Novel risk loci and pathways associated with Alzheimer disease in African Americans: A GWAS and meta-analysis summary statistics- Kunkle et al. (2020)

Overview

A GWAS meta-analysis of 2,784 cases and 5,222 controls recruited from several case-control and family-based studies of African Americans was performed. A detailed description of the original cohorts and summary demographics of all samples included in this analysis are provided in the Supplementary Material of Kunkle et al. (Supplementary Note; Supplementary Tables 1-3). Imputation was performed with the African Genome Resources (AGR) panel (https://www.apcdr.org/data/),The final SNP set for analysis included 29,610,185 genotyped and imputed variants. Genotype dosages were analyzed within each dataset and subsequently meta-analyzed, adjusting for age, sex and PCs for population substructure (Model 1), and subsequently in addition for APOE genotype (Model 2). Additional details on these analyses and the methods for gene, pathway and expression association analyses can be found in the Supplementary Material of Kunkle et al.

Two datasets are provided.
The first one corresponds to the meta-analysis results obtained from model 1 (age, sex, and age adjusted) including genotyped and imputed data (African Genome Resources (AGR) panel (https://www.apcdr.org/data/) of 2,784 Alzheimer’s disease cases and cases and 5,222 cognitively normal controls.
The second one corresponds to the meta-analysis results of the same dataset and imputation, including adjustment for APOE in the model (model 2).

Each data file consists of information on SNP and its association to Alzheimer's disease based on meta-analysis in the publication mentioned below. Although the individual datasets examined excluded any SNPs with call rates <95%, ADGC meta-analysis only analyzed SNPs either genotyped or successfully imputed in at least 30% of the AD cases and 30% of the control samples across all datasets. Please see the Supplementary methods for further details on quality control steps performed.

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

ADGC is releasing the summary results data from this analysis in order to enable other researchers to examine particular variants or loci for their evidence of association. We welcome your request with the proviso that these summary data should not be used for research into the genetics of intelligence, education, social outcomes such as income, or potentially sensitive behavioral traits such as alcohol or drug addictions.

Disease

Submission date:

8/20/2020

PI Information

Brian Kunkle

University of Miami

Christiane Reitz

Columbia University

Acknowledgment/Funding Sources

The Kunkle et al. ADGC African American GWAS meta-analysis was supported by NIH grants: RF1 AG054023, U24 AG056270, ADGC - U01 AG032984, NIA-LOAD – U24 AG026395, U24 AG026390 (PI Richard Mayeux, MD), NIAGADS – U24 AG041689 (PI Li-San Wang, PhD), WHICAP – R01 AG037212, R37 AG015473 (PI Richard Mayeux, MD), NCRAD - U24 AG021886 (PI Tatiana Foroud, PhD), Indianapolis AA – R01 AG009956, RC2 AG036650 (PI Kathleen Hall, PhD), ACT – U01 AG06781, U01 HG004610 (PI Eric Larson, MD, MPH), MIRAGE – R01 AG009029 (PI Lindsay Farrer, PhD), GenerAAtions – 5R01 AG20688 (PI M. Daniele Fallin, PhD), Pittsburg – P50 AG005133 (PI O. Lopez), AG030653, AG041718, AG064877 (PI M. Ilyas Kamboh, PhD), Case Western Reserve University – R01 AG019085 (PI Jonathan Haines, PhD), CHAP – R01 AG11101, R01 AG030146, RC2 AG036650 (PI Denis Evans, MD), ROS/MAP - P30 AG10161, R01 AG15819, R01 AG30146, R01 AG17917, R01 AG15819 (PI David Bennett, MD), African-American AD Genetics Study – R01 AG028786 (PI Jennifer Manly, PhD), MARS/CORE – R01 AG22018, P30 AG10161 (PI Lisa Barnes, PhD), Mayo – P50 AG0016574, R01 032990, KL2 RR024151 (PIs Ronald C. Petersen, MD, PhD, Nilufer Ertekin-Taner, MD, PhD and Neill Graff-Radford, MD), Miami – R01 AG027944, R01 AG028786 (PI Margaret Pericak-Vance, PhD), Wake Forest (PI Goldie Byrd, PhD), MSSM (PI Joseph Buxbaum, PhD) and MSSM – P50 AG05681, P01 AG03991, P01 AG026276 (PI Alison Goate). CR was further supported by NIH grants (RF1AG054080, U01AG052410, AG0087202). The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), AG045058 (PI Thomas Obisesan, MD, MPH), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John C. Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

Data Use Limitations

NG00100 - Novel risk loci and pathways associated with Alzheimer disease in African Americans: A GWAS and meta-analysis summary statistics- Kunkle et al. (2020)

Summary Statistics p-values only

Molecular Data Type

Type

Disease