article
- Genome-wide association analyses for growth, carcass composition, and meat quality traits of Iberian pigs fattened in free open air.Journal of animal science · 2026Article
- BeyondFrontiers in genetics · 2026Review
- Burden of rare genetic variants in genes associated with cancer among Malawian cervical cancer patients.African journal of laboratory medicine · 2026Article
- Unsupervised machine learning integrates genomic variants and EMR to unravel mechanisms of brain hemorrhage and epilepsy as early indicators of Alzheimer's in down syndrome.Alzheimer's research & therapy · 2025Article
- Review
- Decades' progress and prospects on maize functional genomics and molecular breeding.Science China. Life sciences · 2025Review
- Utilising genomic association data for causal inference in anorexia nervosa.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Estimation of demography and mutation rates from one million haploid genomes.American journal of human genetics · 2025Article
- Leveraging functional annotations to map rare variants associated with Alzheimer disease with gruyere.American journal of human genetics · 2025Article
- Increased burden of rare variants in GWAS associated genes in familial multiple sclerosis.Scientific reports · 2025Article
- GWAS scorecard prioritizes kidney genes using coding and regulatory variants.Nature reviews. Nephrology · 2025Article
78 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
2 authors.
Funding
Abstract
Genome-wide association studies (GWASs) have successfully uncovered thousands of robust associations between common variants and complex traits and diseases. Despite these successes, much of the heritability of these traits remains unexplained. Because low-frequency and rare variants are not tagged by conventional genome-wide genotyping arrays, they may represent an important and understudied component of complex trait genetics. In contrast to common variant GWASs, there are many different types of study designs, assays and analytic techniques that can be utilized for rare variant association studies (RVASs). In this review, we briefly present the different technologies available to identify rare genetic variants, including novel exome arrays. We also compare the different study designs for RVASs and argue that the best design will likely be phenotype-dependent. We discuss the main analytical issues relevant to RVASs, including the different statistical methods that can be used to test genetic associations with rare variants and the various bioinformatic approaches to predicting in silico biological functions for variants. Finally, we describe recent rare variant association findings, highlighting the unexpected conclusion that most rare variants have modest-to-small effect sizes on phenotypic variation. This observation has major implications for our understanding of the genetic architecture of complex traits in the context of the unexplained heritability challenge.
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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.