Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

Mark W. Logue; Matthew Schu; Badri N. Vardarajan; John Farrell; David A. Bennett; Joseph D. Buxbaum; Goldie S. Byrd; Nilufer Ertekin-Taner; Denis Evans; Tatiana Foroud; Alison Goate; Neill R. Graff-Radford; M. Ilyas Kamboh; Walter A. Kukull; Jennifer J. Manly; Jonathan L. Hainesm; Richard Mayeuxl; Margaret A. Pericak-Vancen; Gerard D. Schellenbergo; Kathryn L. Lunettab; Clinton T. Baldwina; M. Daniele Fallinp; Lindsay A. Farrer

doi:10.1016/j.jalz.2014.06.010

Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

Mark W. Logue, Matthew Schu, Badri N. Vardarajan, John Farrell, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Nilufer Ertekin-Taner, Denis Evans, Tatiana Foroud, Alison Goate, Neill R. Graff-Radford, M. Ilyas Kamboh, Walter A. Kukull, Jennifer J. Manly, Jonathan L. Hainesm, Richard Mayeuxl, Margaret A. Pericak-Vancen, Gerard D. Schellenbergo, Kathryn L. LunettabClinton T. Baldwina, M. Daniele Fallinp, Lindsay A. Farrer

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

Background Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites. Methods Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC). Results Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P <.05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P =.014) and rs149979685 (P =.037). These associations were replicated in the ADGC sample (rs144662445: P =.0022, odds ratio [OR] = 2.75; rs149979685: P =.0022, OR = 3.61). Conclusions Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.

Original language	English (US)
Pages (from-to)	609-618.e11
Journal	Alzheimer's and Dementia
Volume	10
Issue number	6
DOIs	https://doi.org/10.1016/j.jalz.2014.06.010
State	Published - Nov 1 2014

Keywords

AKAP9
African American
Genetic association
Late-onset Alzheimer's disease
Rare variant
Whole-exome sequencing

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1016/j.jalz.2014.06.010

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Logue, M. W., Schu, M., Vardarajan, B. N., Farrell, J., Bennett, D. A., Buxbaum, J. D., Byrd, G. S., Ertekin-Taner, N., Evans, D., Foroud, T., Goate, A., Graff-Radford, N. R., Kamboh, M. I., Kukull, W. A., Manly, J. J., Hainesm, J. L., Mayeuxl, R., Pericak-Vancen, M. A., Schellenbergo, G. D., ... Farrer, L. A. (2014). Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans. Alzheimer's and Dementia, 10(6), 609-618.e11. https://doi.org/10.1016/j.jalz.2014.06.010

Logue, MW, Schu, M, Vardarajan, BN, Farrell, J, Bennett, DA, Buxbaum, JD, Byrd, GS, Ertekin-Taner, N, Evans, D, Foroud, T, Goate, A, Graff-Radford, NR, Kamboh, MI, Kukull, WA, Manly, JJ, Hainesm, JL, Mayeuxl, R, Pericak-Vancen, MA, Schellenbergo, GD, Lunettab, KL, Baldwina, CT, Daniele Fallinp, M & Farrer, LA 2014, 'Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans', Alzheimer's and Dementia, vol. 10, no. 6, pp. 609-618.e11. https://doi.org/10.1016/j.jalz.2014.06.010

@article{cf7d0e00b0b648dfa768fd1d61eb2dd5,

title = "Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans",

abstract = "Background Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites. Methods Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC). Results Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P <.05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P =.014) and rs149979685 (P =.037). These associations were replicated in the ADGC sample (rs144662445: P =.0022, odds ratio [OR] = 2.75; rs149979685: P =.0022, OR = 3.61). Conclusions Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.",

keywords = "AKAP9, African American, Genetic association, Late-onset Alzheimer's disease, Rare variant, Whole-exome sequencing",

author = "Logue, {Mark W.} and Matthew Schu and Vardarajan, {Badri N.} and John Farrell and Bennett, {David A.} and Buxbaum, {Joseph D.} and Byrd, {Goldie S.} and Nilufer Ertekin-Taner and Denis Evans and Tatiana Foroud and Alison Goate and Graff-Radford, {Neill R.} and Kamboh, {M. Ilyas} and Kukull, {Walter A.} and Manly, {Jennifer J.} and Hainesm, {Jonathan L.} and Richard Mayeuxl and Pericak-Vancen, {Margaret A.} and Schellenbergo, {Gerard D.} and Lunettab, {Kathryn L.} and Baldwina, {Clinton T.} and {Daniele Fallinp}, M. and Farrer, {Lindsay A.}",

year = "2014",

month = nov,

day = "1",

doi = "10.1016/j.jalz.2014.06.010",

language = "English (US)",

volume = "10",

pages = "609--618.e11",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

AU - Logue, Mark W.

AU - Schu, Matthew

AU - Vardarajan, Badri N.

AU - Farrell, John

AU - Bennett, David A.

AU - Buxbaum, Joseph D.

AU - Byrd, Goldie S.

AU - Ertekin-Taner, Nilufer

AU - Evans, Denis

AU - Foroud, Tatiana

AU - Goate, Alison

AU - Graff-Radford, Neill R.

AU - Kamboh, M. Ilyas

AU - Kukull, Walter A.

AU - Manly, Jennifer J.

AU - Hainesm, Jonathan L.

AU - Mayeuxl, Richard

AU - Pericak-Vancen, Margaret A.

AU - Schellenbergo, Gerard D.

AU - Lunettab, Kathryn L.

AU - Baldwina, Clinton T.

AU - Daniele Fallinp, M.

AU - Farrer, Lindsay A.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Background Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites. Methods Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC). Results Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P <.05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P =.014) and rs149979685 (P =.037). These associations were replicated in the ADGC sample (rs144662445: P =.0022, odds ratio [OR] = 2.75; rs149979685: P =.0022, OR = 3.61). Conclusions Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.

AB - Background Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites. Methods Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC). Results Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P <.05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P =.014) and rs149979685 (P =.037). These associations were replicated in the ADGC sample (rs144662445: P =.0022, odds ratio [OR] = 2.75; rs149979685: P =.0022, OR = 3.61). Conclusions Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.

KW - AKAP9

KW - African American

KW - Genetic association

KW - Late-onset Alzheimer's disease

KW - Rare variant

KW - Whole-exome sequencing

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AN - SCOPUS:84927158295

SN - 1552-5260

VL - 10

SP - 609-618.e11

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

Abstract

Keywords

ASJC Scopus subject areas

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