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IC‐P‐144: Targeted lipidomic‐pathway–guided genetic association with Alzheimer's disease–relevant endophenotypes
Author(s) -
Kim Sungeun,
Nho Kwangsik,
Shen Li,
Kling Mitchel,
Han Xianlin,
Zhu Hongjie,
Sullivan Patrick,
Arnold Steven,
Risacher Shan,
Ramanan Vijay,
Doraiswamy P. Murali,
Trojanowski John,
KaddurahDaouk Rima,
Saykin Andrew
Publication year - 2013
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.2013.05.141
Subject(s) - endophenotype , alzheimer's disease neuroimaging initiative , sphingolipid , apolipoprotein e , lipidomics , biology , medicine , alzheimer's disease , endocrinology , neuroscience , genetics , disease , bioinformatics , cognition
analyses were performed using a dominant genetic model with translocator protein (18-kDa) (TSPO) genotype, age at PET scan, gender, and education as covariates. Association was tested with/without APOE e 4 status as a covariate. P-values were corrected for multiple testing using 10,000 permutations. The influence of the gene was further investigated using haplotypes estimated from a set of independent and significant SNPs from the genelevel analysis. Results: Four independent and significant SNPs (rs12567614, rs8679, rs9282580, rs892348) were associated with mean [11 C]PBR28 uptake in cingulate cortex in the gene-level analysis. When these were combined in the haplotype analysis, two haplotypes (TACG and CGTC) were associated with mean cingulate PBR at uncorrected p<0.05, but in the opposite directions (Figure 1). One association (CGTC) was significant after multiple testing correction (corrected p<0.05) (Table 2) although the association of PARP1 gene showedmarginal significance (p<0.079) after correcting for APOE e 4 status. Conclusions: