NSAID-LIV
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010001422 | EGA |
REPOSITORIES: EGA
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2014-04-21 | GSE48350 | GEO
Project description:Recently genome-wide association studies have identified significant association between Alzheimer’s disease and variations in CLU, PICALM, BIN1, CR1, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7. However, the pathogenic variants in these loci have not yet been found. We conducted a genome-wide scan for large copy number variations (CNVs) in a dataset of Caribbean Hispanic origin (554 controls and 559 cases with late-onset Alzheimer’s disease) that was previously investigated in a SNP-based genome-wide association study using Illumina HumanHap 650Y platform. We ran four CNV calling algorithms and analyzed rare large CNVs (>100 Kb) to obtain high-confidence calls that were detected by at least two algorithms. In total, 734 such CNVs were observed in our dataset. Global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications, total or average CNV size; and number of genes affected by CNVs. However, we observed a nominal association between Alzheimer’s disease and a ~470 Kb duplication on chromosome15q11.2 (P=0.037). This duplication, encompassing up to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1 and WHAMML1) was present in 10 cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes was further confirmed by quantitative PCR. The current study did not detect CNVs (including common CNVs) that affect novel Alzheimer’s disease loci reported by large genome-wide association studies. However, since the array technology used in our study has limitations in detecting small CNVs, future studies must carefully assess novel AD associated genes for the presence of disease related CNVs.
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Project description:1000Genomes imputed data set of 581 cases and 417 controls for male-pattern baldness
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Project description:Genome wide DNA methylation profiles of various human brain regions (cerebellum, occipital lobe, etc). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. The dataset includes 130 samples. Multiple brain regions were assessed per subject. The goal was to evaluate the effect of HIV infection on DNA methylation levels. Genome wide DNA methylation profiles of various brain regions from HIV positive and negative subjects. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. Dataset included 130 samples: 99 samples from HIV+ subjects and 31 samples from HIV- subjects. The Illumina Infinium450 platform was applied to various brain regions from HIV+ and HIV- subjects. We evaluated 130 brain samples from 84 different subjects. Specifically, we considered cerebellum (20 HIV+ samples and 4 controls), frontal lobe (2 cases, 4 controls), hippocampus (4 controls), medial frontal cortex (18 cases), occipital cortex (59 cases, 13 controls), temporal cortex (4 controls). In total, there were 99 samples from HIV+ subjects and 31 samples from HIV- controls of similar ages. The subjects were recruited from the National Neurological AIDS Bank study or Multicenter AIDS Cohort study in Los Angeles. Informed consent and all study procedures were approved by the UCLA Medical IRB. DNAm data from HIV+ cases and HIV- controls were generated at the same time and randomized across plates and chips. HIV viral load information was available for blood (measured at the last blood draw) and for cerebrospinal fluid (CSF).
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