Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

Yuriko Katsumata; Peter T. Nelson; Sally R. Ellingson; David W. Fardo

doi:10.1016/j.neurobiolaging.2017.01.003

Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

Yuriko Katsumata, Peter T. Nelson, Sally R. Ellingson, David W. Fardo

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

22 Scopus citations

Abstract

Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer's Disease Genetics Consortium, linked to autopsy-derived neuropathological outcomes from the National Alzheimer's Coordinating Center. Of the 3251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression quantitative trait locus using 2 different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function.

Original language	English
Pages (from-to)	193.e17-193.e25
Journal	Neurobiology of Aging
Volume	53
DOIs	https://doi.org/10.1016/j.neurobiolaging.2017.01.003
State	Published - May 1 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Funding

Funders	Funder number
National Institute of Mental Health	P50MH060451, R01MH080295
National Institute of Mental Health
National Institute on Aging	P50AG005144, R01AG033193, P50AG005146, P50AG005142, R01AG035137, U01AG024904, U24AG021886, R01AG019085, R01AG025259, U01AG016976, P50AG047266, P01AG010491, R01AG013616, P50AG005133, RC2AG036528, P50AG005134, R01AG012101, P50AG005131, R01AG054060, P30AG013854, P30AG035982, P30AG028383, R01AG027944, P50AG016582, U01AG010483, K25AG043546, P50AG005136, P50AG025688, R01AG022374, P50AG005138, P50AG023501, R01AG041232, R01AG041797, R01AG021547, P50AG005681, P50AG008671, P30AG028377, R01AG041718, R37AG015473, R01AG026916, P01AG019724, R01AG030146, U01AG006781, P50AG033514, P50AG016573, P50AG016574, P30AG010133, P30AG013846, R01AG030653, P50AG016570, P50AG047366, R01AG017917, P01AG002219, P50AG005128, R01AG015819, U01AG032984, RC2AG036502, R01AG019757, R01AG020688, R01AG017173, P30AG008017, R01AG031581, P50AG047270, U24AG026395, P30AG010124, P30AG012300, P30AG010161, U24AG041689, P01AG003991, P30AG010129, P30AG019610, P30AG008051, P50AG008702
National Institute on Aging
National Human Genome Research Institute	U01HG006375, U01HG004610
National Human Genome Research Institute
National Childhood Cancer Registry – National Cancer Institute	R01CA129769
National Childhood Cancer Registry – National Cancer Institute
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS059873, P50NS039764
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
National Center for Research Resources	UL1RR029893
National Center for Research Resources
National Center for Advancing Translational Sciences (NCATS)	UL1TR000117, KL2TR001996, UL1TR001445
National Center for Advancing Translational Sciences (NCATS)

Keywords

CARTS
GWAS
KATP
PGRN
rs704180

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2017.01.003

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title = "Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2",

abstract = "Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer's Disease Genetics Consortium, linked to autopsy-derived neuropathological outcomes from the National Alzheimer's Coordinating Center. Of the 3251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression quantitative trait locus using 2 different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function.",

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author = "Yuriko Katsumata and Nelson, {Peter T.} and Ellingson, {Sally R.} and Fardo, {David W.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

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doi = "10.1016/j.neurobiolaging.2017.01.003",

language = "English",

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AU - Nelson, Peter T.

AU - Ellingson, Sally R.

AU - Fardo, David W.

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N2 - Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer's Disease Genetics Consortium, linked to autopsy-derived neuropathological outcomes from the National Alzheimer's Coordinating Center. Of the 3251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression quantitative trait locus using 2 different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function.

AB - Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer's Disease Genetics Consortium, linked to autopsy-derived neuropathological outcomes from the National Alzheimer's Coordinating Center. Of the 3251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression quantitative trait locus using 2 different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function.

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KW - PGRN

KW - rs704180

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JO - Neurobiology of Aging

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ER -

Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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