The genome-wide survival association study was performed on 14,406 AD case samples and 25,849 control samples from the International Genomics of Alzheimer’s Project (IGAP) consortium (see Table 1a, Huang et al., 2017 for details). The final IGAP meta-analysis dataset consists of samples from the Alzheimer’s Disease Genetics Consortium (ADGC), Genetic and Environmental Risk in Alzheimer’s Disease (GERAD), European Alzheimer’s Disease Initiative (EADI), and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). The study cohorts consist of case–control and longitudinal cohorts and are described in detail in online methods of (Huang et al., 2017). 8,253,925 imputed and genotyped SNPs passed quality control and were included for meta-analysis across all cohorts. There was no evidence of genomic inflation (λ = 1.026).
Four loci showed genome-wide significant associations with AAOS: BIN1 (P = 3.9x10−10), MS4A (P = 2.3x10−9), PICALM (P = 9.1x10−12) and APOE (P = 7.8x10−52)). Four other AD risk loci previously reported in the IGAP GWAS showed associations that reached suggestive significance: CR1 (P = 1.2x10−6), SPI1 (previously labeled as CELF1 in the 2013 IGAP GWAS paper1; P = 8.4x10−6), SORL1 (P = 5.5x10−6) and FERMT2 (P = 2.3x10−6). We also identified 14 loci that reached suggestive significance in the survival analysis, three of which (rs116341973, rs1625716 and rs11074412) were nominally associated with AD risk.
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.
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.