ArticleBMJ (Clinical research ed.)2021
Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation.
Article in BMJ (Clinical research ed.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Opportunistic Screening of High-Risk Breast Cancer Variants in Hospital Biobank Setting.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Integrated Cross-Platform Analysis Reveals Candidate Variants and Linkage Disequilibrium-Defined Loci Associated with Osteoporosis in Korean Postmenopausal Women.Diagnostics (Basel, Switzerland) · 2026Article
- Severe obesity as an oligogenic condition: evidence from 1714 adults seeking treatment in the UK National Health Service.Human genomics · 2025Article
- Acceptability, consideration, intention, and uptake of six common types of direct-to-consumer genetic tests in the Netherlands.Journal of genetic counseling · 2025Article
- The multifaceted role of RNF213 in oncogenesis: current insights and future research directions.Discover oncology · 2025Review
- Identifying individuals with rare disease variants by inferring shared ancestral haplotypes from SNP array data.NAR genomics and bioinformatics · 2025Article
- Detection of distant relatedness in biobanks to identify undiagnosed cases of Mendelian disease as applied to Long QT syndrome.Nature communications · 2024Article
- Application of the TaqMan ARMS-PCR Approach for Genotyping Drug-Induced Hearing Loss Using Dried Blood Samples.Current issues in molecular biology · 2024Article
- Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis.World journal of gastrointestinal oncology · 2024Article
- Penetrance and expressivity of mitochondrial variants in a large clinically unselected population.Human molecular genetics · 2024Article
- Exome sequencing of UK birth cohorts.Wellcome open research · 2024Article
- Low-Cost High-Throughput Genotyping for Diagnosing Familial Hypercholesterolemia.Circulation. Genomic and precision medicine · 2023Article
- Influence of family history on penetrance of hereditary cancers in a population setting.EClinicalMedicine · 2023Article
- Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.JCO precision oncology · 2023Article
- Review
- The necessity of incorporating non-genetic risk factors into polygenic risk score models.Scientific reports · 2023Article
- Screening for potential undiagnosed Gaucher disease patients: Utilisation of the Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS) in conjunction with electronic health record data, tissue specimens, and small nucleotide polymorphism (SNP) genotype data available in Finnish biobanks.Molecular genetics and metabolism reports · 2022Article
- Analysis of clinically relevant variants from ancestrally diverse Asian genomes.Nature communications · 2022Article
- Array genotyping as diagnostic approach in medical genetics.Molecular genetics & genomic medicine · 2022Article
- The impact of Mendelian sleep and circadian genetic variants in a population setting.PLoS genetics · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population.
designRetrospective, population based diagnostic evaluation.
participants49 908 people recruited to the UK Biobank with SNP chip and next generation sequencing data, and an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.
main outcome measuresGenotyping (that is, identification of the correct DNA base at a specific genomic location) using SNP chips versus sequencing, with results split by frequency of that genotype in the population. Rare pathogenic variants in the
resultsOverall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data. Results were similar for SNP chip data from the Personal Genome Project, and 20/21 individuals analysed had at least one false positive rare pathogenic variant that had been incorrectly genotyped. For pathogenic variants in the
conclusionsSNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.
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