Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database

被引:1367
作者
Bertram, Lars [1 ]
McQueen, Matthew B.
Mullin, Kristina
Blacker, Deborah
Tanzi, Rudolph E.
机构
[1] Massachusetts Gen Hosp, Dept Neurol, MIND, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[3] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA
[4] Massachusetts Gen Hosp, Gerontol Res Unit, Dept Psychiat, Charlestown, MA 02129 USA
关键词
D O I
10.1038/ng1934
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses for each polymorphism with available genotype data in at least three case-control samples. In addition to identifying the epsilon 4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11 - 1.38 for risk alleles and 0.92 - 0.67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases.
引用
收藏
页码:17 / 23
页数:7
相关论文
共 30 条
  • [1] The polymorphism in exon 3 of the low density lipoprotein receptor-related protein gene is weakly associated with Alzheimer's disease
    Beffert, U
    Arguin, C
    Poirier, J
    [J]. NEUROSCIENCE LETTERS, 1999, 259 (01) : 29 - 32
  • [2] Alzheimer's disease: one disorder, too many genes?
    Bertram, L
    Tanzi, RE
    [J]. HUMAN MOLECULAR GENETICS, 2004, 13 : R135 - R141
  • [3] Genomic Epidemiqlogy of complex disease: The need for an electronic evidence-based approach to research synthesis
    Bracken, MB
    [J]. AMERICAN JOURNAL OF EPIDEMIOLOGY, 2005, 162 (04) : 297 - 301
  • [4] Problems of reporting genetic associations with complex outcomes
    Colhoun, HM
    McKeigue, PM
    Smith, GD
    [J]. LANCET, 2003, 361 (9360) : 865 - 872
  • [5] DELBO R, 2006, NEUROBIOL AGING, V27
  • [6] METAANALYSIS IN CLINICAL-TRIALS
    DERSIMONIAN, R
    LAIRD, N
    [J]. CONTROLLED CLINICAL TRIALS, 1986, 7 (03): : 177 - 188
  • [7] Bias in meta-analysis detected by a simple, graphical test
    Egger, M
    Smith, GD
    Schneider, M
    Minder, C
    [J]. BMJ-BRITISH MEDICAL JOURNAL, 1997, 315 (7109): : 629 - 634
  • [8] Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease - A meta-analysis
    Farrer, LA
    Cupples, LA
    Haines, JL
    Hyman, B
    Kukull, WA
    Mayeux, R
    Myers, RH
    PericakVance, MA
    Risch, N
    vanDuijn, CM
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 278 (16): : 1349 - 1356
  • [9] A comprehensive review of genetic association studies
    Hirschhorn, JN
    Lohmueller, K
    Byrne, E
    Hirschhorn, K
    [J]. GENETICS IN MEDICINE, 2002, 4 (02) : 45 - 61
  • [10] 'Racial' differences in genetic effects for complex diseases
    Ioannidis, JPA
    Ntzani, EE
    Trikalinos, TA
    [J]. NATURE GENETICS, 2004, 36 (12) : 1312 - 1318