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

G Chauhan; Hieab Adams; JC Bis; G Weinstein; L Yu; AM Toglhofer; AV Smith; Sven van der Lee; RF Gottesmanm; R Thomson; Johnny Wang; Q Yang; Wiro Niessen; OL Lopez; JT Becker; TG Phan; RJ Beare; K Arfanakis; D Fleischman; Meike Vernooij; B Mazoyer; Heléna Schmidt; V Srikanth; DS Knopman; CR Jack; P Amouyel; Bert Hofman; C DeCarli; C Tzourio; Cornelia Duijn; DA Bennett; R Schmidt; WT Longstreth; TH Mosley; M Fornage; LJ Launer; S Seshadri; Arfan Ikram; S Debette

doi:10.1016/j.neurobiolaging.2014.12.028

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

G Chauhan, Hieab Adams, JC Bis, G Weinstein, L Yu, AM Toglhofer, AV Smith, Sven van der Lee, RF Gottesmanm, R Thomson, Johnny Wang, Q Yang, Wiro Niessen, OL Lopez, JT Becker, TG Phan, RJ Beare, K Arfanakis, D Fleischman, Meike VernooijB Mazoyer, Heléna Schmidt, V Srikanth, DS Knopman, CR Jack, P Amouyel, Bert Hofman, C DeCarli, C Tzourio, Cornelia Duijn, DA Bennett, R Schmidt, WT Longstreth, TH Mosley, M Fornage, LJ Launer, S Seshadri, Arfan Ikram, S 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). A weighted 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. (C) 2015 Elsevier Inc. All rights reserved.

Original language	Undefined/Unknown
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
Publication status	Published - 2015

Research programs

EMC COEUR-09
EMC NIHES-01-64-01
EMC NIHES-03-30-02
EMC NIHES-03-30-03

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10.1016/j.neurobiolaging.2014.12.028

Cite this

Chauhan, G., Adams, H., Bis, JC., Weinstein, G., Yu, L., Toglhofer, AM., Smith, AV., van der Lee, S., Gottesmanm, RF., Thomson, R., Wang, J., Yang, Q., Niessen, W., Lopez, OL., Becker, JT., Phan, TG., Beare, RJ., 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

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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). A weighted 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. (C) 2015 Elsevier Inc. All rights reserved.",

author = "G Chauhan and Hieab Adams and JC Bis and G Weinstein and L Yu and AM Toglhofer and AV Smith and {van der Lee}, Sven and RF Gottesmanm and R Thomson and Johnny Wang and Q Yang and Wiro Niessen and OL Lopez and JT Becker and TG Phan and RJ Beare and K Arfanakis and D Fleischman and Meike Vernooij and B Mazoyer and Hel{\'e}na Schmidt and V Srikanth and DS Knopman and CR Jack and P Amouyel and Bert Hofman and C DeCarli and C Tzourio and Cornelia Duijn and DA Bennett and R Schmidt and WT Longstreth and TH Mosley and M Fornage and LJ Launer and S Seshadri and Arfan Ikram and S Debette",

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Chauhan, G, Adams, H, Bis, JC, Weinstein, G, Yu, L, Toglhofer, AM, Smith, AV, van der Lee, S, Gottesmanm, RF, Thomson, R, Wang, J, Yang, Q, Niessen, W, Lopez, OL, Becker, JT, Phan, TG, Beare, RJ, Arfanakis, K, Fleischman, D, Vernooij, M, Mazoyer, B, Schmidt, H, Srikanth, V, Knopman, DS, Jack, CR, Amouyel, P, Hofman, B, DeCarli, C, Tzourio, C, Duijn, C, Bennett, DA, Schmidt, R, Longstreth, WT, Mosley, TH, Fornage, M, Launer, LJ, Seshadri, S, Ikram, A & 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, G

AU - Adams, Hieab

AU - Bis, JC

AU - Weinstein, G

AU - Yu, L

AU - Toglhofer, AM

AU - Smith, AV

AU - van der Lee, Sven

AU - Gottesmanm, RF

AU - Thomson, R

AU - Wang, Johnny

AU - Yang, Q

AU - Niessen, Wiro

AU - Lopez, OL

AU - Becker, JT

AU - Phan, TG

AU - Beare, RJ

AU - Arfanakis, K

AU - Fleischman, D

AU - Vernooij, Meike

AU - Mazoyer, B

AU - Schmidt, Heléna

AU - Srikanth, V

AU - Knopman, DS

AU - Jack, CR

AU - Amouyel, P

AU - Hofman, Bert

AU - DeCarli, C

AU - Tzourio, C

AU - Duijn, Cornelia

AU - Bennett, DA

AU - Schmidt, R

AU - Longstreth, WT

AU - Mosley, TH

AU - Fornage, M

AU - Launer, LJ

AU - Seshadri, S

AU - Ikram, Arfan

AU - Debette, S

PY - 2015

Y1 - 2015

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). A weighted 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. (C) 2015 Elsevier Inc. All rights reserved.

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). A weighted 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. (C) 2015 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.neurobiolaging.2014.12.028

DO - 10.1016/j.neurobiolaging.2014.12.028

M3 - Article

C2 - 25670335

SN - 0197-4580

VL - 36

SP - 1765.e7-1765.e16

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 4

ER -