ArticleAmerican journal of human genetics2008
Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 5 of them syntheses that pooled it.
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Who cites it
197 citing papers in PubMed, 5 syntheses or guidelines pooled it, 339 citations in OpenAlex.
- The Shared Genetic Architectures Between Lung Cancer and Multiple Polygenic Phenotypes in Genome-Wide Association Studies.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Pooled it
- Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.PloS one · 2019Pooled it
- Meta-analysis of gene-level associations for rare variants based on single-variant statistics.American journal of human genetics · 2013Pooled it
- A genome-wide association study on African-ancestry populations for asthma.The Journal of allergy and clinical immunology · 2010Pooled it
- Meta-analysis of genome-wide linkage studies across autoimmune diseases.European journal of human genetics : EJHG · 2009Pooled it
- High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Next-generation SNPs from lignin biosynthesis gene and transcription factors reveal a hidden teak (Frontiers in genetics · 2026Article
- Pharmacogenomic heterogeneity ofAnnals of medicine · 2025Observational
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 2025Review
- Germline predisposition in multiple myeloma.iScience · 2025Article
- Unifying approaches from statistical genetics and phylogenetics for mapping phenotypes in structured populations.PLoS biology · 2024Article
- Association of Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.Biochemical genetics · 2024Review
- Rare variants analyses suggest novel cleft genes in the African population.Scientific reports · 2024Article
- Phenotypic and genetic characterization of unexplored, potential cattle population of Madhya Pradesh.Tropical animal health and production · 2024Article
- Rare Variants Analyses Suggest Novel Cleft Genes in the African Population.Research square · 2024Article
- Article
- Schizophrenia in the genetic era: a review from development history, clinical features and genomic research approaches to insights of susceptibility genes.Metabolic brain disease · 2024Review
- Distortion of Mendelian segregation across the Angus cattle genome uncovering regions affecting reproduction.Scientific reports · 2023Article
- Unravelling transmission ratio distortion across the bovine genome: identification of candidate regions for reproduction defects.BMC genomics · 2023Article
- High-throughput sequencing analysis of nuclear-encoded mitochondrial genes reveals a genetic signature of human longevity.GeroScience · 2023Article
137 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Currently, single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) of >5% are preferentially used in case-control association studies of common human diseases. Recent technological developments enable inexpensive and accurate genotyping of a large number of SNPs in thousands of cases and controls, which can provide adequate statistical power to analyze SNPs with MAF <5%. Our purpose was to determine whether evaluating rare SNPs in case-control association studies could help identify causal SNPs for common diseases. We suggest that slightly deleterious SNPs (sdSNPs) subjected to weak purifying selection are major players in genetic control of susceptibility to common diseases. We compared the distribution of MAFs of synonymous SNPs with that of nonsynonymous SNPs (1) predicted to be benign, (2) predicted to be possibly damaging, and (3) predicted to be probably damaging by PolyPhen. Our sources of data were the International HapMap Project, ENCODE, and the SeattleSNPs project. We found that the MAF distribution of possibly and probably damaging SNPs was shifted toward rare SNPs compared with the MAF distribution of benign and synonymous SNPs that are not likely to be functional. We also found an inverse relationship between MAF and the proportion of nsSNPs predicted to be protein disturbing. On the basis of this relationship, we estimated the joint probability that a SNP is functional and would be detected as significant in a case-control study. Our analysis suggests that including rare SNPs in genotyping platforms will advance identification of causal SNPs in case-control association studies, particularly as sample sizes increase.
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