%0 Journal Article %J PLoS One %D 2017 %T Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort. %A Thalida E. Arpawong %A Pendleton, Neil %A Mekli, Krisztina %A John J McArdle %A Margaret Gatz %A Armoskus, Chris %A James A Knowles %A Carol A Prescott %K Cognitive Ability %K Genetics %K GWAS %K Memory %X Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996-2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory. %B PLoS One %V 12 %P e0182448 %8 2017 %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/28800603?dopt=Abstract %R 10.1371/journal.pone.0182448 %0 Journal Article %J Twin Research and Human Genetics %D 2013 %T The Project TALENT Twin and Sibling Study. %A Carol A Prescott %A Achorn, Deanna Lyter %A Kaiser, Ashley %A Mitchell, Lindsey %A John J McArdle %A Lapham, Susan J %K Education %K Genetics %K GWAS %K Siblings %X Project TALENT is a US national longitudinal study of about 377,000 individuals born in 1942-1946, first assessed in 1960. Students in about 1,200 schools participated in a 2-day battery covering aptitudes, abilities, interests, and individual and family characteristics (Flanagan, 1962; www.projectTALENT.org). Follow-up assessments 1, 5, and 11 years later assessed educational and occupational outcomes. The sample includes approximately 92,000 siblings from 40,000 families, including 2,500 twin pairs and 1,200 other siblings of twins. Until recently, almost no behavior genetic research has been conducted with the sample. In the original data collection information was not collected with the intent to link family members. Recently, we developed algorithms using names, addresses, birthdates, and information about family structure to link siblings and identify twins. We are testing several methods to determine zygosity, including use of yearbook photographs. In this paper, we summarize the design and measures in Project TALENT, describe the Twin and Sibling sample, and present our twin-sib-classmate model. In most twin and family designs, the 'shared environment' includes factors specific to the family combined with between-family differences associated with macro-level variables such as socioeconomic status. The school-based sampling design used in Project TALENT provides a unique opportunity to partition the shared environment into variation shared by siblings, specific to twins, and associated with school- and community-level factors. The availability of many measured characteristics on the family, schools, and neighborhoods enhances the ability to study the impact of specific factors on behavioral variation. %B Twin Research and Human Genetics %V 16 %P 437-448 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/23101474?dopt=Abstract %R 10.1017/thg.2012.71