ArticleHGG advances2023
Inverted genomic regions between reference genome builds in humans impact imputation accuracy and decrease the power of association testing.
Article in HGG advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups.Nature genetics · 2025Pooled it
- Transcriptome-wide association studies implicate RCC1 and PHACTR4 in prostate cancer survival.European journal of human genetics : EJHG · 2026Article
- Incorporating dietary information to enhance polygenic prediction models with applications to body mass index and type 2 diabetes.Genes & nutrition · 2026Article
- Pharmacogenomic predictors of drug response and choice in dyslipidemia and hypertension.medRxiv : the preprint server for health sciences · 2026Article
- High-quality Population-specific Haplotype-resolved Reference Panel in the Genomic and Pangenomic Eras.Genomics, proteomics & bioinformatics · 2025Review
- Polygenic risk score for type 2 diabetes shows context-dependent effects across populations.Nature communications · 2025Article
- Genetic analyses of eight complex diseases using predicted continuous representations of disease.Cell reports methods · 2025Article
- Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study.Circulation. Heart failure · 2025Article
- The accuracy of polygenic score models for BMI and Type II diabetes in the Native Hawaiian population.Communications biology · 2025Article
- A likelihood-based framework for demographic inference from genealogical trees.Nature genetics · 2025Article
- Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.International journal of molecular sciences · 2024Article
- Imputation accuracy across global human populations.American journal of human genetics · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Over the last two decades, the human reference genome has undergone multiple updates as we complete a linear representation of our genome. Two versions of human references are currently used in the biomedical literature, GRCh37/hg19 and GRCh38. Conversions between these versions are critical for quality control, imputation, and association analysis. In the present study, we show that single-nucleotide variants (SNVs) in regions inverted between different builds of the reference genome are often mishandled bioinformatically. Depending on the array type, SNVs are found in approximately 2-5 Mb of the genome that are inverted between reference builds. Coordinate conversions of these variants are mishandled by both the TOPMed imputation server as well as routine in-house quality control pipelines, leading to underrecognized downstream analytical consequences. Specifically, we observe that undetected allelic conversion errors for palindromic (i.e., A/T or C/G) variants in these inverted regions would destabilize the local haplotype structure, leading to loss of imputation accuracy and power in association analyses. Though only a small proportion of the genome is affected, these regions include important disease susceptibility variants that would be affected. For example, the p value of a known locus associated with prostate cancer on chromosome 10 (chr10) would drop from 2.86 × 10
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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 Socratic graph.