Premium
P1‐253: Support for Genetic Association between Variants in PPP3R1 and MAPT and Rate of Progression of Alzheimer's Disease
Author(s) -
Peterson David,
Kauwe John,
Crowley Jared,
Corcoran Christopher,
Cruchaga Carlos,
Goate Alison,
Norton Maria,
Green Robert,
Munger Ron,
Breitner John,
WelshBohmer Kathleen,
Lyketsos Kostas,
Tschanz JoAnn
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.533
Subject(s) - clinical dementia rating , tau protein , oncology , dementia , single nucleotide polymorphism , disease , alzheimer's disease , medicine , genetic association , population , genetics , gene , biology , genotype , environmental health
combined analyses of cases and controls.Results: In the case+controls analyses, CLU rs11136000 was significantly associated with better scores for multiple phenotypes from Logical Memory, namely LMDR (b 1⁄4 0.94, p 1⁄4 0.0042), LMPR (b1⁄4 2.74, p1⁄4 0.01) and LMIR (b1⁄4 0.69, p1⁄4 0.03). Similar results for CLU were obtained in controls-only analyses, where LMDR (b 1⁄4 0.82, p 1⁄4 0.0067) and LMPR (b 1⁄4 1.87, p 1⁄4 0.015) associations were significant and that for LMIR (b 1⁄4 0.49, p 1⁄4 0.07) was marginal. No other significant associations were observed for the combined cases and controls, although marginal associations were noted for PICALM rs3851179 SNP in controls only for LMPR (b1⁄4 1.61, p1⁄4 0.046) and LMDR (b1⁄4 0.54, p1⁄4 0.09).Conclusions: Our results show that the CLU rs11136000 SNP, which is associated with reduced risk of AD, is also associated with improved memory scores in non-demented elderly subjects. Thus, in our dataset, the CLU locus had an influence on cognition that was detectable prior to clinical diagnosis of dementia. Though replication is needed, these results provide further support for CLU in AD and suggest a role for cognitive endophenotypes in genetic studies of dementia.