Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.Diabetes UK RD Lawrence fellowship, European Research Council, Wellcome Trust and Royal Society grant, European Regional Development Fund, Medical Research Council, German Federal Ministry of Education and Research, German Research Foundation, Innovative Medicines Initiative Joint Undertaking, European Union's Seventh Framework Programme, Dutch Science Organisation, Scottish Government Health Directorates, Scottish Funding Council and Medical Research Council UK and the Wellcome Trust

Distribution and quantification of human herpesvirus 6 in multiple sclerosis and control brains

Multiple sclerosis (MS) is thought to be precipitated by environmental factors, potentially including viruses, in genetically susceptible individuals and recently human herpesvirus 6 (HHV-6) has been associated with the disease. We have analysed post mortem brain for the presence, variant type and quantity of HHV-6 by PCR. A total of 124 samples from seven anatomically defined regions of brain were tested from MS cases and controls. HHV-6 DNA was detected in 41% and 44% of MS case and control samples. The median viral loads were 11 and 9 genome copies/mg DNA in cases and controls respectively and the viral load was not increased in lesions. Except in one instance, the HHV-6 DNA detected was variant B. There was no apparent difference in the distribution of HHV-6 DNA in the brains of MS cases versus controls, nor between normal appearing and lesional tissue in MS cases. Periventricular regions of the brain were more frequently positive for HHV-6 DNA in both MS cases and controls, although this difference was not statistically significant. These studies confirm the neurotropism of HHV-6 but do not demonstrate differences in the distribution, variant type or quantity of HHV-6 in brains from patients with MS versus controls