Goals and Objectives: This mission of the Fox lab is to have a better understanding of the metabolic risk factors for heart disease using the tools of population science. These tools included epidemiology, high-throughput biomarkers, imaging, and genetics and genomics. Several areas of intensive research are pursued, including obesity, ectopic fat depot imaging and body composition, diabetes, and chronic kidney disease. Summary: The overarching goal of the Fox lab is the study of metabolic risk factors and cardiovascular disease. As such, Dr. Fox works in three major content areas: obesity, diabetes, and chronic kidney disease. Her work spans traditional population science and genetic epidemiology. Obesity, Ectopic Fat, and Vascular Disease In terms of obesity, Dr. Fox has created a computed-tomography body composition database by using standard imaging techniques to assess abdominal visceral fat, pericardial fat, mediastinal fat, perivascular fat, fatty liver, and renal sinus fat. Her work focuses on both the systemic and local manifestations of body fat distribution, working with the concept that fat can have locally toxic effects on the vasculature and nearby anatomic structures. A cornerstone of Dr. Foxs work in this area has revolved around the mentoring of students, pre-doctoral fellows, post-doctoral fellows, and junior faculty members. Dr. Fox is also involved in the genetics and genomics of obesity and body composition. She is an active participant in the GIANT consortium, a genome-wide association consortium dedicated to uncovering genomic loci for anthropometric traits. Dr. Fox has also conducted GWAS of visceral and pericardial fat, which have also revealed unique loci for ectopic fat distribution. Because genome-wide association identifies single nucleotide polymorphisms that are common, sequencing studies can help uncover rare variants. As part of the CHARGE-S consortium, sequencing is ongoing for generalized obesity and body composition. Chronic Kidney Disease Dr. Fox also works to understand the role of chronic kidney disease. Dr. Fox is interested in traditional and novel risk factors for chronic kidney disease. Chronic kidney disease is an important risk factor for heart disease, and often is undetected. Thus, improving our ability to detect and predict chronic kidney disease is an important scientific goal. The Fox lab has recently developed a renal risk score, and showed that standard clinical risk factors including age, hypertension, diabetes, and proteinuria can improve our ability to predict who will develop kidney disease within a 10-year interval. Urinary biomarkers can provide insight into risk prediction, but also provide information regarding the location of renal injury, which may have prognostic significance. The Fox lab is now examining a panel of 14 urinary biomarkers. Parallel to epidemiologic and biomarker work, Dr. Fox leads the CHARGE and CARe renal working groups, two consortia which focus on the genetics of renal function. Dr. Fox is also the founder and convener of CKDGen, an international consortium dedicated to uncovering genes for renal disease. CKDGen includes more than 50 participating studies with over 30,000 individual participants and 250 investigators. This group is rapidly working to uncover even more genes for kidney disease. In the past year, this work has lead to the discovery of several new loci for renal function and related traits. This work has also evolved into sequencing, and the CHARGE-S consortium is sequencing 400 cases of chronic kidney disease. Finally, because genome-wide association offers a statistical association only, Dr. Fox has set up a collaboration with a zebra fish lab to begin to understand the functional consequences of some newly uncovered loci for renal function. Diabetes Finally, Dr. Fox works in the area of diabetes, primarily to understand trends in diabetes as a risk factor for heart disease, as well as treatment patterns over time. Dr. Fox is currently working on a lifecourse analysis to understanding the evolution of CVD risk factors associated with diabetes. Staff: Dr. Audrey Chu is a Staff Scientist in the Fox Lab. As a genetic epidemiologist, she primarily works on the genetics of CKD and diabetes. Dr. Jane Lee is a post-doctoral fellow in the Fox lab focusing on body composition. Dr. Jiantao Ma is a post-doctoral fellow in the Fox lab focusing on CKD and nutrition. Kate Therkelsen BA is a pre-doctoral fellow in the Fox lab focusing on obesity and metabolism. Dr. Gearoid Mac Mahon is a prior post-doctoral fellow in the Fox lab who is now serving as a Research collaborator (non clinical). As a nephrologist, his work focuses on chronic kidney disease. Dr. Klara Rosenquist is a Special Volunteer in the Fox lab. She is working primarily on the associations of ectopic fat depots and cardiovascular disease risk factors. Dr. Tobin Abraham is a Special Volunteer in the Fox lab. He is working on binge eating and metabolic risk factors.

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Mellinger, Jessica L; Pencina, Karol M; Massaro, Joseph M et al. (2015) Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study. J Hepatol 63:470-6
Shungin, Dmitry (see original citation for additional authors) (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518:187-196
Yeoh, Aaron J; Pedley, Alison; Rosenquist, Klara J et al. (2015) The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally. J Clin Endocrinol Metab 100:E1056-64
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Rosenquist, Klara J; Massaro, Joseph M; Pedley, Alison et al. (2015) Fat quality and incident cardiovascular disease, all-cause mortality, and cancer mortality. J Clin Endocrinol Metab 100:227-34
Murabito, Joanne M; Pedley, Alison; Massaro, Joseph M et al. (2015) Moderate-to-vigorous physical activity with accelerometry is associated with visceral adipose tissue in adults. J Am Heart Assoc 4:e001379
Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola et al. (2015) Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study. Diabetologia 58:988-96

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