Categoría: The American Journal of Human Genetics
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Genetic regulation of the plasma proteome and its link to cardiometabolic disease in Greenlandic Inuit
We conducted a protein quantitative trait locus (pQTL) study in 3,707 Greenlanders, identifying 251 associations, including 70 novel signals. We compared variance explained with Europeans from the UK Biobank, linked pQTLs to cardiovascular outcomes, an…
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A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease
Current methods for detecting splicing quantitative trait loci (sQTLs) miss many disease-associated genetic variants. MAJIQTL introduces improved statistical modeling and comprehensive splicing representation, discovering significantly more functionall…
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De novo variants in ATP2B1 lead to neurodevelopmental delay
(The American Journal of Human Genetics 109, 944–952; May 5, 2022)
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This month in The Journal
Rare diseases affect more than 5% of the population in the United States. Classically, rare diseases are diagnosed through a phenotype-first approach in which individuals with distinct clinical features undergo genetic testing to identify the underlyin…
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Lessons learned: Recommendations for reproducible paleogenomic data analyses
Souilmi et al. propose essential guidelines to improve the reproducibility of paleogenomic data analysis. As ancient DNA research often relies on the destructive sampling of finite resources, these recommendations for data formatting, metadata reportin…
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Origins and implications of intron retention quantitative trait loci in human tissues
Intron retention is an important form of RNA variation. We mapped intron retention quantitative trait loci (irQTLs) in human tissues. irQTLs can generate expression quantitative trait loci (eQTLs) through the nonsense-mediated decay pathway. eQTLs can …
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How to create personalized gene editing platforms: Next steps toward interventional genetics
How do we go from a single individual receiving a personalized gene-editing therapy to a future of “interventional genetics” in which such therapies are the standard of care? First and foremost: regulatory innovation.
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The Clinical Pharmacogenetics Implementation Consortium’s consensus-based framework for assigning allele function
The Clinical Pharmacogenetics Implementation Consortium (CPIC) is dedicated to integrating pharmacogenetic testing into clinical practice by developing and disseminating peer-reviewed, evidence-based gene-drug clinical practice guidelines. A critical c…
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BRCA1-, BRCA2-, and PALB2-related Fanconi anemia: Scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes
The recessive Fanconi anemia phenotype is used to classify BRCA1, BRCA2, and PALB2 variants with respect to dominant hereditary breast-ovarian cancer syndrome. Phenotype-genotype analysis of 178 individuals bi-allelic for BRCA1, BRCA2, or PALB2 pathoge…
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Using the ancestral recombination graph to study the history of rare variants in founder populations
This study statistically traces the transmission history of rare alleles within genealogies to impute carrier status and regional allele frequencies. It uses the approach to find that imputed carriers for recessive variant LPL:c.701C>T have a heterozyg…