Polygenic risk of Alzheimer disease is associated with early- and late-life processes

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.