Summary Statistics of IGAP Age at onset survival GWAS dataset - Huang et al., 2017

A genome-wide survival analysis of 14,406 Alzheimer’s disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.

Acknowledgment statement for any data distributed by NIAGADS:

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), funded by the National Institute on Aging.

For investigators using Summary Statistics of IGAP Age at onset survival GWAS dataset data:

This work was supported by grants from the National Institutes of Health (U01AG049508, R01-AG035083 and RF-AG054011 (to A.M.G.) and R01-AG044546 and RF1AG053303 (to C.C.)), the JPB Foundation (to A.M.G.) and F Prime (to A.M.G.). Kuan-lin Huang received fellowship funding in part from the Ministry of Education in Taiwan and the Lucille P. Markey Special Emphasis Pathway in Human Pathobiology. Ke Hao is partially supported by the National Natural Science Foundation of China (Grant Nos. 21477087 and 91643201) and by the Ministry of Science and Technology of China (Grant No. 2016YFC0206507). For a detailed list of support for IGAP sample datasets please see Huang et al., 2017)

We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i–Select chips was funded by the French National Foundation on Alzheimer's disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer's Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01–AG–12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC–10–196728.

Summary Statistics of IGAP Age at onset survival GWAS dataset – Huang et al., 2017

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Acknowledgment statement for any data distributed by NIAGADS:

For investigators using Summary Statistics of IGAP Age at onset survival GWAS dataset data:

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