We studied the effects of SNPs at different LOAD risk genes 6– 8: the complement component (3b/4b) receptor 1 ( CR1), phosphatidylinositol-binding clathrin assembly protein ( PICALM), clusterin ( CLU), bridging integrator 1 ( BIN1), and APOE. We used a multilocus analysis approach to evaluate the association between LOAD genetic variants and episodic memory. 3 Because of the large number of single nucleotide polymorphisms (SNPs) implicated in GWAS, many of the multilocus methods previously proposed are not suitable, and two-step approaches 4, 5 are more appropriate. Most analytic approaches use single marker association analysis however, empirical evidence from model organisms 1 and human studies 2 suggests that interactions among loci broadly contribute to complex traits.
However, the reported effect sizes are small, suggesting that additional genes contributing to the overall risk remain to be identified. Recent genome-wide association (GWAS) studies have associated susceptibility variants with late-onset Alzheimer disease (LOAD). Louis, MO Departments of Neurology (M.R.F.) and Medical and Molecular Genetics (T.F.), Indiana University School of Medicine, Indianapolis Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences (R.D.-A.), Bethesda, MD Rush Alzheimer's Disease Center (D.A.B., R.S.W.), Rush University Medical Center, Chicago, IL Department of Neurology (N.G.-R.), Mayo Clinic College of Medicine, Jacksonville, FL Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN Department of Psychiatry (R.A.S.), University of Pittsburgh, Pittsburgh, PA and Key Laboratory of Mental Health (J.O.), Institute of Psychology, Chinese Academy of Sciences, Beijing, China. Sergievsky Center, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Department of Neurology (S.B., Y.S., R.M.), Columbia University College of Physicians and Surgeons, New York, NY Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, and Department of Neurology (T.B.), University of Washington, Seattle Department of Psychiatry (A.G.), Washington University School of Medicine, St.
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