Association of common KIBRA variants with episodic memory and AD risk
Abstract KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome-wide association study (GWAS) of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's...
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| Veröffentlicht in: | Neurobiology of aging 2011-03, Vol.32 (3), p.557.e1-557.e9 |
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| creator | Burgess, Jeremy D Pedraza, Otto Graff-Radford, Neill R Hirpa, Meron Zou, Fanggeng Miles, Richard Nguyen, Thuy Li, Ma Lucas, John A Ivnik, Robert J Crook, Julia Pankratz, V. Shane Dickson, Dennis W Petersen, Ronald C Younkin, Steven G Ertekin-Taner, Nilüfer |
| description | Abstract KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome-wide association study (GWAS) of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's disease (AD) risk in 1 study, which also found overexpression of KIBRA in memory-related brain regions of AD. We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's disease (LOAD) patients vs. 2842 controls, including African-Americans. We found significantly reduced risk for rs17070145 T allele in the older African-American subjects ( p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect ( p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex ( p = 0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations. |
| doi_str_mv | 10.1016/j.neurobiolaging.2010.11.004 |
| format | Article |
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We found significantly reduced risk for rs17070145 T allele in the older African-American subjects ( p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect ( p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex ( p = 0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/j.neurobiolaging.2010.11.004</identifier><identifier>PMID: 21185624</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - complications ; Alzheimer Disease - epidemiology ; Alzheimer Disease - genetics ; Alzheimer's disease ; Association studies in genetics ; Case control studies ; Episodic memory ; Female ; Gene expression ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study - methods ; Genotype ; Humans ; Internal Medicine ; Intracellular Signaling Peptides and Proteins ; KIBRA ; Male ; Mental Recall - physiology ; Meta-Analysis as Topic ; Middle Aged ; Neurology ; Neuropsychological Tests ; Phosphoproteins ; Polymorphism, Single Nucleotide - genetics ; Proteins - genetics ; Risk Factors ; United States - epidemiology</subject><ispartof>Neurobiology of aging, 2011-03, Vol.32 (3), p.557.e1-557.e9</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. 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All rights reserved. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-36ba269da3f3ed122351845b928b75bf8f72484082cfeb237f370bdafb9dee833</citedby><cites>FETCH-LOGICAL-c549t-36ba269da3f3ed122351845b928b75bf8f72484082cfeb237f370bdafb9dee833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neurobiolaging.2010.11.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21185624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burgess, Jeremy D</creatorcontrib><creatorcontrib>Pedraza, Otto</creatorcontrib><creatorcontrib>Graff-Radford, Neill R</creatorcontrib><creatorcontrib>Hirpa, Meron</creatorcontrib><creatorcontrib>Zou, Fanggeng</creatorcontrib><creatorcontrib>Miles, Richard</creatorcontrib><creatorcontrib>Nguyen, Thuy</creatorcontrib><creatorcontrib>Li, Ma</creatorcontrib><creatorcontrib>Lucas, John A</creatorcontrib><creatorcontrib>Ivnik, Robert J</creatorcontrib><creatorcontrib>Crook, Julia</creatorcontrib><creatorcontrib>Pankratz, V. 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We found significantly reduced risk for rs17070145 T allele in the older African-American subjects ( p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect ( p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex ( p = 0.06) but not cerebellum. 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We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's disease (LOAD) patients vs. 2842 controls, including African-Americans. We found significantly reduced risk for rs17070145 T allele in the older African-American subjects ( p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect ( p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex ( p = 0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21185624</pmid><doi>10.1016/j.neurobiolaging.2010.11.004</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Neurobiology of aging, 2011-03, Vol.32 (3), p.557.e1-557.e9 |
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| subjects | Aged Aged, 80 and over Alzheimer Disease - complications Alzheimer Disease - epidemiology Alzheimer Disease - genetics Alzheimer's disease Association studies in genetics Case control studies Episodic memory Female Gene expression Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study - methods Genotype Humans Internal Medicine Intracellular Signaling Peptides and Proteins KIBRA Male Mental Recall - physiology Meta-Analysis as Topic Middle Aged Neurology Neuropsychological Tests Phosphoproteins Polymorphism, Single Nucleotide - genetics Proteins - genetics Risk Factors United States - epidemiology |
| title | Association of common KIBRA variants with episodic memory and AD risk |
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