Genetic architecture of age-related cognitive decline in African Americans

Towfique Raj; Lori B. Chibnik; Cristin McCabe; Andus Wong; Joseph M. Replogle; Lei Yu; Sujuan Gao; Frederick W. Unverzagt; Barbara Stranger; Jill Murrell; Lisa Barnes; Hugh C. Hendrie; Tatiana Foroud; Anna Krichevsky; David A. Bennett; Kathleen S. Hall; Denis A. Evans; Philip L. De Jager

doi:10.1212/NXG.0000000000000125

Genetic architecture of age-related cognitive decline in African Americans

Towfique Raj, Lori B. Chibnik, Cristin McCabe, Andus Wong, Joseph M. Replogle, Lei Yu, Sujuan Gao, Frederick W. Unverzagt, Barbara Stranger, Jill Murrell, Lisa Barnes, Hugh C. Hendrie, Tatiana Foroud, Anna Krichevsky, David A. Bennett, Kathleen S. Hall, Denis A. Evans, Philip L. De Jager

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Abstract

Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

Original language	English
Article number	e125
Journal	Neurology: Genetics
Volume	3
Issue number	1
DOIs	https://doi.org/10.1212/NXG.0000000000000125
State	Published - 2016

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Raj, T., Chibnik, L. B., McCabe, C., Wong, A., Replogle, J. M., Yu, L., Gao, S., Unverzagt, F. W., Stranger, B., Murrell, J., Barnes, L., Hendrie, H. C., Foroud, T., Krichevsky, A., Bennett, D. A., Hall, K. S., Evans, D. A., & De Jager, P. L. (2016). Genetic architecture of age-related cognitive decline in African Americans. Neurology: Genetics, 3(1), Article e125. https://doi.org/10.1212/NXG.0000000000000125

@article{884363c8e43e4afe88601b07308dbd20,

title = "Genetic architecture of age-related cognitive decline in African Americans",

abstract = "Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.",

author = "Towfique Raj and Chibnik, {Lori B.} and Cristin McCabe and Andus Wong and Replogle, {Joseph M.} and Lei Yu and Sujuan Gao and Unverzagt, {Frederick W.} and Barbara Stranger and Jill Murrell and Lisa Barnes and Hendrie, {Hugh C.} and Tatiana Foroud and Anna Krichevsky and Bennett, {David A.} and Hall, {Kathleen S.} and Evans, {Denis A.} and {De Jager}, {Philip L.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2016",

doi = "10.1212/NXG.0000000000000125",

language = "English",

volume = "3",

journal = "Neurology: Genetics",

issn = "2376-7839",

publisher = "Lippincott Williams and Wilkins",

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Raj, T, Chibnik, LB, McCabe, C, Wong, A, Replogle, JM, Yu, L, Gao, S, Unverzagt, FW, Stranger, B, Murrell, J, Barnes, L, Hendrie, HC, Foroud, T, Krichevsky, A, Bennett, DA, Hall, KS, Evans, DA & De Jager, PL 2016, 'Genetic architecture of age-related cognitive decline in African Americans', Neurology: Genetics, vol. 3, no. 1, e125. https://doi.org/10.1212/NXG.0000000000000125

TY - JOUR

T1 - Genetic architecture of age-related cognitive decline in African Americans

AU - Raj, Towfique

AU - Chibnik, Lori B.

AU - McCabe, Cristin

AU - Wong, Andus

AU - Replogle, Joseph M.

AU - Yu, Lei

AU - Gao, Sujuan

AU - Unverzagt, Frederick W.

AU - Stranger, Barbara

AU - Murrell, Jill

AU - Barnes, Lisa

AU - Hendrie, Hugh C.

AU - Foroud, Tatiana

AU - Krichevsky, Anna

AU - Bennett, David A.

AU - Hall, Kathleen S.

AU - Evans, Denis A.

AU - De Jager, Philip L.

PY - 2016

Y1 - 2016

N2 - Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

AB - Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

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U2 - 10.1212/NXG.0000000000000125

DO - 10.1212/NXG.0000000000000125

M3 - Article

AN - SCOPUS:85052667779

SN - 2376-7839

VL - 3

JO - Neurology: Genetics

JF - Neurology: Genetics

IS - 1

M1 - e125

ER -

Genetic architecture of age-related cognitive decline in African Americans

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