David H. Ledbetter
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View article: X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height
X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height Open
Many human phenotypic traits vary between the sexes, including adult height for which males are, on average, 13 cm taller than females. The biological mechanisms for this sexual dimorphism are not entirely understood. One hypothesis to exp…
View article: P188: Clinical and personal utility of population screening for neurodevelopmental psychiatric copy number variants and sex chromosome aneuploidies in 580 adults
P188: Clinical and personal utility of population screening for neurodevelopmental psychiatric copy number variants and sex chromosome aneuploidies in 580 adults Open
View article: A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk
A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk Open
A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypo…
View article: O22: Integrating genomic medicine into healthcare: Experience disclosing >5,000 clinically relevant results within the Geisinger MyCode Community Health Initiative
O22: Integrating genomic medicine into healthcare: Experience disclosing >5,000 clinically relevant results within the Geisinger MyCode Community Health Initiative Open
The integration of genomic medicine into mainstream healthcare has long been awaited and is a necessary step towards realizing the promise of precision health. With decreasing sequencing costs and expanding knowledge of genetics and health…
View article: Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases
Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases Open
View article: A novel application of spectrograms with machine learning can detect patient ventilator dyssynchrony
A novel application of spectrograms with machine learning can detect patient ventilator dyssynchrony Open
Patients in intensive care units are frequently supported by mechanical ventilation. There is increasing awareness of patient-ventilator dyssynchrony (PVD), a mismatch between patient respiratory effort and assistance provided by the venti…
View article: Rare coding variants in CHRNB2 reduce the likelihood of smoking
Rare coding variants in CHRNB2 reduce the likelihood of smoking Open
View article: Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines
Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines Open
Importance Exome sequencing is a first-tier diagnostic test for individuals with neurodevelopmental disorders, including intellectual disability/developmental delay and autism spectrum disorder; however, this recommendation does not includ…
View article: Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism
Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism Open
Importance An increased risk of venous thromboembolism (VTE) has been reported in men with an additional sex chromosome. The association between other sex chromosome aneuploidies and VTE is not well characterized. Objective To determine if…
View article: Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population
Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population Open
Collectively, rare single-gene variants and CNVs were found in >1% of individuals in a large health care system population and play an important contributory role in mental health disorders. Diagnostic genetic testing for pathogenic varian…
View article: Phenotypic shift in copy number variants: Evidence in 16p11.2 duplication syndrome
Phenotypic shift in copy number variants: Evidence in 16p11.2 duplication syndrome Open
View article: Population-scale analysis of common and rare genetic variation associated with hearing loss in adults
Population-scale analysis of common and rare genetic variation associated with hearing loss in adults Open
View article: Frequency of truncating FLCN variants and Birt-Hogg-Dubé–associated phenotypes in a health care system population
Frequency of truncating FLCN variants and Birt-Hogg-Dubé–associated phenotypes in a health care system population Open
In this health care population, the frequency of P/LP truncating FLCN variants is 60 times higher than the previously reported prevalence. Although most variant-positive individuals had BHD-related phenotypes, a minority were previously cl…
View article: Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology
Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology Open
Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to dat…
View article: Frequency of <i>FLCN</i> Loss of Function Variants and Birt-Hogg-Dubé-Associated Phenotypes in a Healthcare System Population
Frequency of <i>FLCN</i> Loss of Function Variants and Birt-Hogg-Dubé-Associated Phenotypes in a Healthcare System Population Open
Purpose Current penetrance estimates of Birt-Hogg-Dubé (BHD)-associated cutaneous, pulmonary, and renal manifestations are based on clinically ascertained families. In a healthcare system population, we used a genetics-first approach to es…
View article: Medical manifestations and health care utilization among adult MyCode participants with neurodevelopmental psychiatric copy number variants
Medical manifestations and health care utilization among adult MyCode participants with neurodevelopmental psychiatric copy number variants Open
View article: Correction to: Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants
Correction to: Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants Open
View article: Recontacting registry participants with genetic updates through GenomeConnect, the ClinGen patient registry
Recontacting registry participants with genetic updates through GenomeConnect, the ClinGen patient registry Open
View article: Population Genomic Screening for Genetic Etiologies of Neurodevelopmental/Psychiatric Disorders Demonstrates Personal Utility and Positive Participant Responses
Population Genomic Screening for Genetic Etiologies of Neurodevelopmental/Psychiatric Disorders Demonstrates Personal Utility and Positive Participant Responses Open
Genomic variants that cause neurodevelopmental/psychiatric disorders (NPD) are relatively prevalent and highly penetrant. This study aimed to understand adults’ immediate responses to receiving NPD-related results to inform inclusion in po…
View article: Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy
Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy Open
Among 2 cohorts of patients with cerebral palsy who underwent exome sequencing, the prevalence of pathogenic and likely pathogenic variants was 32.7% in a cohort that predominantly consisted of pediatric patients and 10.5% in a cohort that…
View article: Diagnostic genetic testing for neurodevelopmental psychiatric disorders: closing the gap between recommendation and clinical implementation
Diagnostic genetic testing for neurodevelopmental psychiatric disorders: closing the gap between recommendation and clinical implementation Open
View article: Electronic health record analysis identifies kidney disease as the leading risk factor for hospitalization in confirmed COVID-19 patients
Electronic health record analysis identifies kidney disease as the leading risk factor for hospitalization in confirmed COVID-19 patients Open
Background Empirical data on conditions that increase risk of coronavirus disease 2019 (COVID-19) progression are needed to identify high risk individuals. We performed a comprehensive quantitative assessment of pre-existing clinical pheno…
View article: ClinGen — The Clinical Genome Resource
ClinGen — The Clinical Genome Resource Open
On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given …
View article: Response to Buxbaum et al.
Response to Buxbaum et al. Open
View article: Characterizing Genetic Variants for Clinical Action
Characterizing Genetic Variants for Clinical Action Open
Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatm…
View article: Exome sequencing and characterization of 49,960 individuals in the UK Biobank
Exome sequencing and characterization of 49,960 individuals in the UK Biobank Open
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world 1 . Here we describe the release of exome-sequence data for the first …
View article: Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders
Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders Open
View article: Improving Recurrent Neural Network Responsiveness to Acute Clinical\n Events
Improving Recurrent Neural Network Responsiveness to Acute Clinical\n Events Open
Predictive models in acute care settings must be able to immediately\nrecognize precipitous changes in a patient's status when presented with data\nreflecting such changes. Recurrent neural networks (RNNs) have become common\nfor training …
View article: Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population
Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population Open
This study informs critical factors central to the development of population-based genomic screening programs and supports the inclusion of NPD in future designs to promote equitable access to clinically useful genomic information.
View article: Clinical outcomes of a genomic screening program for actionable genetic conditions
Clinical outcomes of a genomic screening program for actionable genetic conditions Open