ORCID Profile
0000-0002-0970-2610
Current Organisations
The University of Edinburgh
,
University of St Andrews
,
University of Manchester
,
Optima Partners Limited
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Publications
Systematic discovery of gene-environment interactions underlying the human plasma proteome in UK Biobank
Publisher: Cold Spring Harbor Laboratory
Date: 26-10-2023
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
Publisher: Springer Science and Business Media LLC
Date: 23-11-2020
Genetic map of regional sulcal morphology in the human brain from UK biobank data
Publisher: Springer Science and Business Media LLC
Date: 14-10-2022
DOI: 10.1038/S41467-022-33829-1
Abstract: Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 in iduals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease.
Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
Publisher: Springer Science and Business Media LLC
Date: 16-03-2021
Genetic map of regional sulcal morphology in the human brain
Publisher: Cold Spring Harbor Laboratory
Date: 15-10-2021
DOI: 10.1101/2021.10.13.463489
Abstract: The human brain is a complex organ underlying many cognitive and physiological processes, affected by a wide range of diseases. Genetic associations with macroscopic brain structure are emerging, providing insights into genetic sources of brain variability and risk for functional impairments and disease. However, specific associations with measures of local brain folding, associated with both brain development and decline, remain under-explored. Here we carried out detailed large-scale genome-wide associations of regional brain cortical sulcal measures derived from magnetic resonance imaging data of 40,169 in iduals in the UK Biobank. Combining both genotyping and whole-exome sequencing data (∼12 million variants), we discovered 388 regional brain folding associations across 77 genetic loci at p ×10 −8 , which replicated at p .05. We found genes in associated loci to be independently enriched for expression in the cerebral cortex, neuronal development processes and differential regulation in early brain development. We integrated coding associations and brain eQTLs to refine genes for various loci and demonstrated shared signal in the pleiotropic KCNK2 locus with a cortex-specific KCNK2 eQTL. Genetic correlations with neuropsychiatric conditions highlighted emerging patterns across distinct sulcal parameters and related phenotypes. We provide an interactive 3D visualisation of our summary associations, making complex association patterns easier to interpret, and emphasising the added resolution of regional brain analyses compared to global brain measures. Our results offer new insights into the genetic architecture underpinning brain folding and provide a resource to the wider scientific community for studies of pathways driving brain folding and their role in health and disease.
Blood protein levels predict leading incident diseases and mortality in UK Biobank
Publisher: Cold Spring Harbor Laboratory
Date: 03-05-2023
DOI: 10.1101/2023.05.01.23288879
Abstract: The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality, over 16 years of electronic health linkage in the UK Biobank (N=47,600). We report 3,201 associations between 961 protein levels and 21 incident outcomes, identifying proteomic indicators of multiple morbidities. Next, protein-based scores (ProteinScores) are developed using penalised Cox regression. When applied to test sets, six ProteinScores improve Area Under the Curve (AUC) estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically-relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperformed a polygenic risk score, a metabolomic score and HbA1c – a clinical marker used to monitor and diagnose type 2 diabetes. These data characterise early proteomic contributions to major age-related disease and demonstrate the value of the plasma proteome for risk stratification.
isGWAS: ultra-high-throughput, scalable and equitable inference of genetic associations with disease
Publisher: Cold Spring Harbor Laboratory
Date: 25-07-2023
DOI: 10.1101/2023.07.21.550074
Abstract: Genome-wide association studies (GWAS) have proven a powerful tool for human geneticists to generate biological insights or hypotheses for drug discovery. Nevertheless, a dependency on sensitive in idual-level data together with ever-increasing cohort s le sizes, numbers of variants and phenotypes studied put a strain on existing algorithms, limiting the GWAS approach from maximising potential. Here we present in-silico GWAS (isGWAS), a uniquely scalable algorithm to infer regression parameters in case-control GWAS from cohort-level summary data. For any s le size, isGWAS computes a variant-disease association parameter in ∼1 millisecond, or ∼11m variants in UK-Biobank within ∼4 minutes (∼1500-fold faster than state-of-the-art). Extensive simulations and empirical tests demonstrate that isGWAS results are highly comparable to traditional regression-based approaches. We further introduce a heuristic re-s ling algorithm, leapfrog re-s ler (LRS), to extrapolate association results to semi-virtually enlarged cohorts. Owing to significant computational gains we anticipate a broad use of isGWAS and LRS which are customizable on a web interface.
Related Organisations
The University Of Edinburgh
Location: United Kingdom of Great Britain and Northern Ireland
University Of St Andrews
Location: United Kingdom of Great Britain and Northern Ireland
University Of Manchester
Location: United Kingdom of Great Britain and Northern Ireland
University Of Cambridge
Location: United Kingdom of Great Britain and Northern Ireland
Optima Partners Limited
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Christopher Neal Foley.