Daniel G. MacArthur
YOU?
Author Swipe
View article: GREGoR: accelerating genomics for rare diseases
GREGoR: accelerating genomics for rare diseases Open
View article: Undiagnosed G6PD Deficiency in Black and Asian Individuals Is Prevalent and Contributes to Health Inequalities in Type 2 Diabetes Diagnosis and Complications
Undiagnosed G6PD Deficiency in Black and Asian Individuals Is Prevalent and Contributes to Health Inequalities in Type 2 Diabetes Diagnosis and Complications Open
OBJECTIVE Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents silently and is not routinely screened. It is associated with markedly lower HbA1c for the prevailing glucose levels. Since HbA1c is internationally recommended to diag…
View article: XBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries
XBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries Open
View article: Genetic regulation of cell type–specific chromatin accessibility shapes immune function and disease risk
Genetic regulation of cell type–specific chromatin accessibility shapes immune function and disease risk Open
Understanding how genetic variation influences gene regulation at the single-cell level is crucial for elucidating the mechanisms underlying complex diseases. However, limited large-scale single-cell multi-omics data have constrained our u…
View article: Single-cell genetics identifies cell type-specific causal mechanisms in complex traits and diseases
Single-cell genetics identifies cell type-specific causal mechanisms in complex traits and diseases Open
Genome-wide association studies (GWAS) have been instrumental in uncovering the genetic basis of complex traits. When integrated with expression quantitative trait loci (eQTL) mapping, they can elucidate how risk loci influence traits thro…
View article: Endothelial Colony-Forming Cell Transcriptomic Profiling in CT-defined Coronary Artery Disease from the BioHEART-CT Study Implicate CCBE1 in Mitochondrial Dysfunction-associated Atherosclerosis
Endothelial Colony-Forming Cell Transcriptomic Profiling in CT-defined Coronary Artery Disease from the BioHEART-CT Study Implicate CCBE1 in Mitochondrial Dysfunction-associated Atherosclerosis Open
Background Endothelial dysfunction is an early contributor to atherosclerosis. This study combined CT imaging of coronary artery disease (CAD) and patient-dervied endothelial colony-forming cells (ECFCs) transcriptional profiling to invest…
View article: Biallelic variants in the non-coding RNA gene <i>RNU4-2</i> cause a recessive neurodevelopmental syndrome with distinct white matter changes
Biallelic variants in the non-coding RNA gene <i>RNU4-2</i> cause a recessive neurodevelopmental syndrome with distinct white matter changes Open
Genetic variants in RNU4-2 , which encodes U4, a key non-coding small nuclear RNA (snRNA) component of the major spliceosome, were recently shown to cause a prevalent neurodevelopmental disorder (NDD) called ReNU syndrome. These variants, …
View article: Axenfeld-Rieger syndrome associated with a megabase-scale inversion separating<i>PITX2</i>from a conserved enhancer locus
Axenfeld-Rieger syndrome associated with a megabase-scale inversion separating<i>PITX2</i>from a conserved enhancer locus Open
Axenfeld–Rieger Syndrome (ARS) is an autosomal dominant condition with both ocular and non-ocular manifestations. ARS is primarily caused by coding variants at the PITX2 or FOXC1 loci, yet many cases still remain undiagnosed. Here we used …
View article: Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity
Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity Open
Genes and Health (G&H) is a biomedical study of adult British-Pakistani and -Bangladeshi research volunteers enriched for autozygosity. We performed whole exome sequencing in 44,028 G&H participants, establishing the largest publicly avail…
View article: Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts
Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts Open
Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necessary to ensure scalability, adoption and…
View article: Saturation genome editing of<i>RNU4-2</i>reveals distinct dominant and recessive neurodevelopmental disorders
Saturation genome editing of<i>RNU4-2</i>reveals distinct dominant and recessive neurodevelopmental disorders Open
Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thousands of individuals worldwide 1,2 . RNU…
View article: Characterization of severe COL6-related dystrophy due to the recurrent variant <i>COL6A1</i> c.930+189C&gt;T
Characterization of severe COL6-related dystrophy due to the recurrent variant <i>COL6A1</i> c.930+189C>T Open
Collagen VI-related dystrophies manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterized by progressive muscle weakness, joi…
View article: Impact of rare and common genetic variation on cell type-specific gene expression in human blood
Impact of rare and common genetic variation on cell type-specific gene expression in human blood Open
Understanding the genetic basis of gene expression can shed light on the regulatory mechanisms underlying complex traits and diseases. Single cell-resolved measures of RNA levels and single-cell expression quantitative trait loci (sc-eQTLs…
View article: The Evidence Aggregator: AI reasoning applied to rare disease diagnostics
The Evidence Aggregator: AI reasoning applied to rare disease diagnostics Open
Variant assessment of rare disease diagnostics depends on using domain knowledge in the time- consuming process of retrieving, reviewing, and synthesizing clinical and technical information. To address these challenges, we developed the Ev…
View article: Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol
Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol Open
View article: Pitfalls in performing genome-wide association studies on ratio traits
Pitfalls in performing genome-wide association studies on ratio traits Open
Genome-wide association studies (GWASs) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implici…
View article: Investigating misclassification of type 1 diabetes in a population-based cohort of British Pakistanis and Bangladeshis using polygenic risk scores
Investigating misclassification of type 1 diabetes in a population-based cohort of British Pakistanis and Bangladeshis using polygenic risk scores Open
View article: P647: Improving rare disease diagnosis: Performance of an automated pipeline for genomic reanalysis
P647: Improving rare disease diagnosis: Performance of an automated pipeline for genomic reanalysis Open
View article: Genetic basis of early onset and progression of type 2 diabetes in South Asians
Genetic basis of early onset and progression of type 2 diabetes in South Asians Open
South Asians develop type 2 diabetes (T2D) early in life and often with normal body mass index (BMI). However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups. We used recently…
View article: Polymorphic tandem repeats influence cell type-specific gene expression across the human immune landscape
Polymorphic tandem repeats influence cell type-specific gene expression across the human immune landscape Open
Tandem repeats (TRs) - highly polymorphic, repetitive sequences dispersed across the human genome - are crucial regulators of gene expression and diverse biological processes, but have remained underexplored relative to other classes of ge…
View article: Genetic architecture of routinely acquired blood tests in a British South Asian cohort
Genetic architecture of routinely acquired blood tests in a British South Asian cohort Open
Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Health…
View article: A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders
A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders Open
View article: Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database
Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database Open
Incomplete penetrance, or absence of disease phenotype in an individual with a disease-associated variant, is a major challenge in variant interpretation. Studying individuals with apparent incomplete penetrance can shed light on underlyin…
View article: Efficient and accurate mixed model association tool for single-cell eQTL analysis
Efficient and accurate mixed model association tool for single-cell eQTL analysis Open
Understanding the genetic basis of gene expression can help us understand the molecular underpinnings of human traits and disease. Expression quantitative trait locus (eQTL) mapping can help in studying this relationship but have been show…
View article: The landscape of regional missense mutational intolerance quantified from 125,748 exomes
The landscape of regional missense mutational intolerance quantified from 125,748 exomes Open
Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within gen…
View article: <i>De novo</i>variants in the non-coding spliceosomal snRNA gene<i>RNU4-2</i>are a frequent cause of syndromic neurodevelopmental disorders
<i>De novo</i>variants in the non-coding spliceosomal snRNA gene<i>RNU4-2</i>are a frequent cause of syndromic neurodevelopmental disorders Open
Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Increasingly, large genome-sequenced cohorts are improving our ability to disco…
View article: Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease Open
View article: The recurrent deep intronic pseudoexon-inducing variant<i>COL6A1</i>c.930+189C>T results in a consistently severe phenotype of COL6-related dystrophy: Towards clinical trial readiness for splice-modulating therapy
The recurrent deep intronic pseudoexon-inducing variant<i>COL6A1</i>c.930+189C>T results in a consistently severe phenotype of COL6-related dystrophy: Towards clinical trial readiness for splice-modulating therapy Open
Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterised by progressive muscle we…
View article: Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders
Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders Open
Purpose To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). Methods We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genet…
View article: Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy
Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy Open
In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleter…