Nelson PT et al, “Reassessment of risk alleles in HS-Aging”
Supplemental Material
Inclusion and exclusion criteria
An HS case must have at least one of thefollowing NP fields: NPPHIPP = 1, NPCHIPP = 1, NPSCL=1, NPTHPRIM=11, or NPTHSECN=11.
Terminologic definitions from NACC:
NPPHIPP:” (1 yes, 2 no)
NPCHIPP:
Hippocampal sclerosis-Contributing; “Is there a contributing pathology diagnosis of hippocampal sclerosis?” (1 yes, 2 no)
NPSCL:
“Is medial temporal sclerosis (including hippocampal sclerosis) present?” (1 yes, 0 no)
NPTHPRIM=11:
“What is the primary neuropathological diagnostic classification?” (11=Hippocampal sclerosis)
NPTHSECN=11:
“What is the secondary neuropathological diagnostic classification?” (11=Hippocampal sclerosis)
Exclusions from either cases with pathologically confirmed dementia-inducing disease
# excludedNPFTD=1 or 2 / 74
NPTAU=1 / 56
NPPROG=1 / 17
NPPFTLD=1 / 6
NPPRION=1 / 1
NPPRNP=1 / 28
NPFTDNO=1 / 6
For reference to the NACC coding guidebook see:
Additional statistical analyses (including p values) for Fig. 3
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[2,]), gene.names = c("GRN"))
GRN (rs5848 T-) genotype only
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 0.6318271 1.640947 4.26178 0.05 186 199 385 0.3091134 GRN
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[3,]), gene.names = c("TMEM"))
TMEM106B (rs1990622 A-) genotype only
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 0.7548291 1.687778 3.773827 0.05 186 856 1042 0.20235 TMEM
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[4,]), gene.names = c("GRN TMEM"))
TMEM106B and GRN genotypes
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 1.228428 2.71555 6.002965 0.05 186 750 936 0.01357604 GRN TMEM
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[5,]), gene.names = c("ABCC9"))
ABCC9 (rs704180 A-A) genotype only
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 0.5457825 1.775794 5.777838 0.05 186 77 263 0.340087 ABCC9
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[6,]), gene.names = c("ABCC9 GRN"))
ABCC9 and GRN genotypes
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 1.602093 4.512605 12.71062 0.05 186 60 246 0.004344608 ABCC9 GRN
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[7,]), gene.names = c("ABCC9 TMEM"))
ABCC9 and TMEM106B genotypes
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 1.763477 3.995536 9.052745 0.05 186 333 519 0.0009021385 ABCC9 TMEM
> oddsratioWald.proc (cell.counts=c(ftab[1,],ftab[8,]), gene.names = c("ALL"))
All three genotypes (ABCC9, TMEM106B, and GRN)
LowerCI OR UpperCI alpha nRef nComp nTotal pValue genes
1 1.449222 3.386171 7.911936 0.05 186 248 434 0.004850008 ALL
Additional Acknowledgments
ADGC Acknowledgments (contributors)
Marilyn S. Albert1, Roger L. Albin2-4, Liana G. Apostolova5, Steven E. Arnold6, Sanjay Asthana7-9, Craig S. Atwood7,9, Clinton T. Baldwin10, Robert Barber11, Michael M. Barmada12, Lisa L. Barnes13,14, Thomas G. Beach15, James T. Becker16, Gary W. Beecham17,18, Duane Beekly19, Eileen H. Bigio20,21, Thomas D. Bird22,23, Deborah Blacker24,25, James D. Bowen27, Adam Boxer28, James R. Burke29, Joseph D. Buxbaum30-32, Nigel J. Cairns33, Laura B. Cantwell34, Chuanhai Cao35, Chris S. Carlson36, Cynthia M. Carlsson8, Regina M. Carney37, Steven L. Carroll39, Helena C. Chui40, David G. Clark41, David H. Cribbs44, Elizabeth A. Crocco37, Carlos Cruchaga45, Charles DeCarli46, Steven T. DeKosky47, F. Yesim Demirci12, Malcolm Dick48, Dennis W. Dickson38, Ranjan Duara49, Nilufer Ertekin-Taner38,50, Kelley M. Faber51, Kenneth B. Fallon39, Martin R. Farlow52, Steven Ferris53, Tatiana M. Foroud51, Matthew P. Frosch54, Douglas R. Galasko55, Mary Ganguli56, Daniel H. Geschwind57, Bernardino Ghetti58, John R. Gilbert17,18, Jonathan D. Glass59, Alison M. Goate45, Neill R. Graff-Radford38,50, John H. Growdon60, Hakon Hakonarson61, Ronald L. Hamilton62, Kara L. Hamilton-Nelson17, Lindy E. Harrell41, Elizabeth Head63, Lawrence S. Honig64, Christine M. Hulette65, Bradley T. Hyman60, Gail P. Jarvik66,67, Lee-Way Jin68, Gyungah Jun10,69,70, Anna Karydas28, John S.K. Kauwe72, Jeffrey A. Kaye73,74, Ronald Kim75, Edward H. Koo55, Neil W. Kowall76,77, Joel H. Kramer78, Brian W. Kunkle17, Frank M. LaFerla79, James J. Lah59, James B. Leverenz80, Allan I. Levey59, Ge Li81, Andrew P. Lieberman82, Chiao-Feng Lin34, Oscar L. Lopez71, Kathryn L. Lunetta69, Constantine G. Lyketsos83, Wendy J. Mack84, Daniel C. Marson41, Eden R. Martin17,18, Frank Martiniuk85, Deborah C. Mash86, Eliezer Masliah55,87, Wayne C. McCormick43, Susan M. McCurry88, Andrew N. McDavid36, Ann C. McKee76,77, Marsel Mesulam21,89, Bruce L. Miller28, Carol A. Miller90, Joshua W. Miller68, John C. Morris33,91, Jill R. Murrell51,58, Adam C. Naj34, John M. Olichney46, Joseph E. Parisi92, Henry L. Paulson2, William Perry17, Elaine Peskind81, Ronald C. Petersen26, Aimee Pierce44, Wayne W. Poon48, Huntington Potter35, Joseph F. Quinn73, Ashok Raj35, Murray Raskind81, Eric M. Reiman42,93,94, Barry Reisberg53,95, Christiane Reitz64,96,97, John M. Ringman5, Erik D. Roberson41, Howard J. Rosen28, Roger N. Rosenberg98, Mark A. Sager8, Mary Sano31, Andrew J. Saykin51,99, Lon S. Schneider40,100, William W. Seeley28, Amanda G. Smith35, Salvatore Spina58, Robert A. Stern76, Rudolph E. Tanzi60, Tricia A. Thornton-Wells101, John Q. Trojanowski34, Juan C. Troncoso102, Debby W. Tsuang23,81, Vivianna M. Van Deerlin34, Badri N. Vardarajan64,96,97, Harry V. Vinters5,103, Jean Paul Vonsattel104, Sandra Weintraub21,105, Kathleen A. Welsh-Bohmer29,106, Jennifer Williamson64, Sarah Wishnek17, Clinton B. Wright107, Steven G. Younkin38, Chang-En Yu43, Lei Yu13
Institutional Affiliations
1Department of Neurology, Johns Hopkins University, Baltimore, Maryland, 2Department of Neurology, University of Michigan, Ann Arbor, Michigan, 3Geriatric Research, Education and Clinical Center (GRECC), VA Ann Arbor Healthcare System (VAAAHS), Ann Arbor, Michigan, 4Michigan Alzheimer Disease Center, Ann Arbor, Michigan, 5Department of Neurology, University of California Los Angeles, Los Angeles, California, 6Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, 7Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, Wisconsin, 8Department of Medicine, University of Wisconsin, Madison, Wisconsin, 9Wisconsin Alzheimer's Institute, Madison, Wisconsin, 10Department of Medicine (Genetics Program), Boston University, Boston, Massachusetts, 11Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, 12Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, 13Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, 14Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, 15Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, Arizona, 16Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 17The John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, 18Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida, 19National Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, 20Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 21Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 22Department of Neurology, University of Washington, Seattle, Washington, 23VA Puget Sound Health Care System/GRECC, Seattle, Washington, 24Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, 25Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 26Department of Neurology, Mayo Clinic, Rochester, Minnesota, 27Swedish Medical Center, Seattle, Washington, 28Department of Neurology, University of California San Francisco, San Francisco, California, 29Department of Medicine, Duke University, Durham, North Carolina, 30Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, 31Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, 32Departments of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, 33Department of Pathology and Immunology, Washington University, St. Louis, Missouri, 34Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, 35USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, Florida, 36Fred Hutchinson Cancer Research Center, Seattle, Washington, 37Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida, 38Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, 39Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, 40Department of Neurology, University of Southern California, Los Angeles, California, 41Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, 42Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, 43Department of Medicine, University of Washington, Seattle, Washington, 44Department of Neurology, University of California Irvine, Irvine, California, 45Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, Missouri, 46Department of Neurology, University of California Davis, Sacramento, California, 47University of Virginia School of Medicine, Charlottesville, Virginia, 48Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, 49Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida, 50Department of Neurology, Mayo Clinic, Jacksonville, Florida, 51Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, 52Department of Neurology, Indiana University, Indianapolis, Indiana, 53Department of Psychiatry, New York University, New York, New York, 54C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, Massachusetts, 55Department of Neurosciences, University of California San Diego, La Jolla, California, 56Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, 57Neurogenetics Program, University of California Los Angeles, Los Angeles, California, 58Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana, 59Department of Neurology, Emory University, Atlanta, Georgia, 60Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 61Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 62Department of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, Pennsylvania, 63Sanders-Brown Center on Aging, Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, 64Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, 65Department of Pathology, Duke University, Durham, North Carolina, 66Department of Genome Sciences, University of Washington, Seattle, Washington, 67Department of Medicine (Medical Genetics), University of Washington, Seattle, Washington, 68Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, California, 69Department of Biostatistics, Boston University, Boston, Massachusetts, 70Department of Ophthalmology, Boston University, Boston, Massachusetts, 71University of Pittsburgh Alheimer's Disease Research Center, Pittsburgh, Pennsylvania, 72Department of Biology, Brigham Young University, Provo, Utah, 73Department of Neurology, Oregon Health & Science University, Portland, Oregon, 74Department of Neurology, Portland Veterans Affairs Medical Center, Portland, Oregon, 75Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California, 76Department of Neurology, Boston University, Boston, Massachusetts, 77Department of Pathology, Boston University, Boston, Massachusetts, 78Department of Neuropsychology, University of California San Francisco, San Francisco, California, 79Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, 80Department of Pathology, University of Washington, Seattle, Washington, 81Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, 82Department of Pathology, University of Michigan, Ann Arbor, Michigan, 83Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, 84Department of Preventive Medicine, University of Southern California, Los Angeles, California, 85Department of Medicine - Pulmonary, New York University, New York, New York, 86Department of Neurology, University of Miami, Miami, Florida, 87Department of Pathology, University of California San Diego, La Jolla, California, 88School of Nursing Northwest Research Group on Aging, University of Washington, Seattle, Washington, 89Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 90Department of Pathology, University of Southern California, Los Angeles, California, 91Department of Neurology, Washington University, St. Louis, Missouri, 92Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, 93Arizona Alzheimer’s Consortium, Phoenix, Arizona, 94Banner Alzheimer's Institute, Phoenix, Arizona, 95Alzheimer's Disease Center, New York University, New York, New York, 96Gertrude H. Sergievsky Center, Columbia University, New York, New York, 97Department of Neurology, Columbia University, New York, New York, 98Department of Neurology, University of Texas Southwestern, Dallas, Texas, 99Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, Indiana, 100Department of Psychiatry, University of Southern California, Los Angeles, California, 101Center for Human Genetics and Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, 102Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 103Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles, California, 104Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Pathology, Columbia University, New York, New York, 105Department of Psychiatry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 106Department of Psychiatry & Behavioral Sciences, Duke University, Durham, North Carolina, 107Evelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida
ADGC Acknowledgments (Funding)
The National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; P01 AG030128, NIA LOAD, U24 AG026395, U24 AG026390; Banner Sun Health Research Institute P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant # NS39764, NIMH MH60451 and by Glaxo Smith Kline. Samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors, including the Alzheimer’s Disease Centers who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. Support was also from the Alzheimer’s Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. We thank Drs. D. Stephen Snyder and Marilyn Miller from NIA who are ex-officio ADGC members.