The American Journal of Human Genetics - 2024

222 articles | Last updated: 2025-12-03 14:12:57
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T A T A T A T A
A missense variant effect map for the human tumor-suppressor protein CHK2
This month in The Journal
Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial
Genomic medicine year in review: 2024
Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection
The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk
Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis
Employing effective recruitment and retention strategies to engage a diverse pediatric population in genomics research
Inherited infertility: Mapping loci associated with impaired female reproduction
The PRIMED Consortium: Reducing disparities in polygenic risk assessment
Comparative analysis of predicted DNA secondary structures infers complex human centromere topology
Toward trustable use of machine learning models of variant effects in the clinic
Monoallelic pathogenic variants in LEPR do not cause obesity
Allele frequency impacts the cross-ancestry portability of gene expression prediction in lymphoblastoid cell lines
Local genetic correlation via knockoffs reduces confounding due to cross-trait assortative mating
Proteome-wide Mendelian randomization and functional studies uncover therapeutic targets for polycystic ovarian syndrome
Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly
An abdominal obesity missense variant in the adipocyte thermogenesis gene TBX15 is implicated in adaptation to cold in Finns
This month in The Journal
Genomes and epigenomes of matched normal and tumor breast tissue reveal diverse evolutionary trajectories and tumor-host interactions
GPS-Net: Discovering prognostic pathway modules based on network regularized kernel learning
3D genome topology distinguishes molecular subgroups of medulloblastoma
Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia
Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression
Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags
Inverse relationship between polygenic risk burden and age of onset of autoimmune vitiligo
MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway
Where is the boundary of the human pseudoautosomal region?
Profiling genetically driven alternative splicing across the Indonesian archipelago
Recognizing trainees: The AJHG Award for Outstanding Trainee Publication
Joint testing of rare variant burden scores using non-negative least squares
This month in The Journal
Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies
Modeling recent positive selection using identity-by-descent segments
Large-scale application of ClinGen-InSiGHT APC-specific ACMG/AMP variant classification criteria leads to substantial reduction in VUS
Phenotypic spectrum of dual diagnoses in developmental disorders
Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants
Disentangling mechanisms behind the pleiotropic effects of proximal 16p11.2 BP4-5 CNVs
The pleiotropic spectrum of proximal 16p11.2 CNVs
Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants
Toward building a comprehensive human pan-genome: The SEN-GENOME project
Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia
Somatic mutations in arteriovenous malformations in hereditary hemorrhagic telangiectasia support a bi-allelic two-hit mutation mechanism of pathogenesis
International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review
The BabySeq Project: A clinical trial of genome sequencing in a diverse cohort of infants
Germline polygenic risk scores are associated with immune gene expression signature and immune cell infiltration in breast cancer
Semi-supervised machine learning method for predicting homogeneous ancestry groups to assess Hardy-Weinberg equilibrium in diverse whole-genome sequencing studies homogeneous ancestry groups
Alu insertion-mediated dsRNA structure formation with pre-existing Alu elements as a disease-causing mechanism
Genetic modifiers of body mass index in individuals with cystic fibrosis
Assessing the utility of large language models for phenotype-driven gene prioritization in the diagnosis of rare genetic disease
The methodological and ethical concerns of genetic studies of same-sex sexual behavior
All of Us Research Program year in review: 2023–2024
A new annual feature of AJHG: All of Us Research Program year in review
Implementation of a dyadic nomenclature for monogenic diseases
This Month in The Journal
Hearing restoration by gene replacement therapy for a multisite-expressed gene in a mouse model of human DFNB111 deafness
Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications
Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa
ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification
SpliceVarDB: A comprehensive database of experimentally validated human splicing variants
Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression
Genes with differential expression across ancestries are enriched in ancestry-specific disease effects likely due to gene-by-environment interactions
Inflation of polygenic risk scores caused by sample overlap and relatedness: Examples of a major risk of bias
Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis
Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/β-catenin signaling
Liver eQTL meta-analysis illuminates potential molecular mechanisms of cardiometabolic traits
Calibration of variant effect predictors on genome-wide data masks heterogeneous performance across genes
Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel
Evaluating large language models on medical, lay-language, and self-reported descriptions of genetic conditions
Genetic effects on the skin methylome in healthy older twins
Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma
This Month in The Journal
SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline
A novel multivariable Mendelian randomization framework to disentangle highly correlated exposures with application to metabolomics
Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder
Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset
Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations
RNA variant assessment using transactivation and transdifferentiation
Omnibus proteome-wide association study identifies 43 risk genes for Alzheimer disease dementia
Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain
Long-read proteogenomics to connect disease-associated sQTLs to the protein isoform effectors of disease
Benchmarking Mendelian randomization methods for causal inference using genome-wide association study summary statistics
Ornaments for efficient allele-specific expression estimation with bias correction
De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder
An integrative multi-context Mendelian randomization method for identifying risk genes across human tissues
Inferring causal direction between two traits using R2 with application to transcriptome-wide association studies
Misexpression of inactive genes in whole blood is associated with nearby rare structural variants
Functional characterization of 2,832 JAG1 variants supports reclassification for Alagille syndrome and improves guidance for clinical variant interpretation
JASPER: Fast, powerful, multitrait association testing in structured samples gives insight on pleiotropy in gene expression
Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome
Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes
Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B
Charting a landmark-driven path forward for population genetics and ancient DNA research in Africa
The 2023 Distinguished Speakers Symposium: The future of human genetics and genomics
The 2023 Distinguished Speakers Symposium: Closing Remarks
From complete genomes to pangenomes
This Month in The Journal
Exploring the noncoding genome with chromosomal structural rearrangements
The DARC side of genetics in cancer: Breast cancer disparities
Eugenics and the misuse of Mendel
Ensuring best practice in genomics education: A scoping review of genomics education needs assessments and evaluations
Ensuring best practice in genomics education: A theory- and empirically informed evaluation framework
Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia
A transcriptomic atlas of the human brain reveals genetically determined aspects of neuropsychiatric health
GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas
High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility
Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes
Evaluation of polygenic scoring methods in five biobanks shows larger variation between biobanks than methods and finds benefits of ensemble learning
Identification and correction for collider bias in a genome-wide association study of diabetes-related heart failure
Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita
A scalable and robust variance components method reveals insights into the architecture of gene-environment interactions underlying complex traits
PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response
This Month in The Journal
CanCellVar: A database for single-cell variants map in human cancer
The impact of clinical genome sequencing in a global population with suspected rare genetic disease
Impact of genome build on RNA-seq interpretation and diagnostics
KnockoffHybrid: A knockoff framework for hybrid analysis of trio and population designs in genome-wide association studies
Regional-specific calibration enables application of computational evidence for clinical classification of 5′ cis-regulatory variants in Mendelian disease
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature
Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants
The impact of inversions across 33,924 families with rare disease from a national genome sequencing project
Oral and non-oral lichen planus show genetic heterogeneity and differential risk for autoimmune disease and oral cancer
Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity
Genome-wide DNA methylation changes in human spermatogenesis
An integrative framework to prioritize genes in more than 500 loci associated with body mass index
Joint host-pathogen genomic analysis identifies hepatitis B virus mutations associated with human NTCP and HLA class I variation
De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features
Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease
Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect
A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer
Cis- and trans-eQTL TWASs of breast and ovarian cancer identify more than 100 susceptibility genes in the BCAC and OCAC consortia
Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
shaPRS: Leveraging shared genetic effects across traits or ancestries improves accuracy of polygenic scores
A powerful approach to identify replicable variants in genome-wide association studies
This Month in The Journal
Potential corporate uses of polygenic indexes: Starting a conversation about the associated ethics and policy issues
Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans
Mutations in TOP3A Cause a Bloom Syndrome-like Disorder
Telomere-lengthening germline variants predispose to a syndromic papillary thyroid cancer subtype
Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network
Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis
Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds
MagicalRsq-X: A cross-cohort transferable genotype imputation quality metric
Genomic Answers for Kids: Toward more equitable access to genomic testing for rare diseases in rural populations
CAG repeat mosaicism is gene specific in spinocerebellar ataxias
A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens
Toward clinical exomes in diagnostics and management of male infertility
A new test for trait mean and variance detects unreported loci for blood-pressure variation
Imputation accuracy across global human populations
The clinical utility and diagnostic implementation of human subject cell transdifferentiation followed by RNA sequencing
Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors
Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase
This Month in The Journal
Many roads to a gene-environment interaction
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease
De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features
Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
Biobank-scale inference of multi-individual identity by descent and gene conversion
Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic
Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation
Expanding the PRAAS spectrum: De novo mutations of immunoproteasome subunit β-type 10 in six infants with SCID-Omenn syndrome
The association of cigarette smoking with DNA methylation and gene expression in human tissue samples
Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates
Guidance on use of race, ethnicity, and geographic origin as proxies for genetic ancestry groups in biomedical publications
De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features
Investigating the potential of single-cell DNA methylation data to detect allele-specific methylation and imprinting
2023 ASHG Scientific Achievement Award: Molly Przeworski
2023 ASHG Leadership Award
2023 ASHG awards and addresses
2023 ASHG Lifetime Achievement Award: Neil Risch
2023 ASHG Scientific Achievement Award
2023 ASHG Leadership Award: Nancy Cox
This Month in The Journal
2023 ASHG presidential address—Reflecting on our 75 years: Acknowledging our past, embracing our present, and dreaming about our future
STIGMA: Single-cell tissue-specific gene prioritization using machine learning
2023 ASHG Lifetime Achievement Award: “If you want to go fast, go alone; if you want to go far, go together”
Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models
Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy
Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain
Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability
De novo variants in DENND5B cause a neurodevelopmental disorder
Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA
Epigenome-wide association study of total nicotine equivalents in multiethnic current smokers from three prospective cohorts
The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function
The cells of the sensory epithelium, and not the stria vascularis, are the main cochlear cells related to the genetic pathogenesis of age-related hearing loss
Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt
Transcriptome-wide association study of the plasma proteome reveals cis and trans regulatory mechanisms underlying complex traits
Insights into the mechanisms and structure of breakage-fusion-bridge cycles in cervical cancer using long-read sequencing
This Month in The Journal
Cell-type deconvolution of bulk-blood RNA-seq reveals biological insights into neuropsychiatric disorders
Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants
CRISPR activation to characterize splice-altering variants in easily accessible cells
Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction
Role of CAMK2D in neurodevelopment and associated conditions
Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements
A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy
Regulatory features aid interpretation of 3′UTR variants
Adaptation of a mutual exclusivity framework to identify driver mutations within oncogenic pathways
The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK ancestry
STIGMA: Single-cell tissue-specific gene prioritization using machine learning
A comprehensive analysis of clinical and polygenic germline influences on somatic mutational burden
Systematic identification of genotype-dependent enhancer variants in eosinophilic esophagitis
75 years of The American Journal of Human Genetics
omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases
A Bayesian approach to Mendelian randomization using summary statistics in the univariable and multivariable settings with correlated pleiotropy
Genetic determinants of IgG antibody response to COVID-19 vaccination
Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine
An interactive atlas of three-dimensional syndromic facial morphology
Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
This Month in The Journal
A Bayesian fine-mapping model using a continuous global-local shrinkage prior with applications in prostate cancer analysis
A recurrent de novo MAX p.Arg60Gln variant causes a syndromic overgrowth disorder through differential expression of c-Myc target genes
A statistical method for image-mediated association studies discovers genes and pathways associated with four brain disorders
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome
ClinGen guidance for use of the PP1/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification
Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases
Will variants of uncertain significance still exist in 2030?
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease