03472nas a2200781 4500008004100000022001400041245008200055210006900137260001300206300001500219490000700234520128200241653001001523653001201533653002201545653002201567653001001589653001101599653003401610653001601644653001101660653003101671653000901702653001501711653003601726653000901762653004101771100002001812700002201832700001901854700002101873700001201894700002801906700002601934700002501960700002601985700002102011700001502032700001602047700002102063700002002084700002102104700001902125700002202144700002802166700002202194700002302216700002102239700002002260700002302280700002202303700002202325700002202347700001902369700002102388700002402409700002302433700002202456700002202478700002702500700002202527700002002549700002202569700002002591700002002611700002302631856003602654 2015 eng d a1558-149700aAssociation of Alzheimer's disease GWAS loci with MRI markers of brain aging.0 aAssociation of Alzheimers disease GWAS loci with MRI markers of c2015 Apr a1765.e7-160 v363 a
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.
10aAging10aAlleles10aAlzheimer Disease10aApolipoproteins E10aBrain10aFemale10aGenome-Wide Association Study10aHippocampus10aHumans10aMagnetic Resonance Imaging10aMale10aOrgan Size10aPolymorphism, Single Nucleotide10aRisk10aSialic Acid Binding Ig-like Lectin 31 aChauhan, Ganesh1 aAdams, Hieab, H H1 aBis, Joshua, C1 aWeinstein, Galit1 aYu, Lei1 aTöglhofer, Anna, Maria1 aSmith, Albert, Vernon1 avan der Lee, Sven, J1 aGottesman, Rebecca, F1 aThomson, Russell1 aWang, Jing1 aYang, Qiong1 aNiessen, Wiro, J1 aLopez, Oscar, L1 aBecker, James, T1 aPhan, Thanh, G1 aBeare, Richard, J1 aArfanakis, Konstantinos1 aFleischman, Debra1 aVernooij, Meike, W1 aMazoyer, Bernard1 aSchmidt, Helena1 aSrikanth, Velandai1 aKnopman, David, S1 aJack, Clifford, R1 aAmouyel, Philippe1 aHofman, Albert1 aDeCarli, Charles1 aTzourio, Christophe1 aDuijn, Cornelia, M1 aBennett, David, A1 aSchmidt, Reinhold1 aLongstreth, William, T1 aMosley, Thomas, H1 aFornage, Myriam1 aLauner, Lenore, J1 aSeshadri, Sudha1 aIkram, Arfan, M1 aDebette, Stephanie uhttps://chs-nhlbi.org/node/6815