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Framingham Center, MA, United States

Therkelsen K.E.,Boston University | Therkelsen K.E.,Lung and Blood Institutes NHLBI Framingham Heart Study | Pedley A.,Lung and Blood Institutes NHLBI Framingham Heart Study | Speliotes E.K.,University of Michigan | And 5 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE: Intramuscular fat accumulates between muscle fibers or within muscle cells. We investigated the association of intramuscular fat with other ectopic fat deposits and metabolic risk factors. APPROACH AND RESULTS: Participants (n=2945; 50.2% women; mean age 50.8 years) from the Framingham Heart Study underwent multidetector computed tomography scanning of the abdomen. Regions of interest were placed on the left and right paraspinous muscle, and the muscle attenuation (MA) in Hounsfield units was averaged. We examined the association between MA and metabolic risk factors in multivariable models, and additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT) in separate models. MA was associated with dysglycemia, dyslipidemia, and hypertension in both sexes. In women, per standard deviation decrease in MA, there was a 1.34 (95% confidence interval, 1.10-1.64) increase in the odds of diabetes mellitus, a 1.40 (95% confidence interval, 1.22-1.61) increase in the odds of high triglycerides, and a 1.29 (95% confidence interval, 1.12-1.48) increase in the odds of hypertension. However, none of these associations persisted after adjustment for BMI or VAT. In men, we observed similar patterns for most risk factors. The exception was metabolic syndrome, which retained association in women even after adjustment for BMI and VAT, and low high density lipoprotein and high triglycerides in men, whose associations also persisted after adjustment for BMI and VAT. CONCLUSIONS: MA was associated with metabolic risk factors, but most of these associations were lost after adjustment for BMI or VAT. However, a unique association remained for metabolic syndrome in women and lipids in men. © 2013 American Heart Association, Inc.


Sotoodehnia N.,University of Washington | Isaacs A.,Erasmus Medical Center | Isaacs A.,Center for Medical Systems Biology | De Bakker P.I.W.,Harvard University | And 131 more authors.
Nature Genetics | Year: 2010

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10 -8). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction. © 2010 Nature America, Inc. All rights reserved.

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