GENDER DIFFERENCES IN MEMORY-RELATED FUNCTIONAL CONNECTIVITY IN AGING AND GENETIC RISK FOR AD

Abstract

analyzed, and the method employed (Table 1). Gene pathway and network enrichment analyses were performed on the genetic findings to get a better understanding of these findings. Results: The number of ADNI genetic association publications in 2013 is 50, in which 20 papers used only APOE, and 30 papers used the GWAS and sequencing data. Among all these papers, multiple types of AD related phenotypes including clinical status, structural and functional neuroimaging, fluid biomarkers, and neuropsychological assessment, were employed as qualitative or quantitative traits to find novel risk genetic variants. Table 1 shows the classification of papers based on various genotype, phenotype, and method applied. Besides the previously known top 10 AD genes, 26 additional genetic association findings were identified by different approaches. For example, 11 new susceptible loci were reported by a large-scale meta-analytical GWAS [1] and SPON1 was discovered by two independent studies [2-3]. Enrichment analyses of thesemajor findings identified 6 immune response pathways (p<0.01), three development pathways (p<0.006), and an inflammation process network (p1⁄47.7e-5). Conclusions: Genetic studies of multidimensional ADNI phenotypes continue to confirm known AD genetic risk factors and discover novel susceptibility loci. With the recent release of ADNI whole genome sequencing data, we expect to see future studies addressing not only common variants but also rare variants, and identifying functional variants instead of tag SNP associations. Reference [1] Lambert et al., Nature Genetics, 2013, 45(12):1452-8. [2] Jahanshada et al., Proc Natl Acad Sci USA, 2013, 110(12):4768-73. [3] Sherva, et al., Alzheimers Dement, 2014, 10(1):45-52.