Kashyap Amratlal Patel

Polygenic Background Contributes to GCK-MODY Clinical Presentation and Glycaemic Variability

This study shows that polygenic risk scores for diabetes traits are associated with higher HbA1c and increased diabetes diagnosis risk in GCK-MODY carriers, highlighting the interaction between monogenic and polygenic factors.

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations

This study uses whole-genome sequencing in 672,976 individuals to show rare and common variants converge in genetic associations for anthropometric traits, with ultra-rare variants explaining less than 10% of heritability.

Federated cross-biobank conditional analysis identifies LDL-C lowering effects of DNAJC13 haploinsufficiency and LDLR regulation

The paper uses a federated approach to conditionally analyze genetic variants across biobanks, identifying LDL-C lowering effects of DNAJC13 haploinsufficiency and LDLR regulation.

The minor spliceosome is a master immune regulator

The paper identifies biallelic variants in RNU6ATAC and RNU4ATAC as causes of early-onset autoimmune diabetes and immune dysregulation, showing the minor spliceosome's role in immune regulation.

Common Genetic Variants Modify Disease Risk and Clinical Presentation in Monogenic Diabetes

The paper shows that common genetic variants influence disease risk and severity in monogenic diabetes, modifying clinical outcomes in individuals with pathogenic variants.

NEUROD1 and PDX1 are low penetrance causes of MODY while rare variants in APPL1 and WFS1 are not associated with MODY

The paper assesses the genetic evidence for NEUROD1, PDX1, APPL1, and WFS1 in MODY, finding that only NEUROD1 and PDX1 variants are enriched, while APPL1 and WFS1 are not.

Mitochondrial heterogeneity disrupts osteoclast differentiation and bone resorption by impairing respiratory complex I

This study shows mitochondrial heteroplasmy impairs osteoclast differentiation and bone resorption by disrupting respiratory complex I and autophagy, and identifies spermidine as a potential therapeutic.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling

The paper identifies rare genetic variants associated with birth weight, highlighting genes involved in adipose tissue regulation, placental function, and insulin-like growth factor signaling.

Whole genome association testing in 333,100 individuals across three biobanks identifies rare non-coding single variant and genomic aggregate associations with height

Whole genome sequencing analysis identifies rare, large-effect non-coding variants and regions associated with circulating protein levels

The paper uses whole-genome sequencing data from UK Biobank participants to identify rare non-coding variants and regions associated with circulating protein levels.

Large-scale blood mitochondrial genome-wide study provides novel insights into mitochondrial disease-related traits

This study uses whole-genome sequencing to identify mitochondrial DNA variants associated with mitochondrial disease traits in a large population, finding novel associations and lower penetrance in unselected individuals.

Defining the nuclear genetic architecture of a common maternally inherited mitochondrial disorder

This paper identifies nuclear genetic factors modifying the clinical phenotype of m.3243A>G mitochondrial disease using genetic linkage analysis across 76 pedigrees.

A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1

The paper identifies non-coding mutations in a regulatory element of HK1 that lead to inappropriate expression in pancreatic beta-cells and cause congenital hyperinsulinism.

The penetrance of age-related monogenic disease depends on ascertainment context

The paper estimates penetrance of monogenic diabetes variants across different ascertainment contexts, finding age-related variability for HNF1A/HNF4A variants but consistent penetrance for GCK variants.

Genomic insights into the mechanism of NK3R antagonists for treatment of menopausal vasomotor symptoms

This paper identifies a genetic association between NK3R (TACR3) and menopausal vasomotor symptoms (VMS) using GWAS, while finding no link between rare NK3R variants and VMS despite the efficacy of NK3R antagonists.

SavvyCNV: genome-wide CNV calling from off-target reads

SavvyCNV calls genome-wide CNVs using off-target reads from exome and targeted sequencing, outperforming existing tools and detecting clinically relevant CNVs previously missed.

All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes

The paper examines how different glucose thresholds for gestational diabetes identify women with higher genetic risk for type 2 diabetes using genetic scores.

Assessing the pathogenicity, penetrance and expressivity of putative disease-causing variants in a population setting

This study uses UK Biobank data to assess the penetrance and pathogenicity of rare variants, finding reduced penetrance and variable expressivity for some clinically relevant variants.

Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance

This study identifies heterozygous RFX6 protein truncating variants as a cause of MODY with reduced penetrance, using genetic analysis and cohort comparisons.