Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease

Gary W Beecham; Badri Vardarajan; Elizabeth Blue; William Bush; James Jaworski; Sandra Barral; Anita DeStefano; Kara Hamilton-Nelson; Brian Kunkle; Eden R Martin; Adam Naj; Farid Rajabli; Christiane Reitz; Timothy Thornton; Cornelia van Duijn; Allison Goate; Sudha Seshadri; Lindsay A Farrer; Eric Boerwinkle; Gerard Schellenberg; Jonathan L Haines; Ellen Wijsman; Richard Mayeux; Margaret A Pericak-Vance

doi:10.1212/NXG.0000000000000286

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Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease

Journal article

Open access

Peer reviewed

Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease

Gary W Beecham, Badri Vardarajan, Elizabeth Blue, William Bush, James Jaworski, Sandra Barral, Anita DeStefano, Kara Hamilton-Nelson, Brian Kunkle, Eden R Martin, …

Neurology. Genetics, Vol.4(6), pp.e286-e286

2018-12

DOI: https://doi.org/10.1212/NXG.0000000000000286

PMCID: PMC6278241

PMID: 30569016

Abstract

To identify genetic variation influencing late-onset Alzheimer disease (LOAD), we used a large data set of non-Hispanic white (NHW) extended families multiply-affected by LOAD by performing whole genome sequencing (WGS). As part of the Alzheimer Disease Sequencing Project, WGS data were generated for 197 NHW participants from 42 families (affected individuals and unaffected, elderly relatives). A two-pronged approach was taken. First, variants were prioritized using heterogeneity logarithm of the odds (HLOD) and family-specific LOD scores as well as annotations based on function, frequency, and segregation with disease. Second, known Alzheimer disease (AD) candidate genes were assessed for rare variation using a family-based association test. We identified 41 rare, predicted-damaging variants that segregated with disease in the families that contributed to the HLOD or family-specific LOD regions. These included a variant in nitric oxide synthase 1 adaptor protein that segregates with disease in a family with 7 individuals with AD, as well as variants in , and . Rare-variant association identified 2 LOAD candidate genes associated with disease in these families: ( -values = 0.001) and ( -value = 0.009). These genes still showed association while controlling for common index variants, indicating the rare-variant signal is distinct from common variation that initially identified the genes as candidates. We identified multiple genes with putative damaging rare variants that segregate with disease in multiplex AD families and showed that rare variation may influence AD risk at AD candidate genes. These results identify novel AD candidate genes and show a role for rare variation in LOAD etiology, even at genes previously identified by common variation.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.57 Alzheimer's Disease
Web Of Science research areas: Clinical Neurology; Genetics & Heredity
ESI research areas: Neuroscience & Behavior

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Title: Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease
Creators: Gary W Beecham - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Badri Vardarajan - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Elizabeth Blue - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
William Bush - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
James Jaworski - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Sandra Barral - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Anita DeStefano - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Kara Hamilton-Nelson - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Brian Kunkle - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Eden R Martin - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Adam Naj - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Farid Rajabli - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Christiane Reitz - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Timothy Thornton - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Cornelia van Duijn - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Allison Goate - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Sudha Seshadri - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Lindsay A Farrer - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Eric Boerwinkle - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Gerard Schellenberg - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Jonathan L Haines - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Ellen Wijsman - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Richard Mayeux - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Margaret A Pericak-Vance - John P. Hussman Institute for Human Genomics (G.W.B., J.J., K.H.-N., B.K., E.R.M., F.R., M.A.P.-V.), University of Miami, Miller School of Medicine; Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), University of Miami, Miller School of Medicine, FL; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (B.V., S.B., C.R., R.M.), Columbia University; The Gertrude H. Segievsky Center (B.V., S.B., C.R., R.M.), Columbia University, New York Presbyterian Hospital; Division of Medical Genetics (E. Blue, E.W.), Department of Medicine, University of Washington, Seattle; Institute for Computational Biology (W.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Neurology (A.D., S.S., L.A.F.), Boston University School of Medicine; Department of Biostatistics (A.D., S.S., L.A.F.), Boston University School of Medicine, MA; School of Medicine (A.N., G.S.), University of Pennsylvania, Philadelphia; Department of Biostatistics (T.T., E.W.), University of Washington, Seattle; Erasmus Medical University (C.D.), Rotterdam, The Netherlands; Icahn School of Medicine at Mount Sinai (A.G.), New York, NY; Department of Medicine (L.A.F.), Boston University School of Medicine, MA; and University of Texas (E. Boerwinkle), Houston
Publication Details: Neurology. Genetics, Vol.4(6), pp.e286-e286
Publisher: United States
Grant note: U01 AG049507 / NIA NIH HHS U24 AG056270 / NIA NIH HHS R01 AG015819 / NIA NIH HHS R01 AG041797 / NIA NIH HHS UH3 NS100605 / NINDS NIH HHS U24 AG021886 / NIA NIH HHS R01 NS017950 / NINDS NIH HHS R01 AG017917 / NIA NIH HHS P50 AG005136 / NIA NIH HHS R01 AG033193 / NIA NIH HHS U54 HG003067 / NHGRI NIH HHS U01 AG032984 / NIA NIH HHS U54 AG052427 / NIA NIH HHS U54 HG003273 / NHGRI NIH HHS P30 AG010161 / NIA NIH HHS U01 AG052409 / NIA NIH HHS P30 AG010129 / NIA NIH HHS R01 AG054076 / NIA NIH HHS UF1 AG047133 / NIA NIH HHS
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 30569016
PMCID: PMC6278241
Record Identifier: 991031560300502976