Back

A Specialized Reference Panel with Structural Variants Integration for Improving Genotype Imputation in Alzheimer's Disease and Related Dementias (ADRD)

Cheng, P.-L.; Wang, H.; Dombroski, B. A.; Farrell, J. J.; Horng, I.; Chung, T.; Tosto, G.; Kunkle, B. W.; Bush, W. S.; Vardarajan, B.; Schellenberg, G. D.; Lee, W.-P.

2024-07-23 genetic and genomic medicine
10.1101/2024.07.22.24310827 medRxiv
Show abstract

We developed an imputation panel for Alzheimers disease (AD) and related dementias (ADRD) using whole-genome sequencing (WGS) data from the Alzheimers Disease Sequencing Project (ADSP). Recognizing the significant associations between structural variants (SVs) and AD, and their underrepresentation in existing public reference panels, our panel uniquely integrates single nucleotide variants (SNVs), short insertions and deletions (indels), and SVs. This panel enhances the imputation of disease susceptibility, including rare AD-associated SNVs, indels, and SVs, onto genotype array data, offering a cost-effective alternative to whole-genome sequencing while significantly augmenting statistical power. Notably, we discovered 10 rare indels nominal significant related to AD that are absent in the TOPMed-r2 panel and identified three suggestive significant (p-value < 1E-05) AD-associated SVs in the genes EXOC3L2 and DMPK, were identified. These findings provide new insights into AD genetics and underscore the critical role of imputation panels in advancing our understanding of complex diseases like ADRD.

Published in Human Genetics and Genomics Advances (predicted rank #1) · training set

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

Human Genetics and Genomics Advances · published here
○ 84 papers in training set
Top 0.1%
18.2%
Similar papers in this journal
2
Nature Communications
○ 5641 papers in training set
Top 16%
11.7%
Similar papers in this journal
3
Genome Medicine
○ 183 papers in training set
Top 0.1%
10.9%
Similar papers in this journal
4
Genome Biology
○ 637 papers in training set
Top 2%
5.5%
Similar papers in this journal
5
Nature Genetics
○ 286 papers in training set
Top 1%
5.4%
Similar papers in this journal
50% of probability mass above
6
Alzheimer's & Dementia
177 papers in training set
Top 1%
4.8%
7
The American Journal of Human Genetics
○ 234 papers in training set
Top 1%
4.8%
8
npj Genomic Medicine
○ 36 papers in training set
Top 0.1%
4.0%
9
Cell Genomics
○ 172 papers in training set
Top 1%
3.2%
10
Genome Research
● 468 papers in training set
Top 3%
2.4%
11
Scientific Reports
○ 3612 papers in training set
Top 59%
1.4%
12
Journal of Genetics and Genomics
○ 38 papers in training set
Top 0.5%
1.1%
13
iScience
○ 1154 papers in training set
Top 28%
1.1%
14
Communications Biology
○ 993 papers in training set
Top 23%
1.1%
15
Nature Aging
○ 60 papers in training set
Top 1%
1.1%
16
Nature Biomedical Engineering
○ 47 papers in training set
Top 1%
1.1%
17
PLOS Genetics
● 862 papers in training set
Top 10%
1.0%
18
Human Genetics
○ 28 papers in training set
Top 0.5%
0.9%
19
Med
○ 39 papers in training set
Top 0.8%
0.8%
20
Human Genomics
○ 21 papers in training set
Top 0.5%
0.8%
21
Briefings in Bioinformatics
◐ 354 papers in training set
Top 7%
0.8%
22
eBioMedicine
○ 183 papers in training set
Top 7%
0.8%
23
Circulation: Genomic and Precision Medicine
○ 48 papers in training set
Top 0.9%
0.8%
24
Nature Medicine
○ 125 papers in training set
Top 4%
0.6%
25
Alzheimer's Research & Therapy
○ 57 papers in training set
Top 1%
0.6%
26
Genetics in Medicine Open
○ 11 papers in training set
Top 0.3%
0.6%
27
Nucleic Acids Research
◐ 1281 papers in training set
Top 15%
0.6%
28
Molecular Neurodegeneration
○ 55 papers in training set
Top 2%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.