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.

Singing Through Struggle: Music as a Mode of Cultural Exchange in African American Border City Churches After Emancipation, 1862-1890

This project investigates how religious music, invested with symbolic and cultural meaning, provided African Americans in border city churches with a way to negotiate conflict, assert individual values, and establish a collective identity in the post- emancipation era. In order to focus on the encounter between former slaves and free Blacks, the dissertation examines black churches that received large numbers of southern migrants during and after the Civil War. Primarily a work of history, the study also employs insights and conceptual frameworks from other disciplines including anthropology and ritual studies, African American studies, aesthetic theory, and musicology. It is a work of historical reconstruction in the tradition of scholarship that some have called "lived religion." Chapter 1 introduces the dissertation topic and explains how it contributes to scholarship. Chapter 2 examines social and religious conditions African Americans faced in Baltimore, MD, Philadelphia, PA, and Washington, DC to show why the Black Church played a key role in African Americans' adjustment to post-emancipation life. Chapter 3 compares religious slave music and free black church music to identify differences and continuities between them, as well as their functions in religious settings. Chapters 4, 5, and 6 present case studies on Bethel African Methodist Episcopal Church (Baltimore), Zoar Methodist Episcopal Church (Philadelphia), and St. Luke’s Protestant Episcopal Church (Washington, DC), respectively. Informed by fresh archival materials, the dissertation shows how each congregation used its musical life to uphold values like education and community, to come to terms with a shared experience, and to confront or avert authority when cultural priorities were threatened. By arguing over musical choices or performance practices, or agreeing on mutually appealing musical forms like the gospel songs of the Sunday school movement, African Americans forged lively faith communities and distinctive cultures in otherwise adverse environments. The study concludes that religious music was a crucial form of African American discourse and expression in the post-emancipation era. In the Black Church, it nurtured an atmosphere of exchange, gave structure and voice to conflict, helped create a public sphere, and upheld the values of black people.