Genome-wide summary statistics for cognitively defined late-onset Alzheimer’s disease subgroups

Overview

GWAS meta-analysis summary statistics for case-control analyses of five cognitively defined Alzheimer’s disease subgroups.
1. Controls vs. memory predominant AD
2. Controls vs. visuospatial predominant AD
3. Controls vs. language predominant AD
4. Controls vs. no domain with substantial relative impairment AD group
5. Controls vs. multiple substantial relative impairment AD group

The subgroups were assigned on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. The executive functioning prominent AD subgroup was too small to analyze and was left out.

The individual GWAS sets were based on 1000G imputed data (March 2012 build) and were adjusted for age, sex, and principal components and finally meta-analyzed using METAL. The studies used for meta-analysis were the Adult Changes in Thought (ACT) study, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Religious Orders Study (ROS), the Memory and Aging Project (MAP), and the University Of Pittsburgh (PITT) study. The GWAS summary statistics files were quality controlled to exclude SNPs with minor allele frequency < 3%, monomorphic SNPs.

The p-value data is generally available to all users using the link below; however, gaining access to the complete dataset requires a formal data request.

Disease

Submission date:

12/19/2018

Samples

Each cell represents controls/cases in respective subgroup

Mem - memory predominant AD subgroup
Vsp - visuospatial predominant AD subgroup
Lan - language predominant AD subgroup
None - no domain with substantial relative impairment AD subgroup
Mixed - multiple substantial relative impairment AD subgroup

	Mem	Vsp	Lan	None	Mixed
ACT	1407/75	1407/61	1407/38	1407/241	X
ADNI	325/180	325/77	325/47	325/265	325/25
ROS/MAP	887/111	887/80	887/167	887/243	887/69
PITT	825/287	825/76	825/72	825/225	825/47
TOTAL	3444/653	3444/294	3444/324	3444/974	3444/141

PI Information

Paul Crane

Acknowledgment/Funding Sources

Analyses were funded by R01 AG042437 (P Crane, PI) and R01 AG029672 (P Crane, PI).

Data archiving was supported by R01 AG042437-S1 (P Crane, PI)

Dr. Mez’s efforts were also supported by K23 AG046377 (J Mez, PI)

The efforts of Dr. Gibbons, Dr. Grabowski, and Dr. Keene were also supported by P50 AG005136 (T Grabowski, PI). Dr. Keene’s efforts were also supported by the Nancy and Buster Alvord Endowment.

Dr. Gross’s efforts were supported by K01 AG050699 (A Gross, PI).

Dr. Bird’s efforts were supported by Department of Veterans Affairs Research Funds.

Dr. Saykin’s efforts were supported by U01 AG042904 (M Weiner, PI), P30 AG010133 (A Saykin, PI), and R01 AG019771 (A Saykin, PI).

ACT data collection was supported by U01 AG006781 (E Larson and P Crane, MPIs). ACT genotyping was supported by U01 HG006375 (E Larson and G Jarvik, MPIs). Cerebellum samples for genotyping for some ACT samples were prepared with support from P50 AG005136 (T Grabowski, PI). The authors thank Aimee Schantz and Allison Beller for administrative support for the ACT cerebellum samples.

ADNI data collection and genotyping were supported by U01 AG024904 (M Weiner, PI). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

MAP data collection and genotyping were supported by R01 AG017917 (D Bennett, PI). Additional genotyping was supported by Kronos, Zinfandel, and U01 AG032984 (G Schellenberg, PI).

ROS data collection and genotyping were supported by P30 AG10161 (D Bennett, PI), R01 AG15819 (D Bennett, PI), and R01 AG30146 (D Evans, PI). Additional genotyping was supported by Kronos, Zinfandel, and U01 AG032984 (G Schellenberg, PI).

PITT data collection were funded by P50 AG05133 (O Lopez PI), R01 AG030653 (MI Kamboh, PI), and R01 AG041718 (MI Kamboh, PI).

Data Use Limitations

NG00073 - Genome-wide summary statistics for cognitively defined late-onset Alzheimer’s disease subgroups

Summary Statistics p-values only

Molecular Data Type

Type

Disease