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 - Niessen, Wiro J.
AU - More Authors, null
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). 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 - Genetic risk score
KW - GWAS
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
SN - 0197-4580
VL - 36
SP - 1765.e7-1765.e16
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 4
ER -