期刊
PLOS GENETICS
卷 13, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1007045
关键词
-
资金
- National Institutes of Health [R01-AG044546, P01-AG003991, RF1AG053303]
- Alzheimer Association [NIRG-11-200110, BAND-14-338165, BEG-15-362540]
- JPB Foundation
- NIH [P50-AG05681, P01-AG03991, P01-AG026276]
- National Institute on Aging (NIA) [U24-AG21886, R01AG023629, R01AG15928, R01AG20098]
- National Institute on Aging [U24 AG026395]
- NIA [U01 AG032984, R01 AG033193, U24AG021886, U01AG016976, U24AG041689]
- National Heart, Lung, and Blood Institute (NHLBI)
- NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
- Austrian Stroke Prevention Study (ASPS)
- Cardiovascular Health Study (CHS)
- Erasmus Rucphen Family Study (ERF)
- Framingham Heart Study (FHS)
- Rotterdam Study (RS)
- National Heart, Lung, and Blood Institute (NHLBI) [U01HL080295, U01HL130114]
- Human Genome Sequencing Center at the Baylor College of Medicine [U54 HG003273]
- Broad Institute Genome Center [U54HG003067]
- Washington University Genome Institute [U54HG003079]
- NIA
- NIH
- National Institutes of health, National Library of Medicine
- [UF1AG047133]
- [U01AG049505]
- [U01AG049506]
- [U01AG049507]
- [U01AG049508]
- [U01AG052411]
- [U01AG052410]
- [U54AG052427]
- [5RC2HL102419]
- [HL105756]
- [HHSN268201200036C]
- [HHSN268200800007C]
- [N01HC55222]
- [N01HC85079]
- [N01HC85080]
- [N01HC85081]
- [N01HC85082]
- [N01HC85083]
- [N01HC85086]
Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据