Transcriptomics

Dataset Information

14

Genome-wide survey of large rare copy number variations in Alzheimer’s disease among Caribbean Hispanics


ABSTRACT: 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. Case-control analysis, screening of large copy number variation in 559 Alzheimer cases and 554 control subjects of Caribbean Hispanic ancestry

ORGANISM(S): Homo sapiens  

SUBMITTER: Stephen W Scherer   Mahdi Ghani  Dalila Pinto  Danielle Moreno  Yakov Grinberg  Peter St George-Hyslop  Christine Sato  Joseph H Lee  Richard Mayeux  Ekaterina Rogaeva 

PROVIDER: E-GEOD-33528 | ArrayExpress | 2012-04-30

SECONDARY ACCESSION(S): GSE33528PRJNA148797

REPOSITORIES: GEO, ArrayExpress

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Publications

Genome-wide survey of large rare copy number variants in Alzheimer's disease among Caribbean hispanics.

Ghani Mahdi M   Pinto Dalila D   Lee Joseph H JH   Grinberg Yakov Y   Sato Christine C   Moreno Danielle D   Scherer Stephen W SW   Mayeux Richard R   St George-Hyslop Peter P   Rogaeva Ekaterina E  

G3 (Bethesda, Md.) 20120101 1


Recently genome-wide association studies have identified significant association between Alzheimer's disease (AD) 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 variation (CNV) in a dataset of Caribbean Hispanic origin (554 controls and 559 AD cases that were previously investigated in a SNP-based genome-wide association study using  ...[more]

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