David Curtis

Rare coding variation implicates thirteen genes in bipolar disorder across 232,536 individuals from global populations

Analysis of Rare Coding Variation Identifies New Genetic Contributors to Schizophrenia

Ultra-rare damaging coding variants in 87,959 schizophrenia cases and 150,587 controls implicate 40 genes (16 exome-wide, 24 at 5% FDR), half overlapping autism, developmental delay or bipolar genes.

Sequence effects on mutation frequencies investigated in whole-genome sequenced UK Biobank participants

The paper analyzes mutation frequencies in UK Biobank whole-genome sequences, finding that AC25 variants closely match de novo mutations and are influenced by DNA context and transcriptional processes.

Analysis of rare coding variants in 470,000 UK Biobank participants reveals genetic associations with childhood asthma predisposition

The paper analyzes rare coding variants in 470,000 UK Biobank participants and identifies genetic associations with childhood asthma predisposition, finding significant effects in FLG, IL33, and PRKCQ.

Analysis of rare coding variants in 470,000 exome-sequenced subjects characterises contributions to risk of type 2 diabetes

The paper analyzes rare coding variants in 470,000 exome-sequenced individuals to identify T2D-associated genes and characterize variant effects, finding no novel genes but confirming significant effects of specific variants in known genes.

Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease

This study evaluates AlphaMissense's ability to identify variants affecting disease susceptibility across 18 genes, comparing it to 43 other annotation methods.

Weighted burden analysis of rare coding variants in 470,000 exome-sequenced UK Biobank subject characterises effects on hyperlipidaemia risk

The paper extends a previous study by analyzing 270,000 additional UK Biobank exomes, confirming six genes' association with hyperlipidaemia risk and identifying protective and risk-increasing variant effects.

Using brain cell-type-specific protein interactomes to interpret genetic data in schizophrenia

The paper uses brain cell-type-specific protein interactomes to interpret genetic data in schizophrenia and identifies enriched networks and genes associated with the disease.

Analysis of rare variants in 470,000 exome-sequenced UK Biobank participants implicates novel genes affecting risk of hypertension

The paper analyzes rare variants in 470,000 UK Biobank participants to identify genes affecting hypertension risk, finding several exome-wide significant genes.

Study of association of migraine susceptibility genes with common migraine in 200,000 exome-sequenced UK Biobank participants

This study investigates the association of ten genes linked to migraine in rare syndromes with common migraine in 200,000 UK Biobank participants and finds no significant associations.

Clinical features of UK Biobank subjects carrying protein truncating variants in genes implicated in schizophrenia pathogenesis

The paper examines UK Biobank participants with protein truncating variants in schizophrenia-associated genes, finding limited psychiatric symptoms despite increased risk.

Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia

Exomes of 24,248 schizophrenia cases and 97,322 controls implicate ultra-rare damaging variants in 10 genes, including GRIN2A and GRIA3, with odds ratios of 3 to 50.

Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

This study identifies sex-dependent genetic risk loci shared and specific to mood and psychotic disorders using genome-wide interaction analysis.

Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

Meta-analysis of 41,917 European-ancestry bipolar disorder cases versus 371,549 controls yields 64 risk loci (33 novel), neuronal and synaptic gene enrichment, and 15 eQTL-prioritized genes.

Weighted burden analysis in 200 000 exome-sequenced UK Biobank subjects characterises effects of rare genetic variants on BMI

The paper uses weighted burden analysis on exome data from 199,807 UK Biobank subjects to identify rare variants associated with BMI, finding significant effects for MC4R and PCSK1.

Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia

The paper reports exome sequencing findings in bipolar disorder, identifying AKAP11 as a shared risk gene with schizophrenia through ultra-rare protein-truncating variants.

Weighted burden analysis in 200,000 exome-sequenced subjects characterises rare variant effects on risk of type 2 diabetes

The paper performs a weighted burden analysis of rare variants in 200,000 exome-sequenced UK Biobank participants to identify genes associated with type 2 diabetes risk.

Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of psychiatric referral

The paper analyzes exome data from 50,000 UK Biobank participants to find genes influencing psychiatric referral probability but finds no significant associations after correction for multiple testing.

Do damaging variants of SLC6A9, the gene for the glycine transporter 1 (GlyT-1), protect against schizophrenia?

The paper investigates whether damaging variants in SLC6A9, the gene for GlyT-1, are protective against schizophrenia by analyzing exome data from 4225 cases and 5834 controls.

Analysis of exome-sequenced UK Biobank subjects implicates genes affecting risk of hyperlipidaemia

The paper identifies genes associated with hyperlipidaemia risk using exome data from UK Biobank, finding significant associations with HUWE1 and other genes.

Weighted burden analysis of exome-sequenced late onset Alzheimer’s cases and controls provides further evidence for a role for PSEN1 and suggests involvement of the PI3K/Akt/GSK-3β and WNT signalling pathways

The paper uses weighted burden analysis on exome data from over 10,000 Alzheimer's cases and controls to find PSEN1 as a risk factor and suggest roles for PI3K/Akt/GSK-3β and WNT pathways.

LD scores are associated with differences in allele frequencies between populations but LD score regression can still distinguish confounding from polygenicity

The paper tests the assumption of LD score regression by showing a small association between LD scores and allele frequency differences between populations, but concludes that polygenic effects can still be distinguished from population stratification.

Multiple linear regression allows weighted burden analysis of rare coding variants in an ethnically heterogeneous population

The paper applies weighted burden analysis using multiple linear regression to rare coding variants in a heterogeneous population, finding that including population principal components reduces inflation in test statistics.

Variants in ACE2 and TMPRSS2 genes are not major determinants of COVID-19 severity in UK Biobank subjects

The paper analyzes exome data from UK Biobank subjects to assess if ACE2 and TMPRSS2 variants influence COVID-19 severity, finding no significant associations.

Genomewide association study identifies 30 loci associated with bipolar disorder

This study identifies 30 genome-wide significant loci associated with bipolar disorder, including novel genes involved in ion channels, neurotransmitters, and synaptic components.

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

The paper identifies 9 novel genetic loci, including low-frequency variants in TP53, associated with head circumference and intracranial volume in up to 46,000 individuals.

In silico investigation of coding variants potentially affecting the functioning of the glutamatergic N-methyl-D-aspartate receptor in schizophrenia

The paper investigates coding variants in NMDAR and related kinase genes in schizophrenia, finding few disruptive variants and some potential functional impacts in FYN and GRIN genes.

A weighted burden test using logistic regression for integrated analysis of sequence variants, copy number variants and polygenic risk score

The paper introduces a logistic regression-based weighted burden test to integrate sequence variants, copy number variants, and polygenic risk scores in disease association studies.

Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia

The paper shows that the schizophrenia polygenic risk score (PRS) varies significantly by ancestry, with African subjects having much higher scores than European subjects, suggesting the PRS contains a strong ancestry component.

Age at first birth in women is genetically associated with increased risk of schizophrenia

The paper finds a genetic association between schizophrenia risk and age at first birth in women, with different genetic correlations in younger and older age groups.