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Alzheimers Dement. 2017 Jul;13(7):727-738. doi: 10.1016/j.jalz.2016.12.012. Epub 2017 Feb 7.

Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

Collaborators (155)

Adams PM, Albert MS, Albin RL, Apostolova LG, Arnold SE, Asthana S, Atwood CS, Barmada MM, Barnes LL, Beach TG, Becker JT, Bigio EH, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Burke JR, Cairns NJ, Cao C, Carlson CS, Carlsson CM, Carney RM, Carrasquillo MM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Cribbs DH, Crocco EA, Cruchaga C, De Jager PL, DeCarli C, DeKosky ST, Demirci FY, Dick M, Dickson DW, Doody RS, Duara R, Ertekin-Taner N, Faber KM, Fairchild TJ, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Glass JD, Graff-Radford NR, Green RC, Growdon JH, Hakonarson H, Hamilton RL, Hardy J, Harrell LE, Head E, Honig LS, Huebinger RM, Huentelman MJ, Hulette CM, Hyman BT, Jarvik GP, Jicha GA, Jin LW, Karydas A, Kauwe JSK, Kaye JA, Kim R, Koo EH, Kowall NW, Kramer JH, LaFerla FM, Lah JJ, Leverenz JB, Levey AI, Li G, Lieberman AP, Lin CF, Lopez OL, Lyketsos CG, Mack WJ, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Morris JC, Mukherjee S, Murrell JR, Myers AJ, O'Bryant S, Olichney JM, Pankratz VS, Parisi JE, Partch A, Paulson HL, Perry W, Peskind E, Petersen RC, Pierce A, Poon WW, Potter H, Quinn JF, Raj A, Raskind M, Reisberg B, Reisch JS, Reitz C, Ringman JM, Roberson ED, Rogaeva E, Rosen HJ, Rosenberg RN, Royall DR, Sager MA, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Tanzi RE, Thornton-Wells TA, Trojanowski JQ, Troncoso JC, Tsuang DW, Van Deerlin VM, Van Eldik LJ, Vardarajan BN, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Wishnek S, Woltjer RL, Wright CB, Wu CK, Yu CE, Yu L, Zhang X.

Author information

1
Neurogenetics and Integrated Genomics, Andover Innovative Medicines Institute, Eisai Inc, Andover, MA, USA; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
2
Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
3
Department of Neurology, Boston University Schools of Medicine, Boston, MA, USA.
4
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
5
The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
6
Department of Neurological Sciences and Rush Alzheimer's Disease Center, Chicago, IL, USA.
7
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
8
Department of Biology, North Carolina A&T State University, Greensboro, NC, USA.
9
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
10
Department of Medicine, University of Washington, Seattle, WA, USA.
11
Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
12
Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology & Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
13
Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
14
Department of Mental Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
15
Department of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, USA.
16
Department of Neurology, University of Louisville, Louisville, KY, USA.
17
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.
18
Department of Psychiatry, Indiana University, Indianapolis, IN, USA; Regenstrief Institute, Inc, Indianapolis, IN, USA.
19
Regenstrief Institute, Inc, Indianapolis, IN, USA; Department of Medicine, Indiana University, Indianapolis, IN, USA.
20
Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
21
University of Pittsburgh Alzheimer's Disease Research Center and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
22
Department of Biology, Brigham Young University, Provo, UT, USA.
23
Department of Epidemiology, University of Washington, Seattle, WA, USA; National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
24
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
25
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Group Health, Group Health Research Institute, Seattle, WA, USA.
26
Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA; Department of Neurological Sciences and Rush Alzheimer's Disease Center, Chicago, IL, USA; National Center for PTSD, Behavioral Science Division, Boston VA Healthcare System, Boston, MA, USA.
27
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
28
Department of Pathology, Stanford University, Stanford, CA, USA.
29
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
30
Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Department of Psychiatry, University of Arizona, Phoenix, AZ, USA; Banner Alzheimer's Institute, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
31
The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
32
Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada; Cambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
33
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
34
Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
35
PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA.
36
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
37
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
38
Department of Biostatistics, Boston University Schools of Public Health, Boston, MA, USA.
39
Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA; Department of Neurology, Boston University Schools of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University Schools of Public Health, Boston, MA, USA; Department of Ophthalmology, Boston University Schools of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University Schools of Public Health, Boston, MA, USA. Electronic address: farrer@bu.edu.

Abstract

INTRODUCTION:

Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.

METHODS:

We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset.

RESULTS:

Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6).

DISCUSSION:

Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

KEYWORDS:

APOE interaction; Alzheimer's disease; Genome-wide association; Transethnic

PMID:
28183528
PMCID:
PMC5496797
DOI:
10.1016/j.jalz.2016.12.012
[Indexed for MEDLINE]
Free PMC Article

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