Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

A Catechumenate for the Korean Methodist Church: Ressourcement, Formation and a Response to Secularism and Korean Traditional Religions

Research by Korean sociologists of religion indicates that Korean Protestantism has lost much of the spiritual vitality of preceding generations and that it increasingly shows the influences of Korean shamanism, Neo-Confucianism, and Western secularism and consumerism. Suggestions in the areas of homiletics and Christian social ethics have been offered to help steer the Korean Protestant churches away from these worldviews toward a more biblically-based course. Drawing upon and expanding these earlier studies and proposals, the current work recommends another method for developing a biblically-based, spiritually-revitalized, baptismally-shaped and ministry-committed Protestantism in Korea: a pre-baptismal adult catechumenate, in this case one designed for the context of the Korean Methodist Church. In order to produce a renewed catechumenal structure for Korean Methodism, adult catechumenal processes as well as baptismal theologies and rites are examined and analyzed from three principal sources: the first five centuries of the Christian church, and especially the mystagogical literature of the fourth century; the Roman Catholic Rite of Christian Initiation of Adults developed after the Second Vatican Council; and the United Methodist Church in the United States, both texts officially authorized by the denomination's General Conference and unofficial materials, among them resources for an adult catechumenate in the Come to the Waters series. In addition, previous and current practices of preparation for baptism in the Korean Methodist Church are identified and critiqued. From these findings a set of principles is put forward that guide the proposed catechumenal structure.