The ExomeChip ADC Northshore dataset was genotyped on the Illumina HumanExome BeadChip v1.0 at Northshore.
One variant rs75932628 (p.R47H) in TREM2 clustered poorly across all ADGC cohorts, and was therefore re-genotyped using a Taqman assay. Data on all samples underwent standard quality control procedures applied to genome-wide association studies (GWAS), including excluding variants with call rates <95%, and then filtering samples with call rate <95%. Variants with MAF>0.01 were evaluated for departure from HWE and any variants for PHWE<10-6 were excluded.
Population substructure within each of the five ExomeChip ADGC subsets (NorthShore, Miami, WashU, CHOP, and ADC7) was examined using PC analysis in EIGENSTRAT4, and population outliers (>6 SD) were excluded from further analyses; the first three PCs were adjusted for as covariates in association testing. Prior to analysis, the alternate and reference alleles were harmonized over all datasets. All sample genotyping and quality control was performed blind to participant’s disease status.
The exome chip data was first reported in the Sims et al. publication.
Detailed information about the dataset is provided in the following document: NG00079_ExomeChip_NS_README.txt
NACC Cases: 3776
NACC Controls: 2222
The US National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, and RC2 AG036528. Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank the contributors who collected samples used in this study, as well as the patients and their families, whose help and participation made this work possible. Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689-01).
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), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), 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), P50 AG016570 (PI Marie-Francoise Chesselet, MD, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD) , P30 AG028383 (PI Linda Van Eldik, 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), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD).