American Journal of Human Genetics

Article	Citations
This month in The Journal	513
2022 Curt Stern Award introduction: Heidi Rehm	471
This month in The Journal	450
Genetic determinants of IgG antibody response to COVID-19 vaccination	272
Best practices for improving alignment and variant calling on human sex chromosomes	153
This month in The Journal	147
Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt	146
Potential corporate uses of polygenic indexes: Starting a conversation about the associated ethics and policy issues	143
AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia	109
Genomes and epigenomes of matched normal and tumor breast tissue reveal diverse evolutionary trajectories and tumor-host interactions	97
Genetic control of non-coding RNAs in the human brain and their implications for complex traits	95
Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction	95
Mendelian randomization linking metabolites with enzymes reveals pathway regulation and therapeutic avenues	93
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease	92
Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program	91
Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability	88
Measuring disease likelihood in genomic ascertainment	82
The Electronic Medical Records and Genomics study: Design and analytic framework for assessing the impact of genome-informed risk assessments	78
“Choice of law” in precision medicine research	77
Fast and accurate Bayesian polygenic risk modeling with variational inference	76
Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA	71
Evaluating large language models on medical, lay-language, and self-reported descriptions of genetic conditions	70
Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the “omnigenic” sparse effector hypothesis of complex trait genetics	69
Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes	67
mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data	67

This Month in The Journal	65
Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples	64
shaPRS: Leveraging shared genetic effects across traits or ancestries improves accuracy of polygenic scores	63
Human leukocyte antigen variation is associated with cytomegalovirus serostatus in healthy individuals	63
Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus	63
Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants	62
Actionable genetic variants in 4,198 Scottish participants from the Orkney and Shetland founder populations and implementation of return of results	60
The impact of inversions across 33,924 families with rare disease from a national genome sequencing project	60
This month in The Journal	56
Improving polygenic risk prediction performance by integrating electronic health records through phenotype embedding	55
A spectrum of recessiveness among Mendelian disease variants in UK Biobank	54
2022 ASHG presidential address—One human race: Billions of genomes	54
Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags	53
Improved detection of aberrant splicing with FRASER 2.0 and the intron Jaccard index	52
Neurodevelopmental copy-number variants: A roadmap to improving outcomes by uniting patient advocates, researchers, and clinicians for collective impact	51
Sequence variants in HECTD1 result in a variable neurodevelopmental disorder	50
2022 Curt Stern Award: Advancing genomic medicine through collaboration and data sharing	50
This month in The Journal	49
2024 ASHG Scientific Achievement Award	48
A new annual feature of AJHG: All of Us Research Program year in review	47
Bi-allelic PRMT9 loss-of-function variants cause a syndromic form of intellectual disability	47
The ancestry and geographical origins of St Helena’s liberated Africans	46
SMN1 variants identified by false-positive SMA newborn screening tests: Therapeutic hurdles and functional and epidemiological solutions	45
A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3	45
Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts	45
Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders	45
Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4	45
The association of cigarette smoking with DNA methylation and gene expression in human tissue samples	44
Benchmarking Mendelian randomization methods for causal inference using genome-wide association study summary statistics	42
Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background	42
Unraveling the impact of VHL exon 2 mutations in erythrocytosis or von Hippel-Lindau disease identified RNA-binding proteins involved in VHL splicing	41
Addressing underrepresentation in genomics research through community engagement	41
To boldly go: Unpacking the NHGRI’s bold predictions for human genomics by 2030	41
Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis	40
Literature-based predictions of Mendelian disease therapies	40
Structural biology in variant interpretation: Perspectives and practices from two studies	40
SpliceVarDB: A comprehensive database of experimentally validated human splicing variants	40
Using the ancestral recombination graph to study the history of rare variants in founder populations	39
Transcriptome-wide association study of the plasma proteome reveals cis and trans regulatory mechanisms underlying complex traits	39
2023 ASHG presidential address—Reflecting on our 75 years: Acknowledging our past, embracing our present, and dreaming about our future	38
This month in The Journal	38
This month in The Journal	38
Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies	37
Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention	36
Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications	36
BRCA1-, BRCA2-, and PALB2-related Fanconi anemia: Scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes	36
Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy	36
Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models	35
A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens	35
Incorporating polygenic risk scores and social determinants of health across populations: Considerations and best practices in research	35

Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits	35
Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites	35
Newborn screening for type 1 diabetes using genome-based risk scores in the Early Check program	35
Extremely early genomic events and temporal order of esophageal squamous cell carcinogenesis: Longitudinal self-comparison of progressors and non-progressors	34
Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations	34
Exploring the omnigenic architecture of selected complex traits	34
Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa	34
The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function	33
Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity	33
Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common control subjects	33
This Month in The Journal	33
Demographic history and genetic variation of the Armenian population	33
PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects	33
Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications	33
Significance tests for R2 of out-of-sample prediction using polygenic scores	33
COMPADRE: Combined pedigree-aware distant relatedness estimation for improved pedigree reconstruction	32
2025 ASHG awards and addresses	32
Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome	32
Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia	31
Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1	31
Validation and context-dependent effects of a prostate cancer polygenic risk score in the All of Us Research Program	31
Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants	31
Liver single-nucleus multiome profiling reveals cell-type mechanisms for cardiometabolic traits	31
2022 William Allan Award introduction: Peter Donnelly	31
The ancestry and geographical origins of St Helena’s liberated Africans	31
Functional classification of platelet gene variants using CRISPR HDR in CD34+ cell-derived megakaryocytes	31
LiMA: Robust inference of molecular mediation from summary statistics	30
A powerful approach to identify replicable variants in genome-wide association studies	30
Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation	30
This month in The Journal	29
Dissecting the high-resolution genetic architecture of complex phenotypes by accurately estimating gene-based conditional heritability	29
Inherited HTT CAG repeat length does not have a major impact on Huntington disease duration	29
Implementing a training resource for large-scale genomic data analysis in the All of Us Researcher Workbench	29
Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies	29
Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders	29
Haplotype analysis reveals pleiotropic disease associations in the HLA region	28
RAB1A haploinsufficiency phenocopies the 2p14–p15 microdeletion and is associated with impaired neuronal differentiation	28
Investigating the potential of single-cell DNA methylation data to detect allele-specific methylation and imprinting	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
Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection	28
De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms	28
A cardiovascular, craniofacial, and neurodevelopmental disorder caused by loss-of-function variants in the eIF3 complex component genes EIF3A and EIF3B	27
GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals	27
eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?	27
Bi-allelic variants in FSD1L cause retinitis pigmentosa with or without neurological involvement	27
Landscapes of missense variant impact for human superoxide dismutase 1	27
The utility of ultra-deep RNA sequencing in Mendelian disorder diagnostics	27
Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population	27
De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling	27
An allelic-series rare-variant association test for candidate-gene discovery	26
The dawn of interventional genetics	26
Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders	26
Consequences of chromosome gain: A new view on trisomy syndromes	26
75 years of The American Journal of Human Genetics	26
Trio RNA sequencing in a cohort of medically complex children	26
Understanding changes in genetic literacy over time and in genetic research participants	26
Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds	26
Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study	25
Genotype error due to low-coverage sequencing induces uncertainty in polygenic scoring	25
A massively parallel assay accurately discriminates between functionally normal and abnormal variants in a hotspot domain of KCNH2	25
This month in The Journal	25
Response to Li and Hopper	25
High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes	25
A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1	25
A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer	25
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk	24
Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy	24
A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease	24
Bi-allelic MED16 variants cause a MEDopathy with intellectual disability, motor delay, and craniofacial, cardiac, and limb malformations	24
Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic	24
Misattributed paternity discovery: A critique of medical organizations’ recommendations	24
AncientProxy: A catalog of ancient proxies for modern genetic variants	24
Frequencies of pharmacogenomic alleles across biogeographic groups in a large-scale biobank	23
Sensitivity of HiFi long-read genome sequencing for difficult-to-detect pathogenic variants when applied to real-world clinical laboratory samples	23
The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans	23
Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits	23
High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility	23
CAG repeat mosaicism is gene specific in spinocerebellar ataxias	23
MetaGLIMPSE: Meta-imputation of low-coverage sequencing data for modern and ancient genomes	23

A scalable framework for identifying allelic series from summary statistics	23
Mind the gap: Characterizing bias due to population mismatch in two-sample Mendelian randomization	23
ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence	23
Bi-allelic variants in NDUFA5 cause a mitochondriopathy with complex I deficiency	22
Local genetic correlation via knockoffs reduces confounding due to cross-trait assortative mating	22
This month in The Journal	22
Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing	22
The 2023 Distinguished Speakers Symposium: The future of human genetics and genomics	22
Genetics-informed precision treatment formulation in schizophrenia and bipolar disorder	22
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature	22
This month in The Journal	22
2022 Victor A. McKusick Leadership Award	21
An RNA-informed dosage sensitivity map reflects the intrinsic functional nature of genes	21
MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway	21
Toward clinical exomes in diagnostics and management of male infertility	21
CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans	21
Will variants of uncertain significance still exist in 2030?	21
An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14	21
Implications of family history and polygenic risk scores for causation	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
Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications	20
STIGMA: Single-cell tissue-specific gene prioritization using machine learning	20
Response to Wyckelsma et al.: Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation	20
Response to Bassett et al.	20
Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets	20
Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets	20
An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome	20
This month in The Journal	20
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome	20
Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans	19
Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes	19
Data sharing in the PRIMED Consortium: Design, implementation, and recommendations for future policymaking	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
Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia	19
KnockoffTrio: A knockoff framework for the identification of putative causal variants in genome-wide association studies with trio design	19
GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy	19
Knockoff procedure improves susceptibility gene identifications in conditional transcriptome-wide association studies	19
Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study	19
Estimating gene conversion rates from population data using multi-individual identity by descent	19
Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program	19
Distinct explanations underlie gene-environment interactions in the UK Biobank	18
Neither cardiac mitochondrial DNA variation nor copy number contribute to congenital heart disease risk	18
Exploring the noncoding genome with chromosomal structural rearrangements	18
Closing the loop: Editors' feedback on the ASHG readership survey	18
Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy	18
Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes	18
International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review	18
Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression	18
De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement	18
Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder	18
Fast, accurate local ancestry inference with FLARE	18
First steps toward building natural history of diseases computationally: Lessons learned from the Noonan syndrome use case	18
Transcriptome-wide outlier approach identifies individuals with minor spliceopathies	18
Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease	17
Comprehensive evaluation and efficient classification of BRCA1 RING domain missense substitutions	17
Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range	17
Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders	17
The Clinical Pharmacogenetics Implementation Consortium’s consensus-based framework for assigning allele function	17
Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis	17
Leveraging local ancestry and cross-ancestry genetic architecture to improve genetic prediction of complex traits in admixed populations	17
Addressing the challenges of polygenic scores in human genetic research	17
Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank	17
Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing	17
When two plus four does not equal six: Combining computational and functional evidence to classify BRCA1 key domain missense substitutions	17