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P2‐125: METABOLIC AND COGNITIVE EFFECTS OF A WESTERN DIET ON APOE4 MICE
Author(s) -
Jones Nahdia S.,
Rebeck G. William
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2532
Subject(s) - endocrinology , medicine , adipose tissue , population , genetically modified mouse , obesity , biology , transgene , biochemistry , environmental health , gene
1,008 controls and were analyzed by Affymetrix SNP6.0 array. We excluded SNPs that (i) had low call rates (<98%), (ii) were located on sex chromosomes, (iii) deviated from Hardy-Weinberg equilibrium in the controls (p < 1.0310) and (iv) had low minor allele frequency <0.01. We then applied the following QC criteria to exclude samples: (i) samples for which <98% of the genotypes were called and (ii) samples in the same family according to pihat (>0.4). Furthermore, EIGENSTRATand fastSTRUCTURE analyses were performed to remove outliers. Results: We calculated PRS and PHS for each sample. We found that a model combined PRS and APOE effects had more higher discrimination ability than that with only APOE effects. We examined whether SNPs associated with the other diseases contribute to AD discrimination. Consequently, we identified that SNPs associated with schizophrenia or major depressive disorder showed significant AD discrimination, suggesting that the genetic factors of psychiatric diseases overlap with them of AD. On the other hand, SNPs associated with non-psychiatric diseases did not show significant AD discrimination. Finally, we examined relationship between PHS and the age at onset of patients. PHS showed significant negative correlation with the age at onset of patients. Analysis using only ApoEε4 non-carrier also showed significant difference between the high-PHS group and the low-PHS group, suggesting that polygenic effects influence the age at onset of patients without ApoEε4. Conclusions: We proved that PRS and PHS worked effectively in Japanese population.