O4‐01‐03: Genome‐Wide Association Study (GWAS) of plasma Aß levels in the dalmatian islands of Vis and korcula
Year: 2009
Type: article
Study design: Observational Study
Abstract: Plasma levels of the Aß protein show significant heritability in LOAD families [Ertekin-Taner et al, 2001]. Here we describe genome-wide association analysis of over 300,000 SNPs with plasma Aß40 and Aß42 levels in 960 subjects from the Dalmatian island of Vis. Genome-wide association analysis of plasma Aß levels in a second isolate from the neighboring island of Korcula is underway. These studies may reveal novel quantitative trait loci that influence plasma Aß levels and provide excellent candidate loci for studies of genetic association with LOAD. Plasma Aß levels were measured for all subjects in duplicate using a well established sandwich ELISA [Suzuki.N et al 1994]. The Vis subjects were initially genotyped for 810 Short Tandem Repeat markers, using an Applied Biosystems 5cM panel, and subsequently 317,503 SNPs were genotyped using the Illumina HumanHap300 chip. The Korcula subjects were genotyped for 318,237 SNPs using the Illumina Hap370cnv chip. Heritability estimates for Vis were determined using the variance components methodology implemented in SOLAR [Almasy & Blangero, 1998]. The R statistical library GenABEL [Aulchenko.Y et al, 2007] was used for genome wide association analysis for both populations. Plasma levels of Aß42 were determined to be a heritable quantitative trait in the Vis population (H2 = 20.8%, p = 0.036). Initial analysis of the Vis dataset failed to identify SNPs which associated with plasma Aß levels after Bonferonni correction for 317,503 SNPs tested. However in a separate, follow-up study of the Aß degrading enzyme and LOAD candidate gene, IDE, significant association with decreased plasma Aß40 (p = 0.03) and Aß42 (p = 0.02) was detected for a SNP (rs7910977), previously shown to be significantly associated with increased IDE expression and decreased risk for LOAD (Belbin et al., this meeting). Whilst genome-wide significance was not achieved in the initial study, we were able to use these data to identify correlative significant association, independent of the GWAS, for a variant that was a good candidate based upon previously detected association with gene expression and LOAD. Additional power for this study will be achieved by addition of the second population from Korcula.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2120870240