Crossbreeding studies in rodents have identified numerous quantitative trait loci (QTL) that are linked to diabetes-related component traits. To identify genetic consensus regions implicated in insulin action and glucose homeostasis, we have performed a meta-analysis of genomewide linkage scans for diabetes-related traits. From a total of 43 published genomewide scans we assembled a nonredundant collection of 153 QTL for glucose levels, insulin levels, and glucose tolerance. Collectively, these studies include data from 48 different parental strains and >11,000 individual animals. The results of the studies were analyzed by the truncated product method (TPM). The analysis revealed significant evidence for linkage of glucose levels, insulin levels, and glucose tolerance to 27 different segments of the mouse genome. The most prominent consensus regions [localized to chromosomes 2, 4, 7, 9, 11, 13, and 19; logarithm of odds (LOD) scores 10.5-17.4] cover approximately 11% of the mouse genome and collectively contain the peak markers for 47 QTL. Approximately half of these genomic segments also show significant linkage to body weight and adiposity, indicating the presence of multiple obesity-dependent and -independent consensus regions for diabetes-related traits. At least 84 human genetic markers from genomewide scans and >80 candidate genes from human and rodent studies map into the mouse consensus regions for diabetes-related traits, indicating a substantial overlap between the species. Our results provide guidance for the identification of novel candidate genes and demonstrate the presence of numerous distinct consensus QTL regions with highly significant LOD scores that control glucose homeostasis. An interactive physical map of the QTL is available online at http://www.diabesitygenes.org.
The Robert Wood Johnson Foundation (RWJF) (http://www.rwjf.org/en.html) launched Healthy Kids, Healthy Communities (HKHC) in 2008, with a $33.4 million commitment to help reverse the childhood obesity epidemic by 2015. With grant funding and technical assistance, HKHC supported 50 diverse community partnerships focusing on populations at greatest risk for obesity. Active Living By Design served as the national program office, and St. Louis-based Transtria conducted the evaluation. Collaboration fundamentally shaped HKHC's national program design and strategy, the grantee selection process, technical assistance, the HKHC learning network, and evaluation. This article describes the ways in which the concept of collaboration was defined and practiced among the Robert Wood Johnson Foundation, Active Living By Design, Transtria, and other national partners, and how it shaped the evolving vision for and expectations from HKHC grantees. Collaboration contributed to HKHC grantees' success, helped build the healthy communities movement, and influenced philanthropic practices.
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