Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

Olivia Belbin; Minerva M Carrasquillo; Michael Crump; Oliver J Culley; Talisha A Hunter; Li Ma; Gina Bisceglio; Fanggeng Zou; Mariet Allen; Dennis W Dickson; Neill R Graff-Radford; Ronald C Petersen; Kevin Morgan; Steven G Younkin

doi:10.1007/s00439-010-0924-2

Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

Olivia Belbin, Minerva M Carrasquillo, Michael Crump, Oliver J Culley, Talisha A Hunter, Li Ma, Gina Bisceglio, Fanggeng Zou, Mariet Allen, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Kevin Morgan, Steven G Younkin

MRC Human Genetics Unit

Research output: Contribution to journal › Article › peer-review

Abstract

The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR=0.78, p=0.007), LOC651924 (OR=0.91, p=0.01) and TNK1 (OR=0.92, p=0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p

Original language	English
Pages (from-to)	273-82
Number of pages	10
Journal	Human Genetics
Volume	129
Issue number	3
DOIs	https://doi.org/10.1007/s00439-010-0924-2
Publication status	Published - Mar 2011

Keywords / Materials (for Non-textual outputs)

Adaptor Proteins, Signal Transducing
Age of Onset
Aged
Aged, 80 and over
Alzheimer Disease
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged

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10.1007/s00439-010-0924-2

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title = "Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease",

abstract = "The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA\_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR=0.78, p=0.007), LOC651924 (OR=0.91, p=0.01) and TNK1 (OR=0.92, p=0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p",

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author = "Olivia Belbin and Carrasquillo, \{Minerva M\} and Michael Crump and Culley, \{Oliver J\} and Hunter, \{Talisha A\} and Li Ma and Gina Bisceglio and Fanggeng Zou and Mariet Allen and Dickson, \{Dennis W\} and Graff-Radford, \{Neill R\} and Petersen, \{Ronald C\} and Kevin Morgan and Younkin, \{Steven G\}",

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doi = "10.1007/s00439-010-0924-2",

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T1 - Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

AU - Belbin, Olivia

AU - Carrasquillo, Minerva M

AU - Crump, Michael

AU - Culley, Oliver J

AU - Hunter, Talisha A

AU - Ma, Li

AU - Bisceglio, Gina

AU - Zou, Fanggeng

AU - Allen, Mariet

AU - Dickson, Dennis W

AU - Graff-Radford, Neill R

AU - Petersen, Ronald C

AU - Morgan, Kevin

AU - Younkin, Steven G

N1 - © Springer-Verlag 2010

PY - 2011/3

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N2 - The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR=0.78, p=0.007), LOC651924 (OR=0.91, p=0.01) and TNK1 (OR=0.92, p=0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p

AB - The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR=0.78, p=0.007), LOC651924 (OR=0.91, p=0.01) and TNK1 (OR=0.92, p=0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p

KW - Adaptor Proteins, Signal Transducing

KW - Age of Onset

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

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DO - 10.1007/s00439-010-0924-2

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SN - 0340-6717

VL - 129

SP - 273

EP - 282

JO - Human Genetics

JF - Human Genetics

IS - 3

ER -

Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

Abstract

Keywords / Materials (for Non-textual outputs)

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