@article{20c005f2361042259cb3f377dd594858,
title = "A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease",
abstract = "Introduction: The genetic architecture of Alzheimer's disease (AD) is only partially understood. Methods: We conducted an association study for AD using whole sequence data from 507 genetically enriched AD cases (i.e., cases having close relatives affected by AD) and 4917 cognitively healthy controls of European ancestry (EA) and 172 enriched cases and 179 controls of Caribbean Hispanic ancestry. Confirmation of top findings from stage 1 was sought in two family-based genome-wide association study data sets and in a whole genome–sequencing data set comprising members from 42 EA and 115 Caribbean Hispanic families. Results: We identified associations in EAs with variants in 12 novel loci. The most robust finding is a rare CASP7 missense variant (rs116437863; P = 2.44 × 10−10) which improved when combined with results from stage 2 data sets (P = 1.92 × 10−10). Discussion: Our study demonstrated that an enriched case design can strengthen genetic signals, thus allowing detection of associations that would otherwise be missed in a traditional case-control study.",
keywords = "Association study, Enriched case-control, Gene-based analyses, Genome-wide association studies, Whole exome sequencing",
author = "{Alzheimer's Disease Sequencing Project} and Xiaoling Zhang and Congcong Zhu and Gary Beecham and Vardarajan, {Badri N.} and Yiyi Ma and Daniel Lancour and Farrell, {John J.} and Jaeyoon Chung and Michelle Bellair and Huyen Dinh and Harsha Doddapeneni and Shannon Dugan-Perez and Adam English and Gibbs, {Richard A.} and Yi Han and Jianhong Hu and Joy Jayaseelan and Divya Kalra and Ziad Khan and Viktoriya Korchina and Sandra Lee and Yue Liu and Xiuping Liu and Donna Muzny and Waleed Nasser and William Salerno and Jireh Santibanez and Evette Skinner and Simon White and Kim Worley and Yiming Zhu and Alexa Beiser and Yuning Chen and Cupples, {L. Adrienne} and Anita DeStefano and Josee Dupuis and John Farrell and Lindsay Farrer and Honghuang Lin and Liu, {Ching Ti} and Kathy Lunetta and Devanshi Patel and Chloe Sarnowski and Claudia Satizabal and Sudha Seshadri and Sun, {Fangui Jenny} and Choi, {Seung Hoan} and Eric Banks and Stacey Gabriel and Xia, {Li Charlie}",
note = "Funding Information: This work was supported in part by NIA grants R01AG048927, P30-AG13846, and RF1AG057519. The Alzheimer's Disease Sequencing Project (ADSP) is comprised of two Alzheimer's disease genetics consortia and three National Human Genome Research Institute (NHGRI) funded Large Scale Sequencing and Analysis Centers (LSAC). The two AD genetics consortia are the Alzheimer's Disease Genetics Consortium (ADGC) funded by the National Institute on Aging (NIA) grant U01-AG032984 and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) funded by NIA (R01 AG033193), the National Heart, Lung, and Blood Institute (NHLBI), and other National Institute of Health (NIH) institutes and foreign governmental and nongovernmental organizations. The discovery phase analysis of sequence data is supported through UF1-AG047133 (Drs. J.J.F, J.L.H., R.M., M.A.P.-V., and G.D.S.); U01-AG049505 to Dr. Sudha Seshadri; U01-AG049506 to Dr. Eric Boerwinkle; U01-AG049507 to Dr. Ellen Wijsman; and U01-AG049508 to Dr. Alison Goate) and the Discovery Extension Phase analysis is supported through U01-AG052411 to Dr. Goate, U01-AG052410 to Dr. Pericak-Vance, and U01-AG052409 to Drs. Seshadri and Myriam Fornage. Data generation and harmonization in the follow-up phases are supported by U54-AG052427 to Drs. Schellenberg and Li-San Wang. The authors thank the investigators who assembled and characterized participants of cohorts included in this study: Funding Information: This work was supported in part by NIA grants R01AG048927 , P30-AG13846 , and RF1AG057519 . The Alzheimer's Disease Sequencing Project (ADSP) is comprised of two Alzheimer's disease genetics consortia and three National Human Genome Research Institute (NHGRI) funded Large Scale Sequencing and Analysis Centers (LSAC). The two AD genetics consortia are the Alzheimer's Disease Genetics Consortium (ADGC) funded by the National Institute on Aging ( NIA) grant U01-AG032984 and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) funded by NIA ( R01 AG033193 ), the National Heart, Lung, and Blood Institute (NHLBI), and other National Institute of Health (NIH) institutes and foreign governmental and nongovernmental organizations. The discovery phase analysis of sequence data is supported through UF1-AG047133 (Drs. J.J.F, J.L.H., R.M., M.A.P.-V., and G.D.S.); U01-AG049505 to Dr. Sudha Seshadri; U01-AG049506 to Dr. Eric Boerwinkle; U01-AG049507 to Dr. Ellen Wijsman; and U01-AG049508 to Dr. Alison Goate) and the Discovery Extension Phase analysis is supported through U01-AG052411 to Dr. Goate, U01-AG052410 to Dr. Pericak-Vance, and U01-AG052409 to Drs. Seshadri and Myriam Fornage. Data generation and harmonization in the follow-up phases are supported by U54-AG052427 to Drs. Schellenberg and Li-San Wang. The authors thank the investigators who assembled and characterized participants of cohorts included in this study: Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2019",
month = mar,
doi = "10.1016/j.jalz.2018.10.005",
language = "English (US)",
volume = "15",
pages = "441--452",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "3",
}
