13 research outputs found

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

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    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

    LODENet:a holistic approach to offline handwritten Chinese and Japanese text line recognition

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    Abstract One of the biggest obstacles in Chinese and Japanese text line recognition is how to present their enormous character sets. The most common solution is to merely choose and represent a small subset of characters using one-hot encoding. However, such an approach is costly to describe huge character sets, and ignores their semantic relationships. Recent studies have attempted to utilize different encoding methods, but they struggle to build a bijection mapping. In this work, we propose a novel encoding method, called LOgographic DEComposition encoding (LODEC), that can efficiently perform a 1-to-1 mapping for all Chinese and Japanese characters. As such, LODEC enables to encode over 21,000 Chinese and Japanese characters by 520 fundamental elements. Moreover, to handle the vast style variety of handwritten texts in the two languages, we propose a novel deep learning (DL) architecture, called LODENet, together with an end-to-end training scheme, that leverages auxiliary ground truths generated by LODEC or other radical-based encoding methods. We systematically performed experiments on both Chinese and Japanese datasets, and found that our approach surpassed the performance of state-of-the-art baselines. Furthermore, empirical evidence shows that our method can gain significantly improvement using synthesized text line images without the need for domain knowledge
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