Genome-wide analysis identified abundant genetic modulators of contributions of the apolipoprotein E alleles to Alzheimer's disease risk.

The apolipoprotein E (APOE) ε2 and ε4 alleles have beneficial and adverse impacts on Alzheimer's disease (AD), respectively, with incomplete penetrance, which may be modulated by other genetic variants.We examined whether the associations of the APOE alleles with other polymorphisms in the genome can be sensitive to AD-affection status.We identified associations of the ε2 and ε4 alleles with 314 and 232 polymorphisms, respectively. Of them, 35 and 31 polymorphisms had significantly different effects in AD-affected and -unaffected groups, suggesting their potential involvement in the AD pathogenesis by modulating the effects of the ε2 and ε4 alleles, respectively. Our survival-type analysis of the AD risk supported modulating roles of multiple group-specific polymorphisms. Our functional analysis identified gene enrichment in multiple immune-related biological processes, for example, B cell function.These findings suggest involvement of local and inter-chromosomal modulators of the effects of the APOE alleles on the AD risk.

Duke Scholars

Author Yury Loika  

Author Irina Kulminskaya  

Author Alexander Kulminski Social Science Research Institute