rs4295

This study investigated associations between 15 SNPs and one insertion/deletion polymorphism in the ACE gene region with coping styles in 541 healthy adults and 194 depressed patients. The strongest association was rs8066276 (intronic SNP) with the Distraction coping factor (adjusted P=0.009, Cohen's f=0.10) in healthy subjects, where T-allele carriers showed significantly lower Distraction scores. rs4305 showed significant association with Devaluation/Defense coping (adjusted P=0.02, f=0.15). These and other ACE polymorphisms were associated with positive (stress-reducing) coping styles in both samples, suggesting the ACE gene is involved in development of adaptive coping strategies.

Association analysis of Alzheimer disease candidate genes in 738 families (4704 individuals) and 296 cases/566 controls detected significant haplotype effects in ACE gene (p=0.0004 family, p=0.029 case-control) and putative multilocus associations between ACE, A2M, and LRRTM3 (p<0.001 MDR-PDT). ACE ancestral haplotypes show consistent replication across independent samples with attributable risk explaining ~8-16% of LOAD cases.

This paper presents a two-stage analysis approach to identify genetic heterogeneity and gene-gene interactions in late-onset Alzheimer disease (LOAD). Using Bayesian Classification clustering followed by multifactor dimensionality reduction (MDR), the authors identified LRRTM3 as a primary stratification gene and found that markers in PLAU, ACE, and CDC2 were associated with LOAD specifically within distinct LRRTM3-defined subgroups, suggesting complex gene-gene interactions in LOAD etiology.