ArticleGenetic epidemiology2011
Confounded by sequencing depth in association studies of rare alleles.
Article in Genetic epidemiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed.
- Evaluating Bioinformatics Processing of Somatic Variant Detection in cfDNA Using Targeted Sequencing with UMIs.International journal of molecular sciences · 2024Article
- RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.Genome biology · 2020Article
- Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel.European urology · 2019Article
- Genomic Prediction in Tetraploid Ryegrass Using Allele Frequencies Based on Genotyping by Sequencing.Frontiers in plant science · 2018Article
- Exome Analysis of Rare and Common Variants within the NOD Signaling Pathway.Scientific reports · 2017Article
- Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study.Genetic epidemiology · 2017Article
- Estimating genomic heritabilities at the level of family-pool samples of perennial ryegrass using genotyping-by-sequencing.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2016Article
- A statistical approach for rare-variant association testing in affected sibships.American journal of human genetics · 2015Article
- Article
- Value of Mendelian laws of segregation in families: data quality control, imputation, and beyond.Genetic epidemiology · 2014Article
- Association analysis using next-generation sequence data from publicly available control groups: the robust variance score statistic.Bioinformatics (Oxford, England) · 2014Article
- Jumping on the Train of Personalized Medicine: A Primer for Non-Geneticist Clinicians: Part 2. Fundamental Concepts in Genetic Epidemiology.Current psychiatry reviews · 2014Article
- A1180V of cardiac sodium channel gene (SCN5A): is it a risk factor for dilated cardiomyopathy or just a common variant in Han Chinese?Disease markers · 2013Article
- Re-ranking sequencing variants in the post-GWAS era for accurate causal variant identification.PLoS genetics · 2013Article
- A flexible likelihood framework for detecting associations with secondary phenotypes in genetic studies using selected samples: application to sequence data.European journal of human genetics : EJHG · 2012Article
- Computational and statistical approaches to analyzing variants identified by exome sequencing.Genome biology · 2011Review
- Estimation of allele frequency and association mapping using next-generation sequencing data.BMC bioinformatics · 2011Article
- Assessing the impact of non-differential genotyping errors on rare variant tests of association.Human heredity · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Next-generation DNA sequencing technologies are facilitating large-scale association studies of rare genetic variants. The depth of the sequence read coverage is an important experimental variable in the next-generation technologies and it is a major determinant of the quality of genotype calls generated from sequence data. When case and control samples are sequenced separately or in different proportions across batches, they are unlikely to be matched on sequencing read depth and a differential misclassification of genotypes can result, causing confounding and an increased false-positive rate. Data from Pilot Study 3 of the 1000 Genomes project was used to demonstrate that a difference between the mean sequencing read depth of case and control samples can result in false-positive association for rare and uncommon variants, even when the mean coverage depth exceeds 30× in both groups. The degree of the confounding and inflation in the false-positive rate depended on the extent to which the mean depth was different in the case and control groups. A logistic regression model was used to test for association between case-control status and the cumulative number of alleles in a collapsed set of rare and uncommon variants. Including each individual's mean sequence read depth across the variant sites in the logistic regression model nearly eliminated the confounding effect and the inflated false-positive rate. Furthermore, accounting for the potential error by modeling the probability of the heterozygote genotype calls in the regression analysis had a relatively minor but beneficial effect on the statistical results.
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.