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Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer’s disease

Overview of attention for article published in BMC Medical Genomics, May 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (64th percentile)

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1 news outlet
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1 tweeter

Citations

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18 Dimensions

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36 Mendeley
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Title
Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer’s disease
Published in
BMC Medical Genomics, May 2017
DOI 10.1186/s12920-017-0267-0
Pubmed ID
Authors

Kwangsik Nho, Sungeun Kim, Emrin Horgusluoglu, Shannon L. Risacher, Li Shen, Dokyoon Kim, Seunggeun Lee, Tatiana Foroud, Leslie M. Shaw, John Q. Trojanowski, Paul S. Aisen, Ronald C. Petersen, Clifford R. Jack, Michael W. Weiner, Robert C. Green, Arthur W. Toga, Andrew J. Saykin

Abstract

The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sequence data from 757 non-Hispanic Caucasian participants was used in the present analysis. We extracted all rare variants (MAF (minor allele frequency) < 0.05) within a 312 kb window in APOE's vicinity encompassing 12 genes. We assessed CSF and neuroimaging (MRI and PET) biomarkers as LOAD-related quantitative endophenotypes. Gene-based analyses of rare variants were performed using the optimal Sequence Kernel Association Test (SKAT-O). A total of 3,334 rare variants (MAF < 0.05) were found within the APOE region. Among them, 72 rare non-synonymous variants were observed. Eight genes spanning the APOE region were significantly associated with CSF Aβ1-42 (p < 1.0 × 10(-3)). After controlling for APOE genotype and adjusting for multiple comparisons, 4 genes (CBLC, BCAM, APOE, and RELB) remained significant. Whole-brain surface-based analysis identified highly significant clusters associated with rare variants of CBLC in the temporal lobe region including the entorhinal cortex, as well as frontal lobe regions. Whole-brain voxel-wise analysis of amyloid PET identified significant clusters in the bilateral frontal and parietal lobes showing associations of rare variants of RELB with cortical amyloid burden. Rare variants within genes spanning the APOE region are significantly associated with LOAD-related CSF Aβ1-42 and neuroimaging biomarkers after adjusting for APOE genotype. These findings warrant further investigation and illustrate the role of next generation sequencing and quantitative endophenotypes in assessing rare variants which may help explain missing heritability in AD and other complex diseases.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 25%
Other 7 19%
Researcher 3 8%
Student > Master 2 6%
Student > Bachelor 2 6%
Other 4 11%
Unknown 9 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 22%
Neuroscience 5 14%
Medicine and Dentistry 4 11%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Psychology 2 6%
Other 2 6%
Unknown 13 36%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 August 2018.
All research outputs
#1,610,525
of 13,322,622 outputs
Outputs from BMC Medical Genomics
#82
of 671 outputs
Outputs of similar age
#49,367
of 267,838 outputs
Outputs of similar age from BMC Medical Genomics
#5
of 14 outputs
Altmetric has tracked 13,322,622 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 671 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,838 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.