American Journal of Human Genetics

Article	Citations
Fast two-stage phasing of large-scale sequence data	334
30 years of repeat expansion disorders: What have we learned and what are the remaining challenges?	228
Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria	194
Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort	184
Combining evidence from Mendelian randomization and colocalization: Review and comparison of approaches	181
Constrained maximum likelihood-based Mendelian randomization robust to both correlated and uncorrelated pleiotropic effects	173
Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care	155
15 years of GWAS discovery: Realizing the promise	150
Optical genome mapping enables constitutional chromosomal aberration detection	138
Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial	137
Topologically associating domain boundaries that are stable across diverse cell types are evolutionarily constrained and enriched for heritability	133
Targeted long-read sequencing identifies missing disease-causing variation	123
An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm	119
Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping	106
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility	90
A unified framework for cross-population trait prediction by leveraging the genetic correlation of polygenic traits	89
Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa	86
Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies	82
Estimation of non-additive genetic variance in human complex traits from a large sample of unrelated individuals	79
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk	78
A dyadic approach to the delineation of diagnostic entities in clinical genomics	77
Probabilistic colocalization of genetic variants from complex and molecular traits: promise and limitations	76
An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14	76
Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype	76
A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases	75

Improved pathogenicity prediction for rare human missense variants	75
The omnigenic model and polygenic prediction of complex traits	74
Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup	73
Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals	73
Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years	71
Cancer PRSweb: An Online Repository with Polygenic Risk Scores for Major Cancer Traits and Their Evaluation in Two Independent Biobanks	70
Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice	69
De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families	65
A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants	65
Using genetic association data to guide drug discovery and development: Review of methods and applications	65
Systematic comparison of family history and polygenic risk across 24 common diseases	65
Massively parallel characterization of CYP2C9 variant enzyme activity and abundance	64
Genetic control of the human brain proteome	64
Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia	64
Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation	61
Closing the gap: Systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN	59
Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice	58
Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations	58
A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos	57
Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans	56
Variant Classification Concordance using the ACMG-AMP Variant Interpretation Guidelines across Nine Genomic Implementation Research Studies	55
SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females	54
Opportunities and challenges for the computational interpretation of rare variation in clinically important genes	51
Leveraging phenotypic variability to identify genetic interactions in human phenotypes	51
High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population	49
Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies	49
Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome	48
Spectrum of splicing variants in disease genes and the ability of RNA analysis to reduce uncertainty in clinical interpretation	48
Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study	48
De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment	47
Automated AI labeling of optic nerve head enables insights into cross-ancestry glaucoma risk and genetic discovery in >280,000 images from UKB and CLSA	47
Progressive myoclonus epilepsies—Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes	46
Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution	46
Robust genetic nurture effects on education: A systematic review and meta-analysis based on 38,654 families across 8 cohorts	46
SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling	45
Familial long-read sequencing increases yield of de novo mutations	45
The CGG repeat expansion in RILPL1 is associated with oculopharyngodistal myopathy type 4	45
Exome variant discrepancies due to reference-genome differences	44
The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects	43
Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction	43
Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms	43
Large-scale machine-learning-based phenotyping significantly improves genomic discovery for optic nerve head morphology	43
The individual and global impact of copy-number variants on complex human traits	42
Multiplexed Functional Assessment of Genetic Variants in CARD11	42
Brain-trait-associated variants impact cell-type-specific gene regulation during neurogenesis	41
Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization	41
Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome	41
Genetic modifiers of Huntington disease differentially influence motor and cognitive domains	41
Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts	41
Analysis of missense variants in the human genome reveals widespread gene-specific clustering and improves prediction of pathogenicity	41

Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2	41
Rare genetic variants in genes and loci linked to dominant monogenic developmental disorders cause milder related phenotypes in the general population	41
Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature	41
Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals	40
Common haplotypes at the CFH locus and low-frequency variants in CFHR2 and CFHR5 associate with systemic FHR concentrations and age-related macular degeneration	40
Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk	40
Redefining tissue specificity of genetic regulation of gene expression in the presence of allelic heterogeneity	39
Anatomy of DNA methylation signatures: Emerging insights and applications	39
BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms	39
Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia	39
Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits	38
Negative selection on complex traits limits phenotype prediction accuracy between populations	38
Addressing underrepresentation in genomics research through community engagement	38
Strong functional data for pathogenicity or neutrality classify BRCA2 DNA-binding-domain variants of uncertain significance	38
Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study	37
Shifting landscapes of human MTHFR missense-variant effects	36
Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction	36
Multi-trait transcriptome-wide association studies with probabilistic Mendelian randomization	36
Germline and Mosaic Variants in PRKACA and PRKACB Cause a Multiple Congenital Malformation Syndrome	36
H3K27ac HiChIP in prostate cell lines identifies risk genes for prostate cancer susceptibility	36
TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data	36
Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation	35
Interpretable prioritization of splice variants in diagnostic next-generation sequencing	35
SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype	35
Establishing risk of vision loss in Leber hereditary optic neuropathy	35
Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-p.Gly2019Ser-associated gene expression	33
Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations	33
Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss	33
Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort	33
A catalog of GWAS fine-mapping efforts in autoimmune disease	33
Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model	33
Evolving use of ancestry, ethnicity, and race in genetics research—A survey spanning seven decades	33
Personalized genetic counseling for Stargardt disease: Offspring risk estimates based on variant severity	32
Genetic effects on liver chromatin accessibility identify disease regulatory variants	32
Pervasive cis effects of variation in copy number of large tandem repeats on local DNA methylation and gene expression	32
Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis	31
On the reproductive capabilities of aneuploid human preimplantation embryos	31
Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations	31
PLEIO: a method to map and interpret pleiotropic loci with GWAS summary statistics	31
Germline MBD4 deficiency causes a multi-tumor predisposition syndrome	31
Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations	31
StrVCTVRE: A supervised learning method to predict the pathogenicity of human genome structural variants	31
Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities	30
The construction of cross-population polygenic risk scores using transfer learning	30
An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14	30
Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease	29
High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency	29
Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm	29
Efficient mixed model approach for large-scale genome-wide association studies of ordinal categorical phenotypes	29
A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl−/H+-Exchanger, Causes Early-Onset Neurodegeneration	29
Analysis of Trans-Ancestral SLE Risk Loci Identifies Unique Biologic Networks and Drug Targets in African and European Ancestries	29
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores	28
Failure to recombine is a common feature of human oogenesis	28
Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures	28
Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders	28
A Multi-omic Integrative Scheme Characterizes Tissues of Action at Loci Associated with Type 2 Diabetes	28
Identifying digenic disease genes via machine learning in the Undiagnosed Diseases Network	28
Identification of discriminative gene-level and protein-level features associated with pathogenic gain-of-function and loss-of-function variants	28
TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila	27
Quantifying the contribution of dominance deviation effects to complex trait variation in biobank-scale data	27
Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy	27
Genetic overlap and causality between blood metabolites and migraine	27
A spectrum of recessiveness among Mendelian disease variants in UK Biobank	27
The genetic architecture of pediatric cardiomyopathy	27
Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies	27
Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program	27
The genomics workforce must become more diverse: a strategic imperative	26
THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder	26
eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?	26
Germline predisposition to pediatric Ewing sarcoma is characterized by inherited pathogenic variants in DNA damage repair genes	26
Genotype first: Clinical genomics research through a reverse phenotyping approach	26
Association of structural variation with cardiometabolic traits in Finns	26
Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene	25
Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction	25
Longer CAG repeat length is associated with shorter survival after disease onset in Huntington disease	25
Bi-allelic variants in DNHD1 cause flagellar axoneme defects and asthenoteratozoospermia in humans and mice	25
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids	24
Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites	24
Rare coding variants in 35 genes associate with circulating lipid levels—A multi-ancestry analysis of 170,000 exomes	24
Probabilistic Estimation of Identity by Descent Segment Endpoints and Detection of Recent Selection	24

A transchromosomic rat model with human chromosome 21 shows robust Down syndrome features	23
Machine learning-based reclassification of germline variants of unknown significance: The RENOVO algorithm	23
Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy	23
Beyond the exome: What’s next in diagnostic testing for Mendelian conditions	23
VPS4A Mutations in Humans Cause Syndromic Congenital Dyserythropoietic Anemia due to Cytokinesis and Trafficking Defects	23
NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism	23
Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease	23
De novo and bi-allelic variants in AP1G1 cause neurodevelopmental disorder with developmental delay, intellectual disability, and epilepsy	22
Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome	22
Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism	22
Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome	22
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease	22
Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry	22
Meta-imputation: An efficient method to combine genotype data after imputation with multiple reference panels	21
De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy	21
DAAM2 Variants Cause Nephrotic Syndrome via Actin Dysregulation	21
Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders	21
Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome	21
Mutations in TP73 cause impaired mucociliary clearance and lissencephaly	21
Analyzing and reconciling colocalization and transcriptome-wide association studies from the perspective of inferential reproducibility	21
Recessive, Deleterious Variants in SMG8 Expand the Role of Nonsense-Mediated Decay in Developmental Disorders in Humans	21
Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing	21
Host genetic effects in pneumonia	21
The genomic signatures of natural selection in admixed human populations	21
A multi-dimensional integrative scoring framework for predicting functional variants in the human genome	21
Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism	21
Robust multivariable Mendelian randomization based on constrained maximum likelihood	21
GWAS of longitudinal trajectories at biobank scale	21
A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer	21
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk	21
Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia	20
Care4Rare Canada: Outcomes from a decade of network science for rare disease gene discovery	20
Haploinsufficiency of the Sin3/HDAC corepressor complex member SIN3B causes a syndromic intellectual disability/autism spectrum disorder	20
Significance tests for R2 of out-of-sample prediction using polygenic scores	20
ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model	20
Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?	20
Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders	20
De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement	20
COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay	20
Inferring population structure in biobank-scale genomic data	19
Accounting for age of onset and family history improves power in genome-wide association studies	19
A calibrated functional patch-clamp assay to enhance clinical variant interpretation in KCNH2-related long QT syndrome	19
Genome-wide association study reveals an association between the HLA-DPB1∗02:01:02 allele and wheat-dependent exercise-induced anaphylaxis	19
An epigenome-wide view of osteoarthritis in primary tissues	19
Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare	19
Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach	19
Nonsense-mediated decay is highly stable across individuals and tissues	19
Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome	18
A recurrent de novo splice site variant involving DNM1 exon 10a causes developmental and epileptic encephalopathy through a dominant-negative mechanism	18
Fast estimation of genetic correlation for biobank-scale data	18
Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program	18
Tissue- and cell-type-specific molecular and functional signatures of 16p11.2 reciprocal genomic disorder across mouse brain and human neuronal models	18
Digital health-enabled genomics: Opportunities and challenges	18