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 - Toglhofer, 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
AU - Arfanakis, Konstantinos
AU - Fleischman, Debra A
AU - Vernooij, Meike W
AU - Mazoyer, Bernard
AU - Schmidt, Helena
AU - Srikanth, Velandai
AU - Knopman, David
AU - Jack Jr, Clifford R
AU - Amouyel, Philippe
AU - Hofman, Albert
AU - DeCarli, Charles S
AU - Tzourio, Christophe
AU - van Duijn, Cornelia M
AU - Bennett, David A
AU - Schmidt, Reinhold
AU - Longstreth Jr, William T
AU - Mosley, Thomas H
AU - Fornage, Myriam
AU - Launer, Lenore J
AU - Seshadri, Sudha
AU - Ikram, Mohammed Arfan
AU - Debette, Stephanie
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.
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.
UR - http://www.sciencedirect.com/science/article/pii/S0197458014008458
U2 - 10.1016/j.neurobiolaging.2014.12.028
DO - 10.1016/j.neurobiolaging.2014.12.028
M3 - Article
C2 - 25670335
VL - 36
SP - 1765 e7 - 1765 e16
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 4
ER -