The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

BACKGROUND:The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies.METHODS:Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests.RESULTS:The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 +/- 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency [greater than or equal to] 10%, genotype call rate [greater than or equal to] 80%, Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.

SomeCast: A Paradigm for Real-Time Adaptive Reliable Multicast

SomeCast is a novel paradigm for the reliable multicast of real-time data to a large set of receivers over the Internet. SomeCast is receiver-initiated and thus scalable in the number of receivers, the diverse characteristics of paths between senders and receivers (e.g. maximum bandwidth and round-trip-time), and the dynamic conditions of such paths (e.g. congestion-induced delays and losses). SomeCast enables receivers to dynamically adjust the rate at which they receive multicast information to enable the satisfaction of real-time QoS constraints (e.g. rate, deadlines, or jitter). This is done by enabling a receiver to join SOME number of concurrent multiCAST sessions, whereby each session delivers a portion of an encoding of the real-time data. By adjusting the number of such sessions dynamically, client-specific QoS constraints can be met independently. The SomeCast paradigm can be thought of as a generalization of the AnyCast (e.g. Dynamic Server Selection) and ManyCast (e.g. Digital Fountain) paradigms, which have been proposed in the literature to address issues of scalability of UniCast and MultiCast environments, respectively. In this paper we overview the SomeCast paradigm, describe an instance of a SomeCast protocol, and present simulation results that quantify the significant advantages gained from adopting such a protocol for the reliable multicast of data to a diverse set of receivers subject to real-time QoS constraints.