@article{Wilman2017,
title = {Characterisation of liver fat in the UK Biobank cohort},
author = {Henry R. Wilman, Matt Kelly, Steve Garratt, Paul M. Matthews, Matteo Milanesi, Amy Herlihy, Micheal Gyngell, Stefan Neubauer, Jimmy D. Bell, Rajarshi Banerjee, E. Louise Thomas },
url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172921},
year = {2017},
date = {2017-02-27},
journal = {PLOS One },
abstract = {Non-alcoholic fatty liver disease and the risk of progression to steatohepatitis, cirrhosis and hepatocellular carcinoma have been identified as major public health concerns. We have demonstrated the feasibility and potential value of measuring liver fat content by magnetic resonance imaging (MRI) in a large population in this study of 4,949 participants (aged 45–73 years) in the UK Biobank imaging enhancement. Despite requirements for only a single (≤3min) scan of each subject, liver fat was able to be measured as the MRI proton density fat fraction (PDFF) with an overall success rate of 96.4%. The overall hepatic fat distribution was centred between 1–2%, and was highly skewed towards higher fat content. The mean PDFF was 3.91%, and median 2.11%. Analysis of PDFF in conjunction with other data fields available from the UK Biobank Resource showed associations of increased liver fat with greater age, BMI, weight gain, high blood pressure and Type 2 diabetes. Subjects with BMI less than 25 kg/m2 had a low risk (5%) of high liver fat (PDFF > 5.5%), whereas in the higher BMI population (>30 kg/m2) the prevalence of high liver fat was approximately 1 in 3. These data suggest that population screening to identify people with high PDFF is possible and could be cost effective. MRI based PDFF is an effective method for this. Finally, although cross sectional, this study suggests the utility of the PDFF measurement within UK Biobank, particularly for applications to elucidating risk factors through associations with prospectively acquired data on clinical outcomes of liver diseases, including non-alcoholic fatty liver disease.},
keywords = {9914, fat, imaging, liver},
pubstate = {published},
tppubtype = {article}
}

@misc{KARADERI2016,
title = {Exome chip meta-analysis identifies novel low-frequency variants contributing to central body fat distribution},
author = {T KARADERI, AE JUSTICE, KL YOUNG, HM HIGHLAND, M GRAFF, V TURCOT, P AUER, NL HEARD-COSTA, C SCHURMANN, Y LU, LA CUPPLES, CS FOX, TW WINKLER, N GRARUP, RA SCOTT, M MCCARTHY, K MOHLKE, RJF LOOS, I BORECKI, KE NORTH, CM LINDGREN, on behalf of the BBMRI, GOT2D, CHARGE, and GIANT Consortia.},
year = {2016},
date = {2016-04-07},
abstract = {Presented at the International Congress of Human Genetics in Kyoto, Japan.

Fat distribution is an important predictor of cardiometabolic disease risk. Evidence suggests genetic factors contribute to fat distribution, measured as waist-to-hip ratio adjusted for BMI (WHR). Forty-nine loci have been associated with WHR in previous genome-wide association studies (GWAS) targeting common variants [minor allele frequency (MAF)≥5%] mainly in European populations. Our aim was to identify low frequency coding variants (LFV, MAF<5%) associated with WHR using exome chip data from 344,369 individuals of European, African, Asian, and Hispanic descent. Fixed effects meta-analyses stratified by sex and ancestry were performed, and also combined for single nucleotide variant (SNV) and gene-based results. Gene-based analyses used a strict definition of non-synonymous and missense SNVs annotated as damaging by 5 algorithms. Analyses included up to 246,329 SNVs (218,195 with MAF<5%), and 9,268 genes. Conditional analyses were carried out to detect novel associations independent of the previously known GWAS signals. Associations with four out of five LFVs (RAPGEF3, MAF=0.01, β=-0.09, P=1.3E-13; KIAA0408, MAF=0.009, β=0.11, P=2.1E-13; HIST1H1T, MAF=0.001, β=0.23, P=4.3E-8; FGFR2, MAF=0.001, β=0.26, P=1.4E-7) reaching chip-wide significance (P<2.5E-7) in the all-ancestry sex-combined analysis were novel. RAPGEF3 was also significantly associated with WHR (β=-0.08, P=6.9E-14) and BMI (β=0.05, P=4.7E-12) in the gene-based analysis. RAPGEF3 and FGFR2 are expressed in adipose tissue and the brain, respectively. RAPGEF3 plays a role in the GLP1 pathway controlling insulin secretion. FGFR2 controls a range of biological processes by regulating cell proliferation and differentiation, and is implicated in birth weight. Our results highlight the importance of targeting LFVs in large studies to detect potentially functional variants. Dissecting these associations may identify possible population-specific variants providing insights into the physiology of central adiposity.


},
keywords = {1251, fat, genetics},
pubstate = {published},
tppubtype = {presentation}
}

@article{RiderOJ2016,
title = {Investigating a Liver Fat: Arterial Stiffening Pathway in Adult and Childhood Obesity},
author = {Rider, O. J.
Banerjee, R.
Rayner, J. J.
Shah, R.
Murthy, V. L.
Robson, M. D.
Neubauer, S.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26564820},
year = {2015},
date = {2015-11-14},
journal = {Arterioscler Thromb Vasc Biol},
abstract = {OBJECTIVE: To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. APPROACH AND RESULTS: Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/m(2); percentile 8-100) with no identifiable cardiac risk factors underwent; 1H- magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (beta=0.09; P=0.02), liver fat (beta=2.5; P=0.04), and serum triglyceride (beta=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=-0.35; descending, r=-0.23; abdominal, r=-0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=-0.52; P<0.001) were correlated with liver fat in children. CONCLUSIONS: Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity.},
keywords = {arterial stiffening, fat, liver},
pubstate = {published},
tppubtype = {article}
}