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P3‐012: Circular RNA (circRNA‐7; ciRS‐7) impacts microrna‐7 trafficking and downregulates the ubiquitin‐conjugating enzyme E2A (UBE2A) in sporadic Alzheimer's disease (AD) brain
Author(s) -
Lukiw Walter J.,
Zhao Yuhai,
Pogue Aileen I.,
Bhattacharjee Surjyadipta,
Dua Prerna
Publication year - 2015
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.2015.06.878
Subject(s) - circular rna , biology , microrna , non coding rna , rna , gene , mirbase , human brain , genetics , microbiology and biotechnology , neuroscience
especially in African-origin populations at risk for AD. Here we report a genome-wide association study (GWAS) of HCY in this population. Methods: Quality-controlled cross-sectional plasma HCY and GWAS data were obtained from 1858 participants (898 African-Americans in Indianapolis, Indiana, USA (IND) and 960 Yoruba in Ibadan, Nigeria (YOR); Table 1) from the Indianapolis-Ibadan Dementia Project cohort. Genotyping was performed using the Illumina Omni1-Quad for IND and Omni2.5M for YOR. Standard QC and imputation to 1000 Genome reference panel were performed prior to combining both data sets. Analysis was conducted using an additive genetic model with sex, age at the time of HCYmeasure, plasma vitamin B12 level, the first eigenvector from GWAS data and dementia status as covariates. SNPs with p<5x10were considered to be genome-wide significant. Results:One SNP (rs6940729, p1⁄44.71x10) in the CD2-associated protein (CD2AP) gene was genome-wide significantly associated with HCY level. Additional suggestive signals (p<1x10) included SNPs near DYNC1I1, CCDC82, BIRC8, and DTWD2 genes. Conclusions: This is the first study showing the relationship of CD2AP with plasma homocysteine. CD2AP may influence neuronal cells by mediating cell adhesion and cytoskeletal structure directly or via influence on HCY. Other suggestive signals near genes associated with obesity, Parkinson disease and chronic myeloid leukemia warrant further study. References: 1. Seshadri et al., N Engl J Med, 2002. 2. Rajagopalan et al., Neuroreport, 2011. 3. Siva et al., QJM, 2007. 4. Hendrie et al., Int Psychogeriatr, 2013. 5. Loureiro et al. Int J Dev Neurosci. 2008. 6. Shulman et al. Hum Mol Genet. 2013.