Kaitlin E. Samocha

The paper identifies 253 autism-associated genes using rare variation from 62,429 individuals and finds pleiotropy across physiological systems and developmental disorders.

The paper identifies novel spliceosome-related genes and pseudogenes associated with rare diseases using variant analysis and prioritization methods.

The paper estimates mutation rates and variant effects using 700k exomes to identify genes with mutational hotspots and improve variant prioritization for genetic diagnostics.

The paper presents genetic and phenotypic data from 521 children with neurodevelopmental disorders in Kenya and South Africa, highlighting high genetic diagnosis rates linked to environmental risk factors.

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

The paper develops an automated tool for reanalyzing genomic data in rare disease cohorts, showing improved diagnostic yields through iterative reanalysis.

The paper investigates the role of rare inherited coding variants in developmental disorders by analyzing family and case/control data, finding significant burdens of damaging variants and estimating their population attributable risk.

This paper introduces GISMO and GISMO-mis metrics to quantify gene loss and missense variation across mammals, identifying essential genes and improving gene-disease associations.

The paper quantifies regional missense mutational intolerance using 730,947 exomes to identify constrained gene regions and improve variant interpretation.

This study investigates how common genetic variants contribute to risk for rare neurodevelopmental conditions and examines indirect genetic effects through parental non-transmitted alleles.

The paper quantifies the contribution of recessive coding variants to developmental disorders in diverse populations, identifying novel genes and highlighting challenges in interpreting missense variants.

The paper investigates whether common cis-regulatory variants modify the penetrance of rare damaging coding variants in neurodevelopmental disorders using transcriptome-wide association and cis-eQTL analysis.

This study estimates the impact of genetic risk factors on disease burden using disability-adjusted life years (DALYs) and finds that both common and rare variants significantly contribute to healthy life years lost.

This study identifies 114 genome-wide significant rare CNV-disease associations across 30 neurological disorders, revealing 38 novel triplosensitive genes and developing a model to predict dosage sensitivity.

The paper reports diagnostic outcomes from a large-scale genomic study of developmental disorders, identifying factors that influence diagnostic success.

The paper links reduced reproductive success to selective constraint on human genes, showing that damaging variants are associated with increased childlessness, particularly in males.

This paper introduces HMC, a high-resolution genetic constraint score for missense variants, improving variant prioritization and gene discovery for developmental disorders.

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

The paper analyzes X-linked coding variation in developmental disorders, finding similar rates in males and females and estimating pathogenicity of inherited variants.

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

The paper develops an expression-based annotation metric to improve rare variant interpretation by filtering false-positive loss-of-function variants and identifying pathogenic variants in highly expressed exons.

Short-read genome sequencing of 14,891 diverse genomes yields 433,371 structural variants (SVs) for gnomAD; loss-constrained genes also resist duplication, and clinical SV carrier rates are benchmarked.

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

The paper systematically studies uORF variants in 15,708 genomes, showing they are under strong negative selection and contribute to disease.

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

The paper integrates healthcare and research exome sequences to identify 28 novel developmental disorder-associated genes using a simulation-based statistical test.

The paper identifies 299 new genes associated with developmental disorders using exome data from 31,058 trios and finds many more likely remain undiscovered.

The paper identifies retrotransposition events in developmental disorders using exome sequencing data from the DDD study and shows their evolutionary constraints.

This study examines the contribution of protein-coding de novo mutations to schizophrenia risk using whole-exome sequencing data from parent-offspring trios, finding a modest but polygenic effect.