Mark I. McCarthy
University of Oxford
Publications 1233
#1Robert W. Koivula (University of Oxford)H-Index: 8
#2Naeimeh Atabaki-Pasdar (Lund University)H-Index: 3
Last.Søren Brunak (DTU: Technical University of Denmark)H-Index: 91
view all 34 authors...
It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the tw...
There is particular interest in transcriptome-wide association studies (TWAS) gene-level tests based on multi-SNP predictive models of gene expression—for identifying causal genes at loci associated with complex traits. However, interpretation of TWAS associations may be complicated by divergent effects of model SNPs on phenotype and gene expression. We developed an iterative modeling scheme for obtaining multi-SNP models of gene expression and applied this framework to generate expression model...
#1Melina Claussnitzer (Broad Institute)H-Index: 14
#2Melina Claussnitzer (Broad Institute)H-Index: 1
Last.Mark I. McCarthyH-Index: 162
view all 18 authors...
A primary goal of human genetics is to identify DNA sequence variants that influence biomedical traits, particularly those related to the onset and progression of human disease. Over the past 25 years, progress in realizing this objective has been transformed by advances in technology, foundational genomic resources and analytical tools, and by access to vast amounts of genotype and phenotype data. Genetic discoveries have substantially improved our understanding of the mechanisms responsible fo...
2 CitationsSource
#1Agata Wesolowska-Andersen (University of Oxford)H-Index: 2
#2Agata Wesolowska-Andersen (University of Oxford)H-Index: 1
Last.Christian Honoré (Novo Nordisk)H-Index: 7
view all 13 authors...
Summary Several distinct differentiation protocols for deriving pancreatic progenitors (PPs) from human pluripotent stem cells have been described, but it remains to be shown how similar the PPs are across protocols and how well they resemble their in vivo counterparts. Here, we evaluated three differentiation protocols, performed RNA and assay for transposase-accessible chromatin using sequencing on isolated PPs derived with these, and compared them with fetal human pancreas populations. This e...
#1Katherine Minjee Chung (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Jaffarguribal Singh (Yale University)
Last.Mandar Deepak Muzumdar (Yale University)
view all 23 authors...
Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how obesity contributes to pancreatic cancer development is not well understood. Moreover, whether and at what point weight loss or other obesity-related interventions may impact PDAC progression remains largely unexplored, with significant implications for prevention and treatment. Leveraging an autochthonous genetically engineered model of PDAC, we demonstrate that obesity plays a stage-specific causal a...
#1Michael Wainberg (Stanford University)H-Index: 6
#2Anubha Mahajan (University of Oxford)H-Index: 47
Last.Manuel A. Rivas (Stanford University)H-Index: 29
view all 7 authors...
Background Lifestyle interventions to reduce body mass index (BMI) are critical public health strategies for type 2 diabetes prevention. While weight loss interventions have shown demonstrable benefit for high-risk and prediabetic individuals, we aimed to determine whether the same benefits apply to those at lower risk. Methods and findings We performed a multi-stratum Mendelian randomization study of the effect size of BMI on diabetes odds in 287,394 unrelated individuals of self-reported white...
#1Robin G Walters (University of Oxford)H-Index: 3
#2David W. Clark (Edin.: University of Edinburgh)H-Index: 6
Last.James F. Wilson (Edin.: University of Edinburgh)H-Index: 107
view all 436 authors...
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32...
1 CitationsSource
#1Paul Petrus (KI: Karolinska Institutet)H-Index: 5
#2Simon Lecoutre (KI: Karolinska Institutet)H-Index: 2
Last.Mikael Rydén (KI: Karolinska Institutet)H-Index: 43
view all 20 authors...
Summary While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear. We hypothesized that the local metabolic environment could be an important determinant. To this end, we compared metabolites released from WAT of 81 obese and non-obese women. This identified glutamine to be downregulated in obesity and inversely associated with a pernicious WAT phenotype. Glutamine administration in vitro and in vivo attenuate...
1 CitationsSource
#1Alberto Romagnoni ('ENS Paris': École Normale Supérieure)H-Index: 15
Last.Pamela WhittakerH-Index: 31
view all 340 authors...
Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the interna...
#1Miriam S. UdlerH-Index: 11
#2Mark I. McCarthy (University of Oxford)H-Index: 162
Last.Anubha Mahajan (University of Oxford)H-Index: 47
view all 4 authors...
During the last decade, there have been substantial advances in the identification and characterization of DNA sequence variants associated with individual predisposition to type 1 and type 2 diabetes. As well as providing insights into the molecular, cellular, and physiological mechanisms involved in disease pathogenesis, these risk variants, when combined into a polygenic score, capture information on individual patterns of disease predisposition that have the potential to influence clinical m...
4 CitationsSource