Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

Ganesh Chauhan; Hieab H.H. Adams; Joshua C. Bis; Galit Weinstein; Lei Yu; Anna Maria Töglhofer; Albert Vernon Smith; Sven J. van der Lee; Rebecca F. Gottesman; Russell Thomson; Jing Wang; Qiong Yang; Wiro J. Niessen; Oscar L. Lopez; James T. Becker; Thanh G. Phan; Richard J. Beare; Konstantinos Arfanakis; Debra Fleischman; Meike W. Vernooij; Bernard Mazoyer; Helena Schmidt; Velandai Srikanth; David S. Knopman; Clifford R. Jack; Philippe Amouyel; Albert Hofman; Charles DeCarli; Christophe Tzourio; Cornelia M. van Duijn; David A. Bennett; Reinhold Schmidt; William T. Longstreth; Thomas H. Mosley; Myriam Fornage; Lenore J. Launer; Sudha Seshadri; M. Arfan Ikram; Stephanie Debette

doi:10.1016/j.neurobiolaging.2014.12.028

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

Ganesh Chauhan, Hieab H.H. Adams, Joshua C. Bis, Galit Weinstein, Lei Yu, Anna Maria Töglhofer, Albert Vernon Smith, Sven J. van der Lee, Rebecca F. Gottesman, Russell Thomson, Jing Wang, Qiong Yang, Wiro J. Niessen, Oscar L. Lopez, James T. Becker, Thanh G. Phan, Richard J. Beare, Konstantinos Arfanakis, Debra Fleischman, Meike W. VernooijBernard Mazoyer, Helena Schmidt, Velandai Srikanth, David S. Knopman, Clifford R. Jack, Philippe Amouyel, Albert Hofman, Charles DeCarli, Christophe Tzourio, Cornelia M. van Duijn, David A. Bennett, Reinhold Schmidt, William T. Longstreth, Thomas H. Mosley, Myriam Fornage, Lenore J. Launer, Sudha Seshadri, M. Arfan Ikram, Stephanie Debette

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Abstract

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

Original language	English
Pages (from-to)	1765.e7-1765.e16
Journal	Neurobiology of Aging
Volume	36
Issue number	4
DOIs	https://doi.org/10.1016/j.neurobiolaging.2014.12.028
State	Published - 1 Apr 2015
Externally published	Yes

Keywords

Alzheimer
GWAS
Genetic risk score
Hippocampal volume
MRI-Markers

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10.1016/j.neurobiolaging.2014.12.028

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Chauhan, G., Adams, H. H. H., Bis, J. C., Weinstein, G., Yu, L., Töglhofer, A. M., Smith, A. V., van der Lee, S. J., Gottesman, R. F., Thomson, R., Wang, J., Yang, Q., Niessen, W. J., Lopez, O. L., Becker, J. T., Phan, T. G., Beare, R. J., Arfanakis, K., Fleischman, D., ... Debette, S. (2015). Association of Alzheimer's disease GWAS loci with MRI markers of brain aging. Neurobiology of Aging, 36(4), 1765.e7-1765.e16. https://doi.org/10.1016/j.neurobiolaging.2014.12.028

@article{a17174953b8e4f5199bbc8d441902d4b,

title = "Association of Alzheimer's disease GWAS loci with MRI markers of brain aging",

abstract = "Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.",

keywords = "Alzheimer, GWAS, Genetic risk score, Hippocampal volume, MRI-Markers",

author = "Ganesh Chauhan and Adams, {Hieab H.H.} and Bis, {Joshua C.} and Galit Weinstein and Lei Yu and T{\"o}glhofer, {Anna Maria} and Smith, {Albert Vernon} and {van der Lee}, {Sven J.} and Gottesman, {Rebecca F.} and Russell Thomson and Jing Wang and Qiong Yang and Niessen, {Wiro J.} and Lopez, {Oscar L.} and Becker, {James T.} and Phan, {Thanh G.} and Beare, {Richard J.} and Konstantinos Arfanakis and Debra Fleischman and Vernooij, {Meike W.} and Bernard Mazoyer and Helena Schmidt and Velandai Srikanth and Knopman, {David S.} and Jack, {Clifford R.} and Philippe Amouyel and Albert Hofman and Charles DeCarli and Christophe Tzourio and {van Duijn}, {Cornelia M.} and Bennett, {David A.} and Reinhold Schmidt and Longstreth, {William T.} and Mosley, {Thomas H.} and Myriam Fornage and Launer, {Lenore J.} and Sudha Seshadri and Ikram, {M. Arfan} and Stephanie Debette",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = apr,

day = "1",

doi = "10.1016/j.neurobiolaging.2014.12.028",

language = "English",

volume = "36",

pages = "1765.e7--1765.e16",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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Chauhan, G, Adams, HHH, Bis, JC, Weinstein, G, Yu, L, Töglhofer, AM, Smith, AV, van der Lee, SJ, Gottesman, RF, Thomson, R, Wang, J, Yang, Q, Niessen, WJ, Lopez, OL, Becker, JT, Phan, TG, Beare, RJ, Arfanakis, K, Fleischman, D, Vernooij, MW, Mazoyer, B, Schmidt, H, Srikanth, V, Knopman, DS, Jack, CR, Amouyel, P, Hofman, A, DeCarli, C, Tzourio, C, van Duijn, CM, Bennett, DA, Schmidt, R, Longstreth, WT, Mosley, TH, Fornage, M, Launer, LJ, Seshadri, S, Ikram, MA & Debette, S 2015, 'Association of Alzheimer's disease GWAS loci with MRI markers of brain aging', Neurobiology of Aging, vol. 36, no. 4, pp. 1765.e7-1765.e16. https://doi.org/10.1016/j.neurobiolaging.2014.12.028

TY - JOUR

T1 - Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

AU - Chauhan, Ganesh

AU - Adams, Hieab H.H.

AU - Bis, Joshua C.

AU - Weinstein, Galit

AU - Yu, Lei

AU - Töglhofer, Anna Maria

AU - Smith, Albert Vernon

AU - van der Lee, Sven J.

AU - Gottesman, Rebecca F.

AU - Thomson, Russell

AU - Wang, Jing

AU - Yang, Qiong

AU - Niessen, Wiro J.

AU - Lopez, Oscar L.

AU - Becker, James T.

AU - Phan, Thanh G.

AU - Beare, Richard J.

AU - Arfanakis, Konstantinos

AU - Fleischman, Debra

AU - Vernooij, Meike W.

AU - Mazoyer, Bernard

AU - Schmidt, Helena

AU - Srikanth, Velandai

AU - Knopman, David S.

AU - Jack, Clifford R.

AU - Amouyel, Philippe

AU - Hofman, Albert

AU - DeCarli, Charles

AU - Tzourio, Christophe

AU - van Duijn, Cornelia M.

AU - Bennett, David A.

AU - Schmidt, Reinhold

AU - Longstreth, William T.

AU - Mosley, Thomas H.

AU - Fornage, Myriam

AU - Launer, Lenore J.

AU - Seshadri, Sudha

AU - Ikram, M. Arfan

AU - Debette, Stephanie

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

AB - Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

KW - Alzheimer

KW - GWAS

KW - Genetic risk score

KW - Hippocampal volume

KW - MRI-Markers

UR - http://www.scopus.com/inward/record.url?scp=84925295495&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2014.12.028

DO - 10.1016/j.neurobiolaging.2014.12.028

M3 - Article

C2 - 25670335

AN - SCOPUS:84925295495

SN - 0197-4580

VL - 36

SP - 1765.e7-1765.e16

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 4

ER -

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

Abstract

Keywords

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