American Journal of Human Genetics

Article	Citations
This month in The Journal	525
2022 Curt Stern Award introduction: Heidi Rehm	479
This month in The Journal	283
Potential corporate uses of polygenic indexes: Starting a conversation about the associated ethics and policy issues	157
Mendelian randomization linking metabolites with enzymes reveals pathway regulation and therapeutic avenues	149
Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction	149
Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes	143
This month in The Journal	111
The Electronic Medical Records and Genomics study: Design and analytic framework for assessing the impact of genome-informed risk assessments	102
Best practices for improving alignment and variant calling on human sex chromosomes	100
Genomes and epigenomes of matched normal and tumor breast tissue reveal diverse evolutionary trajectories and tumor-host interactions	99
Fast and accurate Bayesian polygenic risk modeling with variational inference	95
Genetic control of non-coding RNAs in the human brain and their implications for complex traits	93
mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data	89
Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt	87
Measuring disease likelihood in genomic ascertainment	80
Genetic determinants of IgG antibody response to COVID-19 vaccination	79
Evaluating large language models on medical, lay-language, and self-reported descriptions of genetic conditions	77
“Choice of law” in precision medicine research	72
Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability	71
Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the “omnigenic” sparse effector hypothesis of complex trait genetics	69
Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA	69
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease	68
AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia	66
This Month in The Journal	65

Human leukocyte antigen variation is associated with cytomegalovirus serostatus in healthy individuals	63
Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples	63
Actionable genetic variants in 4,198 Scottish participants from the Orkney and Shetland founder populations and implementation of return of results	62
The impact of inversions across 33,924 families with rare disease from a national genome sequencing project	62
Improved detection of aberrant splicing with FRASER 2.0 and the intron Jaccard index	60
This month in The Journal	57
Neurodevelopmental copy-number variants: A roadmap to improving outcomes by uniting patient advocates, researchers, and clinicians for collective impact	57
Improving polygenic risk prediction performance by integrating electronic health records through phenotype embedding	56
Sequence variants in HECTD1 result in a variable neurodevelopmental disorder	56
Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus	52
Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants	52
2022 ASHG presidential address—One human race: Billions of genomes	51
shaPRS: Leveraging shared genetic effects across traits or ancestries improves accuracy of polygenic scores	51
This month in The Journal	47
A spectrum of recessiveness among Mendelian disease variants in UK Biobank	47
2022 Curt Stern Award: Advancing genomic medicine through collaboration and data sharing	47
Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags	47
To boldly go: Unpacking the NHGRI’s bold predictions for human genomics by 2030	46
2024 ASHG Scientific Achievement Award	46
Benchmarking Mendelian randomization methods for causal inference using genome-wide association study summary statistics	45
The ancestry and geographical origins of St Helena’s liberated Africans	45
A new annual feature of AJHG: All of Us Research Program year in review	45
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3	44
Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4	42
Using the ancestral recombination graph to study the history of rare variants in founder populations	42
Bi-allelic PRMT9 loss-of-function variants cause a syndromic form of intellectual disability	42
Transcriptome-wide association study of the plasma proteome reveals cis and trans regulatory mechanisms underlying complex traits	41
Literature-based predictions of Mendelian disease therapies	41
Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders	41
Structural biology in variant interpretation: Perspectives and practices from two studies	40
Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis	40
SpliceVarDB: A comprehensive database of experimentally validated human splicing variants	39
The association of cigarette smoking with DNA methylation and gene expression in human tissue samples	39
Addressing underrepresentation in genomics research through community engagement	38
Unraveling the impact of VHL exon 2 mutations in erythrocytosis or von Hippel-Lindau disease identified RNA-binding proteins involved in VHL splicing	38
Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts	38
Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications	37
2023 ASHG presidential address—Reflecting on our 75 years: Acknowledging our past, embracing our present, and dreaming about our future	37
SMN1 variants identified by false-positive SMA newborn screening tests: Therapeutic hurdles and functional and epidemiological solutions	37
Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention	37
This month in The Journal	37
This month in The Journal	37
Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background	37
A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens	36
Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models	36
Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations	36
BRCA1-, BRCA2-, and PALB2-related Fanconi anemia: Scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes	36
Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity	35
Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa	35
Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits	35

Exploring the omnigenic architecture of selected complex traits	34
Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy	34
Extremely early genomic events and temporal order of esophageal squamous cell carcinogenesis: Longitudinal self-comparison of progressors and non-progressors	34
Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications	34
Incorporating polygenic risk scores and social determinants of health across populations: Considerations and best practices in research	34
This Month in The Journal	33
A next-generation episignature for Kabuki syndrome enables fine mapping of the impact of KMT2D variants to inform precision medicine	33
Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies	33
Newborn screening for type 1 diabetes using genome-based risk scores in the Early Check program	33
The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function	33
Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites	33
Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common control subjects	32
COMPADRE: Combined pedigree-aware distant relatedness estimation for improved pedigree reconstruction	32
2025 ASHG awards and addresses	32
Demographic history and genetic variation of the Armenian population	32
Validation and context-dependent effects of a prostate cancer polygenic risk score in the All of Us Research Program	31
2022 William Allan Award introduction: Peter Donnelly	31
Functional classification of platelet gene variants using CRISPR HDR in CD34+ cell-derived megakaryocytes	31
The ancestry and geographical origins of St Helena’s liberated Africans	31
Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1	31
Liver single-nucleus multiome profiling reveals cell-type mechanisms for cardiometabolic traits	31
Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia	31
PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects	30
Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants	30
Significance tests for R2 of out-of-sample prediction using polygenic scores	30
LiMA: Robust inference of molecular mediation from summary statistics	30
A powerful approach to identify replicable variants in genome-wide association studies	30
Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome	30
Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies	30
Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation	30
The impact of sex on the immune system explored at the single-cell level	30
This month in The Journal	29
Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders	29
Inherited HTT CAG repeat length does not have a major impact on Huntington disease duration	29
Investigating the potential of single-cell DNA methylation data to detect allele-specific methylation and imprinting	28
Haplotype analysis reveals pleiotropic disease associations in the HLA region	28
Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome	28
Biobank-scale inference of multi-individual identity by descent and gene conversion	28
Trio RNA sequencing in a cohort of medically complex children	27
Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds	27
De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling	27
Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection	27
RAB1A haploinsufficiency phenocopies the 2p14–p15 microdeletion and is associated with impaired neuronal differentiation	27
A cardiovascular, craniofacial, and neurodevelopmental disorder caused by loss-of-function variants in the eIF3 complex component genes EIF3A and EIF3B	27
Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population	27
GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals	27
Landscapes of missense variant impact for human superoxide dismutase 1	27
Bi-allelic variants in FSD1L cause retinitis pigmentosa with or without neurological involvement	27
Implementing a training resource for large-scale genomic data analysis in the All of Us Researcher Workbench	26
Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders	26
An allelic-series rare-variant association test for candidate-gene discovery	26
eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?	26
Dissecting the high-resolution genetic architecture of complex phenotypes by accurately estimating gene-based conditional heritability	26
This month in The Journal	26
De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms	26
The utility of ultra-deep RNA sequencing in Mendelian disorder diagnostics	26
Response to Li and Hopper	26
Sensitivity of HiFi long-read genome sequencing for difficult-to-detect pathogenic variants when applied to real-world clinical laboratory samples	25
High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes	25
The dawn of interventional genetics	25
Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic	25
A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1	25
Genotype error due to low-coverage sequencing induces uncertainty in polygenic scoring	25
75 years of The American Journal of Human Genetics	25
Mind the gap: Characterizing bias due to population mismatch in two-sample Mendelian randomization	24
A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer	24
MetaGLIMPSE: Meta-imputation of low-coverage sequencing data for modern and ancient genomes	24
Genetics-informed precision treatment formulation in schizophrenia and bipolar disorder	24
A massively parallel assay accurately discriminates between functionally normal and abnormal variants in a hotspot domain of KCNH2	23
Frequencies of pharmacogenomic alleles across biogeographic groups in a large-scale biobank	23
A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease	23
ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence	23
Consequences of chromosome gain: A new view on trisomy syndromes	23
Bi-allelic MED16 variants cause a MEDopathy with intellectual disability, motor delay, and craniofacial, cardiac, and limb malformations	23
The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans	23
CAG repeat mosaicism is gene specific in spinocerebellar ataxias	23
Misattributed paternity discovery: A critique of medical organizations’ recommendations	23
Understanding changes in genetic literacy over time and in genetic research participants	22
A scalable framework for identifying allelic series from summary statistics	22
High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility	22

Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits	22
AncientProxy: A catalog of ancient proxies for modern genetic variants	22
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk	22
Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy	22
Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study	22
Toward clinical exomes in diagnostics and management of male infertility	21
Local genetic correlation via knockoffs reduces confounding due to cross-trait assortative mating	21
Bi-allelic variants in NDUFA5 cause a mitochondriopathy with complex I deficiency	21
An RNA-informed dosage sensitivity map reflects the intrinsic functional nature of genes	21
The 2023 Distinguished Speakers Symposium: The future of human genetics and genomics	21
2022 Victor A. McKusick Leadership Award	21
Opportunities and challenges of local ancestry in genetic association analyses	21
Leveraging drug perturbation to reveal genetic regulators of hepatic gene expression in African Americans	21
Implications of family history and polygenic risk scores for causation	21
This month in The Journal	20
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature	20
MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway	20
Response to Bassett et al.	20
Navigating data sharing in research	20
This month in The Journal	20
Will variants of uncertain significance still exist in 2030?	20
Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly	20
An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14	20
CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans	20
Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing	20
This month in The Journal	20
Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans	19
Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia	19
Data sharing in the PRIMED Consortium: Design, implementation, and recommendations for future policymaking	19
International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review	19
Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study	19
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome	19
Distinct explanations underlie gene-environment interactions in the UK Biobank	19
Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets	19
STIGMA: Single-cell tissue-specific gene prioritization using machine learning	19
Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes	19
Knockoff procedure improves susceptibility gene identifications in conditional transcriptome-wide association studies	19
A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes	19
Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program	18
KnockoffTrio: A knockoff framework for the identification of putative causal variants in genome-wide association studies with trio design	18
Fast, accurate local ancestry inference with FLARE	18
Exploring the noncoding genome with chromosomal structural rearrangements	18
Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder	18
Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications	18
Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets	18
Meta-analysis across six global biobanks identifies recessive coding associations with complex traits and diseases	18
GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy	18
Estimating gene conversion rates from population data using multi-individual identity by descent	18
Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes	18
An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome	18
When two plus four does not equal six: Combining computational and functional evidence to classify BRCA1 key domain missense substitutions	17
Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants	17
Closing the loop: Editors' feedback on the ASHG readership survey	17
Public preferences for the value and implementation of genomic newborn screening: Insights from two discrete choice experiments in Australia	17
High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma	17
Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range	17
Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression	17
FBXO22 deficiency defines a pleiotropic syndrome of growth restriction and multi-system anomalies associated with a unique epigenetic signature	17
Impact of genome build on RNA-seq interpretation and diagnostics	17
Leveraging local ancestry and cross-ancestry genetic architecture to improve genetic prediction of complex traits in admixed populations	17
Role of X chromosome and dosage-compensation mechanisms in complex trait genetics	17
First steps toward building natural history of diseases computationally: Lessons learned from the Noonan syndrome use case	17
Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts	17