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 Toglhofer, 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 Beare, Konstantinos Arfanakis, Debra A Fleischman, Meike W VernooijBernard Mazoyer, Helena Schmidt, Velandai Srikanth, David Knopman, Clifford R Jack Jr, Philippe Amouyel, Albert Hofman, Charles S DeCarli, Christophe Tzourio, Cornelia M van Duijn, David A Bennett, Reinhold Schmidt, William T Longstreth Jr, Thomas H Mosley, Myriam Fornage, Lenore J Launer, Sudha Seshadri, Mohammed Arfan Ikram, Stephanie Debette

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59 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1765 e7 - 1765 e16
Number of pages10
JournalNeurobiology of Aging
Issue number4
Publication statusPublished - 2015

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