. 2018 Dec;136(6):857-872.

doi: 10.1007/s00401-018-1881-4. Epub 2018 Jul 2.

Sex-specific genetic predictors of Alzheimer's disease biomarkers

Yuetiva Deming¹, Logan Dumitrescu², Lisa L Barnes³, Madhav Thambisetty⁴, Brian Kunkle⁵, Katherine A Gifford², William S Bush⁵, Lori B Chibnik^{6

7}, Shubhabrata Mukherjee⁸, Philip L De Jager^{9

10}, Walter Kukull¹¹, Matt Huentelman¹², Paul K Crane⁸, Susan M Resnick⁴, C Dirk Keene¹³, Thomas J Montine¹⁴, Gerard D Schellenberg¹⁵, Jonathan L Haines⁵, Henrik Zetterberg^{16

17

18

19}, Kaj Blennow^{16

17}, Eric B Larson^{8

20}, Sterling C Johnson^{21

22}, Marilyn Albert²³, Abhay Moghekar²³, Jorge L Del Aguila¹, Maria Victoria Fernandez¹, John Budde¹, Jason Hassenstab¹, Anne M Fagan²⁴, Matthias Riemenschneider²⁵, Ronald C Petersen²⁶, Lennart Minthon²⁷, Michael J Chao²⁸, Vivianna M Van Deerlin²⁹, Virginia M-Y Lee²⁹, Leslie M Shaw²⁹, John Q Trojanowski²⁹, Elaine R Peskind³⁰, Gail Li^{30

31}, Lea K Davis³², Julia M Sealock³², Nancy J Cox³²; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Genetics Consortium (ADGC); Alison M Goate²⁸, David A Bennett³, Julie A Schneider³, Angela L Jefferson², Carlos Cruchaga¹, Timothy J Hohman³³

Collaborators, Affiliations

Collaborators

Michael W Weiner, Ron Petersen, Paul Aisen, Clifford Jack, William Jagust, Leslie M Shaw, John Trojanowski, Laurel Beckett, Art Toga, Andrew Saykin, John C Morris, Tom Montine, Robert Green, Erin Abner, Perrie Adams, Marilyn Albert, Roger Albin, Liana Apostolova, Steven Arnold, Sanjay Asthana, Craig Atwood, Clinton Baldwin, Robert Barber, Lisa Barnes, Sandra Barral, Thomas Beach, James Becker, Gary Beecham, Duane Beekly, David Bennett, Eileen Bigio, Thomas Bird, Deborah Blacker, Bradley Boeve, James Bowen, Adam Boxer, James Burke, Jeffrey Burns, Joseph Buxbaum, Nigel Cairns, Laura Cantwell, Chuanhai Cao, Chris Carlson, Cynthia Carlsson, Regina Carney, Minerva Carrasquillo, Helena Chui, Paul Crane, David Cribbs, Elizabeth Crocco, Carlos Cruchaga, Philip De Jager, Charles DeCarli, Malcolm Dick, Dennis Dickson, Rachelle Doody, Ranjan Duara, Nilufer Ertekin-Taner, Denis Evans, Kelley Faber, Thomas Fairchild, Kenneth Fallon, David Fardo, Martin Farlow, Lindsay Farrer, Steven Ferris, Tatiana Foroud, Matthew Frosch, Douglas Galasko, Marla Gearing, Daniel Geschwind, Bernardino Ghetti, John Gilbert, Alison Goate, Neill Graff-Radford, Robert Green, John Growdon, Jonathan Haines, Hakon Hakonarson, Ronald Hamilton, Kara Hamilton-Nelson, John Hardy, Lindy Harrell, Lawrence Honig, Ryan Huebinger, Matthew Huentelman, Christine Hulette, Bradley Hyman, Gail Jarvik, Lee-Way Jin, Gyungah Jun, M Ilyas Kamboh, Anna Karydas, Mindy Katz, John Kauwe, Jeffrey Kaye, C Dirk Keene, Ronald Kim, Neil Kowall, Joel Kramer, Walter Kukull, Brian Kunkle, Amanda Kuzma, Frank LaFerla, James Lah, Eric Larson, James Leverenz, Allan Levey, Ge Li, Andrew Lieberman, Richard Lipton, Oscar Lopez, Kathryn Lunetta, Constantine Lyketsos, John Malamon, Daniel Marson, Eden Martin, Frank Martiniuk, Deborah Mash, Eliezer Masliah, Richard Mayeux, Wayne McCormick, Susan McCurry, Andrew McDavid, Stefan McDonough, Ann McKee, Marsel Mesulam, Bruce Miller, Carol Miller, Joshua Miller, Thomas Montine, John Morris, Shubhabrata Mukherjee, Amanda Myers, Adam Naj, Sid O'Bryant, John Olichney, Joseph Parisi, Henry Paulson, Margaret Pericak-Vance, Elaine Peskind, Ronald Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Liming Qu, Joseph Quinn, Ashok Raj, Murray Raskind, Eric Reiman, Barry Reisberg, Joan Reisch, Christiane Reitz, John Ringman, Erik Roberson, Ekaterina Rogaeva, Howard Rosen, Roger Rosenberg, Donald Royall, Mark Sager, Mary Sano, Andrew Saykin, Gerard Schellenberg, Julie Schneider, Lon Schneider, William Seeley, Amanda Smith, Joshua Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert Stern, Russell Swerdlow, Rudolph Tanzi, John Trojanowski, Juan Troncoso, Debby Tsuang, Otto Valladares, Vivianna Van Deerlin, Linda Van Eldik, Badri Vardarajan, Harry Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weintraub, Kathleen Welsh-Bohmer, Kirk Wilhelmsen, Jennifer Williamson, Thomas Wingo, Randall Woltjer, Clinton Wright, Chuang-Kuo Wu, Steven Younkin, Chang-En Yu, Lei Yu, Yi Zhao

Affiliations

¹ Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave. B8134, St. Louis, MO, 63110, USA.
² Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 1207 17th Avenue S, Nashville, TN, 37212, USA.
³ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁴ Unit of Clinical and Translational Neuroscience, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁵ Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁸ Department of Medicine, University of Washington, Seattle, WA, USA.
⁹ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
¹⁰ Cell Circuits Program, Broad Institute, Cambridge, MA, USA.
¹¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
¹² Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
¹³ Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁴ Department of Pathology, Stanford University, Stanford, CA, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
¹⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁸ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
¹⁹ UK Dementia Research Institute at UCL, London, UK.
²⁰ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
²¹ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²² Geriatric Research Education and Clinical Center of the Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA.
²³ Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁴ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
²⁵ Clinic of Psychiatry and Psychotherapy, Saarland University, Homburg/Saar, Germany.
²⁶ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
²⁷ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
²⁸ Ronald M Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³⁰ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
³¹ Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
³² Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
³³ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 1207 17th Avenue S, Nashville, TN, 37212, USA. Timothy.J.Hohman@Vanderbilt.edu.

PMID: 29967939
PMCID: PMC6280657
DOI: 10.1007/s00401-018-1881-4

Sex-specific genetic predictors of Alzheimer's disease biomarkers

Yuetiva Deming et al. Acta Neuropathol. 2018 Dec.

. 2018 Dec;136(6):857-872.

doi: 10.1007/s00401-018-1881-4. Epub 2018 Jul 2.

Authors

Collaborators

Michael W Weiner, Ron Petersen, Paul Aisen, Clifford Jack, William Jagust, Leslie M Shaw, John Trojanowski, Laurel Beckett, Art Toga, Andrew Saykin, John C Morris, Tom Montine, Robert Green, Erin Abner, Perrie Adams, Marilyn Albert, Roger Albin, Liana Apostolova, Steven Arnold, Sanjay Asthana, Craig Atwood, Clinton Baldwin, Robert Barber, Lisa Barnes, Sandra Barral, Thomas Beach, James Becker, Gary Beecham, Duane Beekly, David Bennett, Eileen Bigio, Thomas Bird, Deborah Blacker, Bradley Boeve, James Bowen, Adam Boxer, James Burke, Jeffrey Burns, Joseph Buxbaum, Nigel Cairns, Laura Cantwell, Chuanhai Cao, Chris Carlson, Cynthia Carlsson, Regina Carney, Minerva Carrasquillo, Helena Chui, Paul Crane, David Cribbs, Elizabeth Crocco, Carlos Cruchaga, Philip De Jager, Charles DeCarli, Malcolm Dick, Dennis Dickson, Rachelle Doody, Ranjan Duara, Nilufer Ertekin-Taner, Denis Evans, Kelley Faber, Thomas Fairchild, Kenneth Fallon, David Fardo, Martin Farlow, Lindsay Farrer, Steven Ferris, Tatiana Foroud, Matthew Frosch, Douglas Galasko, Marla Gearing, Daniel Geschwind, Bernardino Ghetti, John Gilbert, Alison Goate, Neill Graff-Radford, Robert Green, John Growdon, Jonathan Haines, Hakon Hakonarson, Ronald Hamilton, Kara Hamilton-Nelson, John Hardy, Lindy Harrell, Lawrence Honig, Ryan Huebinger, Matthew Huentelman, Christine Hulette, Bradley Hyman, Gail Jarvik, Lee-Way Jin, Gyungah Jun, M Ilyas Kamboh, Anna Karydas, Mindy Katz, John Kauwe, Jeffrey Kaye, C Dirk Keene, Ronald Kim, Neil Kowall, Joel Kramer, Walter Kukull, Brian Kunkle, Amanda Kuzma, Frank LaFerla, James Lah, Eric Larson, James Leverenz, Allan Levey, Ge Li, Andrew Lieberman, Richard Lipton, Oscar Lopez, Kathryn Lunetta, Constantine Lyketsos, John Malamon, Daniel Marson, Eden Martin, Frank Martiniuk, Deborah Mash, Eliezer Masliah, Richard Mayeux, Wayne McCormick, Susan McCurry, Andrew McDavid, Stefan McDonough, Ann McKee, Marsel Mesulam, Bruce Miller, Carol Miller, Joshua Miller, Thomas Montine, John Morris, Shubhabrata Mukherjee, Amanda Myers, Adam Naj, Sid O'Bryant, John Olichney, Joseph Parisi, Henry Paulson, Margaret Pericak-Vance, Elaine Peskind, Ronald Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Liming Qu, Joseph Quinn, Ashok Raj, Murray Raskind, Eric Reiman, Barry Reisberg, Joan Reisch, Christiane Reitz, John Ringman, Erik Roberson, Ekaterina Rogaeva, Howard Rosen, Roger Rosenberg, Donald Royall, Mark Sager, Mary Sano, Andrew Saykin, Gerard Schellenberg, Julie Schneider, Lon Schneider, William Seeley, Amanda Smith, Joshua Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert Stern, Russell Swerdlow, Rudolph Tanzi, John Trojanowski, Juan Troncoso, Debby Tsuang, Otto Valladares, Vivianna Van Deerlin, Linda Van Eldik, Badri Vardarajan, Harry Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weintraub, Kathleen Welsh-Bohmer, Kirk Wilhelmsen, Jennifer Williamson, Thomas Wingo, Randall Woltjer, Clinton Wright, Chuang-Kuo Wu, Steven Younkin, Chang-En Yu, Lei Yu, Yi Zhao

Affiliations

¹ Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave. B8134, St. Louis, MO, 63110, USA.
² Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 1207 17th Avenue S, Nashville, TN, 37212, USA.
³ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁴ Unit of Clinical and Translational Neuroscience, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁵ Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁸ Department of Medicine, University of Washington, Seattle, WA, USA.
⁹ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
¹⁰ Cell Circuits Program, Broad Institute, Cambridge, MA, USA.
¹¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
¹² Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
¹³ Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁴ Department of Pathology, Stanford University, Stanford, CA, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
¹⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁸ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
¹⁹ UK Dementia Research Institute at UCL, London, UK.
²⁰ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
²¹ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²² Geriatric Research Education and Clinical Center of the Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA.
²³ Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁴ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
²⁵ Clinic of Psychiatry and Psychotherapy, Saarland University, Homburg/Saar, Germany.
²⁶ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
²⁷ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
²⁸ Ronald M Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³⁰ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
³¹ Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
³² Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
³³ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 1207 17th Avenue S, Nashville, TN, 37212, USA. Timothy.J.Hohman@Vanderbilt.edu.

PMID: 29967939
PMCID: PMC6280657
DOI: 10.1007/s00401-018-1881-4

Abstract

Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = - 0.03, p = 4.25 × 10^-8; β = 0.03, p = 3.97 × 10^-8) than males (β = - 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10^-10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (p_female = 0.047; p_male = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Keywords: APOE; Alzheimer disease; Amyloid; Cerebrospinal fluid biomarkers; Neuropathology; Sex difference; Tau.

PubMed Disclaimer

Conflict of interest statement

Competing Financial Interests

Figures

**Fig. 1. Sex-Stratified Genome-Wide Association Results for CSF Aβ42**
Miami plot illustrating CSF Aβ42 genome-wide association results stratified by males and females. Male findings are plotted in blue and grey on the top and female results are plotted in pink and grey at the bottom. The red lines at the top and bottom represent the genome-wide threshold for statistical significance (p<5×10⁻⁸).

**Fig. 2. Sex-Stratified Genome-Wide Association Results for CSF Tau**
Miami plot illustrating CSF total tau genome-wide association results stratified by males and females. Male findings are plotted in blue and grey on the top and female results are plotted in pink and grey at the bottom. The red lines at the top and bottom represent the genome-wide threshold for statistical significance (p<5×10⁻⁸).

**Fig. 3. Significant Sex-Specific Gene Expression Associations with Tangle Pathology Among Genes in the rs1393060 Locus**
**(a)** *OSTN* and **(b)** *CLDN16* expression in the prefrontal cortex are presented on the X-axis, square-root transformed neurofibrillary tangle burden (measured with immunohistochemistry) is presented on the Y-axis. Females are presented in red and males are presented in blue.

**Fig. 4. Significant Sex-Specific Gene Expression Association Between *SERPINB6* Expression in the Prefrontal Cortex and Amyloid Burden**
*SERPINB6* expression in the prefrontal cortex are presented on the X-axis, square-root transformed amyloid burden (measured with immunohistochemistry) is presented on the Y-axis. Females are presented in red and males are presented in blue. Individuals with an amyloid burden value of 0 in the figure did not show IHC evidence of amyloidosis at autopsy.

See this image and copyright information in PMC

References

1. Altmann A, Tian L, Henderson VW, Greicius MD, Alzheimer’s Disease Neuroimaging Initiative I (2014) Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol 75: 563–573 10.1002/ana.24135 - DOI - PMC - PubMed
1. Apostolova LG, Dinov ID, Dutton RA, Hayashi KM, Toga AW, Cummings JL, Thompson PM (2006) 3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer’s disease. Brain 129: 2867–2873 10.1093/brain/awl274 - DOI - PubMed
1. Ataman B, Boulting GL, Harmin DA, Yang MG, Baker-Salisbury M, Yap EL, Malik AN, Mei K, Rubin AA, Spiegel I et al. (2016) Evolution of Osteocrin as an activity-regulated factor in the primate brain. Nature 539: 242–247 10.1038/nature20111 - DOI - PMC - PubMed
1. Barnes LL, Wilson RS, Bienias JL, Schneider JA, Evans DA, Bennett DA (2005) Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry 62: 685–691 10.1001/archpsyc.62.6.685 - DOI - PubMed
1. Bennett DA, Schneider JA, Arvanitakis Z, Wilson RS (2012) Overview and findings from the religious orders study. Curr Alzheimer Res 9: 628–645 - PMC - PubMed

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Sex-specific genetic predictors of Alzheimer's disease biomarkers

Collaborators

Affiliations

Sex-specific genetic predictors of Alzheimer's disease biomarkers

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Grants and funding

LinkOut - more resources

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