Successful Aging Shows Linkage to Chromosomes 6, 7, and 14 in the Amish

Abstract

SUMMARY Successful aging (SA) is a multi-dimensional phenotype involving preservation of cognitive ability, physical function, and social engagement throughout life. Multiple components of SA are heritable, supporting a genetic component. The Old Order Amish are genetically and socially isolated with homogeneous lifestyles, making them a suitable population for studying the genetics of SA. DNA and measures of SA were collected on 214 cognitively intact Amish individuals over age 80. Individuals were grouped into a 13-generation pedigree using the Anabaptist Genealogy Database. A linkage screen of 5,944 single nucleotide polymorphisms (SNPs) was performed using 12 informative sub-pedigrees with an affected-only 2-point and multipoint linkage analysis. Eleven SNPs produced 2-point LOD scores >2, suggestive of linkage. Multipoint linkage analyses, allowing for heterogeneity, detected significant lod scores on chromosomes 6 (HLOD = 4.50), 7 (LOD* = 3.11), and 14 (HLOD = 4.17), suggesting multiple new loci underlying SA.

Rare Variant APOC3 R19X Is Associated With Cardio-Protective Profiles in a Diverse Population-Based Survey as Part of the Epidemiologic Architecture for Genes Linked to Environment Study

“…Study population characteristics of the Old Order Amish have been previously described 15 . Briefly, the Amish immigrated to the United States from Europe in two waves.…”

Linkage and association of successful aging to the 6q25 region in large Amish kindreds

“…In the current sample of 74 SA cases, genotyped for a much denser map of markers, the strongest evidence for linkage was obtained in a different area of chromosome 6. This region, near FRA6E, did provide modest evidence for linkage (MHLOD01.10-2.09) in our original study, indicating that the expanded sample improved power to detect linkage (Velez Edwards et al 2011). The difference in evidence for linkage across the three models considered (dominant, recessive, and nonparametric allele-sharing) may reflect differences in the goodness of fit for each model given different modes of inheritance.…”

“…We previously reported evidence for linkage of SA to chromosomes 6, 7, and 14 in a smaller subset of the sample (48 SA cases) used here (Velez Edwards et al 2011). In the current sample of 74 SA cases, genotyped for a much denser map of markers, the strongest evidence for linkage was obtained in a different area of chromosome 6.…”

“…The only exclusion criterion for the SA arm of the study was cognitive impairment (individuals screening cognitively impaired were referred to the dementia arm of the study). The recruitment and ascertainment methods for CAMP have been previously described (Pericak-Vance et al 1996;Velez Edwards et al 2011).…”

“…SA was defined as previously described (Velez Edwards et al 2011), considering functioning in all three domains described by Rowe and Kahn (1997). The specific criteria we used are outlined in Table 1.…”