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12 papers found.
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The role of glycaemic and lipid risk factors in mediating the effect of BMI on coronary heart disease: a two-step, two-sample Mendelian randomisation study

Aims/hypothesis The extent to which effects of BMI on CHD are mediated by glycaemic and lipid risk factors is unclear. In this study we examined the effects of these traits using genetic evidence. Methods We used two-sample Mendelian randomisation to determine: (1) the causal effect of BMI on CHD (60,801 case vs 123,504 control participants), type 2 diabetes (34,840 case vs 114,981 ...

Shared genetic control of expression and methylation in peripheral blood

Background Expression QTLs and epigenetic marks are often employed to provide an insight into the possible biological mechanisms behind GWAS hits. A substantial proportion of the variation in gene expression and DNA methylation is known to be under genetic control. We address the proportion of genetic control that is shared between these two genomic features. Results An exhaustive ...

Mendelian randomization: genetic anchors for causal inference in epidemiological studies

George Davey Smith 0 Gibran Hemani 0 0 MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine , Bristol, UK Observational epidemiological

Systematic identification of genetic influences on methylation across the human life course

Integrative Epidemiology Unit (IEU) & School of Social and Community Medicine, University of Bristol , Oakfield House, Oakfield Grove, Bristol BS8 2BN , UK 1 Tom R. Gaunt, Hashem A. Shihab, Gibran Hemani

An Evolutionary Perspective on Epistasis and the Missing Heritability

The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epistasis, the majority of the genetic variance that will persist is actually ...

Prenatal and early life influences on epigenetic age in children: a study of mother–offspring pairs from two cohort studies

DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using ...

Contribution of genetic variation to transgenerational inheritance of DNA methylation

Background Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to ...

Statistical Power to Detect Genetic (Co)Variance of Complex Traits Using SNP Data in Unrelated Samples

We have recently developed analysis methods (GREML) to estimate the genetic variance of a complex trait/disease and the genetic correlation between two complex traits/diseases using genome-wide single nucleotide polymorphism (SNP) data in unrelated individuals. Here we use analytical derivations and simulations to quantify the sampling variance of the estimate of the proportion of ...

EpiGPU: exhaustive pairwise epistasis scans parallelized on consumer level graphics cards

Motivation: Hundreds of genome-wide association studies have been performed over the last decade, but as single nucleotide polymorphism (SNP) chip density has increased so has the computational burden to search for epistasis [for n SNPs the computational time resource is O(n(n−1)/2)]. While the theoretical contribution of epistasis toward phenotypes of medical and economic ...

Genome-wide association study of blood lead shows multiple associations near ALAD

Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but ...

Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted—in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We ...

Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates

Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise ...