A5039824180- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Cancer, Lipids, and Metabolism
- Genetics and Neurodevelopmental Disorders
- Osteoarthritis Treatment and Mechanisms
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Advanced Proteomics Techniques and Applications
- Blood Coagulation and Thrombosis Mechanisms
- Genetic and phenotypic traits in livestock
- Gene expression and cancer classification
- Inflammatory mediators and NSAID effects
- Venous Thromboembolism Diagnosis and Management
- Ubiquitin and proteasome pathways
- Nutrition, Genetics, and Disease
- Glycosylation and Glycoproteins Research
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Syndromes and Imprinting
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- Genetics and Physical Performance
- Skin and Cellular Biology Research
- Chronic Kidney Disease and Diabetes
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
MRC Epidemiology Unit
2021-2025
University of Cambridge
2018-2025
Queen Mary University of London
2024-2025
Istanbul Technical University
2021-2023
Boğaziçi University
2020
Wellcome Sanger Institute
2018-2019
Detangling gene-disease connections Many diseases are at least partially due to genetic causes that not always understood or targetable with specific treatments. To provide insight into the biology of various human as well potential leads for therapeutic development, Pietzner et al . undertook detailed, genome-wide proteogenomic mapping. The authors analyzed thousands between disease-associated mutations, proteins, and medical conditions, thereby providing a detailed map use by future...
Abstract Affinity-based proteomics has enabled scalable quantification of thousands protein targets in blood enhancing biomarker discovery, understanding disease mechanisms, and genetic evaluation drug humans through quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques—the aptamer-based SomaScan ® v4 assay the antibody-based Olink assays—to systematically assess phenotypic consequences hundreds pQTLs discovered for 871 across both platforms. We create a...
Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for prevention. We investigate 2,074 circulating risk of nine common cancers (bladder, breast, endometrium, head neck, lung, ovary, pancreas, kidney, malignant non-melanoma) using cis protein Mendelian randomisation colocalization. conduct additional analyses adverse side-effects altering map drug targets. Here we find 40 associated with cancers, such as PLAUR breast [odds ratio per standard deviation...
Genetic studies of human metabolism identified unknown disease processes and novel metabolic regulators, but have been limited in scale allelic breadth. Here, we provide a data–driven map the genetic regulation circulating small molecules lipoprotein characteristics (249 traits) measured using protein nuclear magnetic resonance spectroscopy (1H–NMR) across allele frequency spectrum ~450.000 individuals. In trans–ancestry analyses, identify 29,824 locus–metabolite associations mapping to 753...
PurposeThe study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, characterize their risks of adverse health outcomes.MethodsWe analyzed genotyping array or exome sequence data in 207,067 men European ancestry aged 40 70 years from the UK Biobank related these extensive routine record data.ResultsOnly 49 213 (23%) whom we identified with KS only 1 143 (0.7%) 47,XYY had a diagnosis abnormal karyotype on medical records...
Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for prevention. We investigated association 2002 genetically predicted protein levels with overall, aggressive early onset disease, using cis-pQTL Mendelian randomisation (MR) colocalisation. Findings support from both MR, after correction multiple-testing, colocalisation were replicated two independent GWAS, one European African ancestry. Proteins evidence...
Abstract Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form clonal mosaicism, caused by dysregulation cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that function two genes— CHEK2 GIGYF1 —reach exome-wide significance. Rare alleles not previously been implicated any...
Abstract Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there need for improved plasma biomarker-based tools VTE diagnosis risk prediction. Here we show, using proteomics profiling to screen from patients suspected acute VTE, several case-control studies how Complement Factor H Related 5 protein (CFHR5), regulator of the alternative pathway complement activation, VTE-associated biomarker....
Proteomic techniques now measure thousands of circulating proteins at population scale, driving a surge in biomarker studies and biological clocks. However, their potential impact, generalisability, relevance is hard to assess without understanding the origins role implicated these studies. Here, we provide data-driven identification foundations protein variation that underly links ageing diseases, differ between sexes ancestries, help guide drug target discovery. We use machine learning...
Abstract To better understand sex differences in human health and disease, we conducted a systematic, large-scale investigation of the genetic regulation plasma proteome (>5,000 targets), including their disease relevance. Plasma levels two-thirds protein targets differed significantly by sex. In contrast, effects on were remarkably similar, with very few quantitative loci (pQTLs, n=74) showing significant sex-differential (for 3.9% 0.3% from antibody- aptamer-based platforms,...
ABSTRACT Discovery of protein quantitative trait loci (pQTLs) has been enabled by affinity-based proteomic techniques and is increasingly used to guide genetically informed drug target evaluation. Large-scale data are now being created, but systematic, bidirectional assessment platform differences lacking, restricting clinical translation. We compared genetic, technical, phenotypic determinants 871 targets measured using both aptamer-(SomaScan® Platform v4) antibody-based (Olink) assays in...
Abstract Context Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant metabolic health, have been limited by the difficulty in linking predominantly noncoding variants to specific gene targets. Rare coding variant analyses provide greater confidence that is involved, but do not necessarily indicate whether gain or loss function (LoF) would be most therapeutic benefit. Objective This work aimed identify genes/proteins...
Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for prevention.
Abstract Fraser syndrome is characterized by cryptophthalmos, syndactyly and other autopod defects, abnormalities of the respiratory urogenital tracts. Biallelic variants in GRIP1 can cause 3 (FRASRS3), five unrelated FRASRS3 cases have been reported to date. Four are fetuses with homozygous truncating variants. The remaining case an almost 9‐year‐old Turkish girl compound heterozygous for a truncation variant possibly frame‐shift intragenic deletion. We present 15.5‐year old Pakistani boy...
Abstract Background Understanding the role of circulating proteins in cancer risk can reveal key biological pathways and identify novel therapeutic targets for prevention. Methods We investigated associations 2,094 with nine common cancers (bladder, breast, endometrium, head neck, lung, ovary, pancreas, kidney, malignant non-melanoma) using cis pQTL Mendelian randomisation (MR) colocalization. Findings support from both MR, after correction multiple-testing, colocalization were replicated an...
ABSTRACT Heterotopic ossification (HO) is bone formation that occurs after trauma within tissues do not normally have the property of ossification, resulting in pain and disability. The genetic architecture HO remains unclear. In first genome-wide association studies this disease, we identify human-only long non-coding RNA-encoding gene CASC20 as a robust, replicating susceptibility locus for KIF26B potential severity locus. We find both are expressed human bone. Both expression upregulated...
Abstract Genome-wide association studies (GWAS) in predominately European-ancestry (EUR) populations have identified numerous genetic variants associated with adiposity-related traits. An emerging challenge is the limited transferability of scores constructed based on GWAS results from one ancestry for trait prediction other ancestries. We performed trans-ancestry meta-analysis (TAMA) eight traits using data 96,124 East Asian (EAS) and 443,359 EUR individuals. >1400 genomic regions...