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Genetic architecture of resilience of executive functioning.

The genetic basis of resilience, defined as better cognitive functioning than predicted based on neuroimaging or neuropathology, is not well understood. Our objective was to identify genetic variation associated with executive functioning resilience. We computed residuals from regression models of e... Full description

Journal Title: Brain imaging and behavior December 2012, Vol.6(4), pp.621-633
Main Author: Mukherjee, Shubhabrata
Other Authors: Kim, Sungeun , Gibbons, Laura E , Nho, Kwangsik , Risacher, Shannon L , Glymour, M Maria , Habeck, Christian , Lee, Grace J , Mormino, Elizabeth , Ertekin-Taner, Nilüfer , Montine, Thomas J , Decarli, Charles , Saykin, Andrew J , Crane, Paul K , Mukherjee, Shubhabrata
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9184-1
Link: http://search.proquest.com/docview/1285464756/?pq-origsite=primo
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title: Genetic architecture of resilience of executive functioning.
format: Article
creator:
  • Mukherjee, Shubhabrata
  • Kim, Sungeun
  • Gibbons, Laura E
  • Nho, Kwangsik
  • Risacher, Shannon L
  • Glymour, M Maria
  • Habeck, Christian
  • Lee, Grace J
  • Mormino, Elizabeth
  • Ertekin-Taner, Nilüfer
  • Montine, Thomas J
  • Decarli, Charles
  • Saykin, Andrew J
  • Crane, Paul K
  • Mukherjee, Shubhabrata
subjects:
  • Aged–Epidemiology
  • Aged, 80 and Over–Genetics
  • Alzheimer Disease–Epidemiology
  • Europe–Epidemiology
  • Executive Function–Genetics
  • Female–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Humans–Genetics
  • Incidence–Genetics
  • Male–Genetics
  • Middle Aged–Genetics
  • Polymorphism, Single Nucleotide–Genetics
  • Resilience, Psychological–Genetics
  • Risk Factors–Genetics
ispartof: Brain imaging and behavior, December 2012, Vol.6(4), pp.621-633
description: The genetic basis of resilience, defined as better cognitive functioning than predicted based on neuroimaging or neuropathology, is not well understood. Our objective was to identify genetic variation associated with executive functioning resilience. We computed residuals from regression models of executive functioning, adjusting for age, sex, education, Hachinski score, and MRI findings (lacunes, cortical thickness, volumes of white matter hyperintensities and hippocampus). We estimated heritability and analyzed these residuals in models for each SNP. We further evaluated our most promising SNP result by evaluating cis-associations with brain levels of nearby ( plus or minus 100 kb) genes from a companion data set, and comparing expression levels in cortex and cerebellum from decedents with AD with those from other non-AD diseases. Complete data were available for 750 ADNI participants of European descent. Executive functioning resilience was highly heritable (H super(2)=0.76; S.E. = 0.44). rs3748348 on chromosome 14 in the region of RNASE13 was associated with executive functioning resilience (p-value=4.3110 super(-7)). rs3748348 is in strong linkage disequilibrium (D' of 1.00 and 0.96) with SNPs that map to TPPP2, a member of the alpha -synuclein family of proteins. We identified nominally significant associations between rs3748348 and expression levels of three genes (FLJ10357, RNASE2, and NDRG2). The strongest association was for FLJ10357 in cortex, which also had the most significant difference in expression between AD and non-AD brains, with greater expression in cortex of decedents with AD (p-value=710 super(-7)). Further research is warranted to determine whether this signal can be replicated and whether other loci may be associated with cognitive resilience.
language: eng
source:
identifier: E-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9184-1
fulltext: fulltext
issn:
  • 19317565
  • 1931-7565
url: Link


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titleGenetic architecture of resilience of executive functioning.
creatorMukherjee, Shubhabrata ; Kim, Sungeun ; Gibbons, Laura E ; Nho, Kwangsik ; Risacher, Shannon L ; Glymour, M Maria ; Habeck, Christian ; Lee, Grace J ; Mormino, Elizabeth ; Ertekin-Taner, Nilüfer ; Montine, Thomas J ; Decarli, Charles ; Saykin, Andrew J ; Crane, Paul K ; Mukherjee, Shubhabrata
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ispartofBrain imaging and behavior, December 2012, Vol.6(4), pp.621-633
identifierE-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9184-1
subjectAged–Epidemiology ; Aged, 80 and Over–Genetics ; Alzheimer Disease–Epidemiology ; Europe–Epidemiology ; Executive Function–Genetics ; Female–Genetics ; Genetic Predisposition to Disease–Genetics ; Humans–Genetics ; Incidence–Genetics ; Male–Genetics ; Middle Aged–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Resilience, Psychological–Genetics ; Risk Factors–Genetics
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descriptionThe genetic basis of resilience, defined as better cognitive functioning than predicted based on neuroimaging or neuropathology, is not well understood. Our objective was to identify genetic variation associated with executive functioning resilience. We computed residuals from regression models of executive functioning, adjusting for age, sex, education, Hachinski score, and MRI findings (lacunes, cortical thickness, volumes of white matter hyperintensities and hippocampus). We estimated heritability and analyzed these residuals in models for each SNP. We further evaluated our most promising SNP result by evaluating cis-associations with brain levels of nearby ( plus or minus 100 kb) genes from a companion data set, and comparing expression levels in cortex and cerebellum from decedents with AD with those from other non-AD diseases. Complete data were available for 750 ADNI participants of European descent. Executive functioning resilience was highly heritable (H super(2)=0.76; S.E. = 0.44). rs3748348 on chromosome 14 in the region of RNASE13 was associated with executive functioning resilience (p-value=4.3110 super(-7)). rs3748348 is in strong linkage disequilibrium (D' of 1.00 and 0.96) with SNPs that map to TPPP2, a member of the alpha -synuclein family of proteins. We identified nominally significant associations between rs3748348 and expression levels of three genes (FLJ10357, RNASE2, and NDRG2). The strongest association was for FLJ10357 in cortex, which also had the most significant difference in expression between AD and non-AD brains, with greater expression in cortex of decedents with AD (p-value=710 super(-7)). Further research is warranted to determine whether this signal can be replicated and whether other loci may be associated with cognitive resilience.
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2Gibbons, Laura E
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7Lee, Grace J
8Mormino, Elizabeth
9Ertekin-Taner, Nilüfer
10Montine, Thomas J
11Decarli, Charles
12Saykin, Andrew J
13Crane, Paul K
titleGenetic architecture of resilience of executive functioning.
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0Aged–Epidemiology
1Aged, 80 and Over–Genetics
2Alzheimer Disease–Epidemiology
3Europe–Epidemiology
4Executive Function–Genetics
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9Saykin, Andrew J
10Morris, John
11Liu, Enchi
12Montine, Tom
13Gamst, Anthony
14Thomas, Ronald G
15Donohue, Michael
16Walter, Sarah
17Gessert, Devon
18Sather, Tamie
19Harvey, Danielle
20Kornak, John
21Dale, Anders
22Bernstein, Matthew
23Felmlee, Joel
24Fox, Nick
25Thompson, Paul
26Schuff, Norbert
27Alexander, Gene
28Decarli, Charles
29Bandy, Dan
30Koeppe, Robert A
31Foster, Norm
32Reiman, Eric M
33Chen, Kewei
34Mathis, Chet
35Cairns, Nigel J
36Taylor-Reinwald, Lisa
37Trojanowki, J Q
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39Lee, Virginia M Y
40Korecka, Magdalena
41Crawford, Karen
42Neu, Scott
43Foroud, Tatiana M
44Potkin, Steven
45Shen, Li
46Kachaturian, Zaven
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52Lind, Betty
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54Schneider, Lon S
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56Spann, Bryan M
57Brewer, James
58Vanderswag, Helen
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60Lord, Joanne L
61Johnson, Kris
62Doody, Rachelle S
63Villanueva-Meyer, Javier
64Chowdhury, Munir
65Stern, Yaakov
66Honig, Lawrence S
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citationpf 621 pt 633 vol 6 issue 4
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titleGenetic architecture of resilience of executive functioning.
authorMukherjee, Shubhabrata ; Kim, Sungeun ; Gibbons, Laura E ; Nho, Kwangsik ; Risacher, Shannon L ; Glymour, M Maria ; Habeck, Christian ; Lee, Grace J ; Mormino, Elizabeth ; Ertekin-Taner, Nilüfer ; Montine, Thomas J ; Decarli, Charles ; Saykin, Andrew J ; Crane, Paul K ; Mukherjee, Shubhabrata
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1Aged, 80 and Over–Genetics
2Alzheimer Disease–Epidemiology
3Europe–Epidemiology
4Executive Function–Genetics
5Female–Genetics
6Genetic Predisposition to Disease–Genetics
7Humans–Genetics
8Incidence–Genetics
9Male–Genetics
10Middle Aged–Genetics
11Polymorphism, Single Nucleotide–Genetics...
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7Lee, Grace J
8Mormino, Elizabeth
9Ertekin-Taner, Nilüfer
10Montine, Thomas J
11Decarli, Charles
12Saykin, Andrew J
13Crane, Paul K
14Weiner, Michael
15Aisen, Paul
16Petersen, Ronald
17Jack, Clifford R
18Jagust, William
19Trojanowki, John Q
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21Beckett, Laurel
22Green, Robert C
23Morris, John
24Liu, Enchi
25Montine, Tom
26Gamst, Anthony
27Thomas, Ronald G
28Donohue, Michael
29Walter, Sarah
30Gessert, Devon
31Sather, Tamie
32Harvey, Danielle
33Kornak, John
34Dale, Anders
35Bernstein, Matthew
36Felmlee, Joel
37Fox, Nick
38Thompson, Paul
39Schuff, Norbert
40Alexander, Gene
41Bandy, Dan
42Koeppe, Robert A
43Foster, Norm
44Reiman, Eric M
45Chen, Kewei
46Mathis, Chet
47Cairns, Nigel J
48Taylor-Reinwald, Lisa
49Trojanowki, J Q
50Shaw, Les
51Lee, Virginia M Y
52Korecka, Magdalena
53Crawford, Karen
54Neu, Scott
55Foroud, Tatiana M
56Potkin, Steven
57Shen, Li
58Kachaturian, Zaven
59Frank, Richard
60Snyder, Peter J
61Molchan, Susan
62Kaye, Jeffrey
63Quinn, Joseph
64Lind, Betty
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69Brewer, James
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19Harvey, Danielle
20Kornak, John
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22Bernstein, Matthew
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49Molchan, Susan
50Kaye, Jeffrey
51Quinn, Joseph
52Lind, Betty
53Dolen, Sara
54Schneider, Lon S
55Pawluczyk, Sonia
56Spann, Bryan M
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66Honig, Lawrence S
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71Leon, Sue
72Mintun, Mark A
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81Shah, Raj C
82Duara, Ranjan
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84Roberts, Peggy
85Albert, Marilyn
86Onyike, Chiadi
87Kielb, Stephanie
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89de Leon, Mony J
90Glodzik, Lidia
91De Santi, Susan
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93Petrella, Jeffrey R
94Coleman, R Edward
95Arnold, Steven E
96Karlawish, Jason H
97Wolk, David
98Smith, Charles D
99Jicha, Greg
100...
atitleGenetic architecture of resilience of executive functioning.
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