Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans

Summary: Researchers have discovered two genetic risk factors for Alzheimer’s disease among African Americans.

Source: Boston University Medical Center.

Researchers have identified two new genetic risk factors for Alzheimer’s disease (AD) among African Americans.

The findings, which appear online in the journal Alzheimer’s and Dementia, may lead to the development of new therapies specifically targeting those genes.

Despite the fact that AD is more common in African Americans than Caucasians, the AD genetic risk profile for African Americans is more poorly understood. While more than 20 genes have been identified as risk factors for AD in Caucasians, fewer than five have been identified for African Americans.

In 2013, a genome-wide association study of AD in more than 5,500 African Americans identified two genetic risk factors for AD. This study looked at genetic variants across subjects’ entire genome and compared their frequency in cases versus controls. Researchers from Boston University School of Medicine (BUSM) used these same subjects, but added additional AD risk information (smoking status, diabetes status, education level) to their statistical modeling to increase the power of the study. By doing so they were able to identify two new genes (COBL and SLC10A2) associated with risk of AD in African Americans.

“There are currently no medications for AD that slow or stop the progression of the disease. Genes that increase risk for AD are potential targets for new disease-modifying AD drug therapies. Our study identifies two potentially “drugable” targets,” explains corresponding author Jesse Mez, MD, MS, assistant professor of neurology at BUSM and associate director of the Boston University Alzheimer’s Disease & CTE Center Clinical Core.

Image shows a dna strand.
In 2013, a genome-wide association study of AD in more than 5,500 African Americans identified two genetic risk factors for AD. NeuroscienceNews.com image is in the public domain.

According to the researchers the methodology they employed for this study allowed them to make an important discovery without investing more money in genotyping or more effort to recruit volunteers. They believe the a similar methodology could be used for many other diseases to make new genetic discoveries without new large investments.

“Despite the fact that Alzheimer’s disease is more common in African Americans than Caucasians, we understand less about the genes that influence risk of Alzheimer’s in African Americans. Our hope is that this study begins to eliminate that disparity and that ultimately these newly identified genes become targets for Alzheimer’s disease drug development,” added Mez.

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Source: Gina DiGravio – Boston University Medical Center
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans” by Jesse Mez, Jaeyoon Chung, Gyungah Jun, Joshua Kriegel, Alexandra P. Bourlas, Richard Sherva, Mark W. Logue, Lisa L. Barnes, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Paul K. Crane, Nilüfer Ertekin-Taner, Denis Evans, M. Daniele Fallin, Tatiana Foroud, Alison Goate, Neill R. Graff-Radford, Kathleen S. Hall, M. Ilyas Kamboh, Walter A. Kukull, Eric B. Larson, Jennifer J. Manly, Alzheimer Disease Genetics Consortium, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Kathryn L. Lunetta, and Lindsay A. Farrer in Alzheimer’s & Dementia. Published online October 19 2016 doi:10.1016/j.jalz.2016.09.002

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[cbtabs][cbtab title=”MLA”]Boston University Medical Center “Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans.” NeuroscienceNews. NeuroscienceNews, 25 October 2016.
<https://neurosciencenews.com/genetics-african-american-alzheimers-5346/>.[/cbtab][cbtab title=”APA”]Boston University Medical Center (2016, October 25). Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans. NeuroscienceNew. Retrieved October 25, 2016 from https://neurosciencenews.com/genetics-african-american-alzheimers-5346/[/cbtab][cbtab title=”Chicago”]Boston University Medical Center “Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans.” https://neurosciencenews.com/genetics-african-american-alzheimers-5346/ (accessed October 25, 2016).[/cbtab][/cbtabs]


Abstract

Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans

Introduction
African Americans’ (AAs) late-onset Alzheimer’s disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.

Methods
We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.

Results
Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability.

Discussion

An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

“Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans” by Jesse Mez, Jaeyoon Chung, Gyungah Jun, Joshua Kriegel, Alexandra P. Bourlas, Richard Sherva, Mark W. Logue, Lisa L. Barnes, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Paul K. Crane, Nilüfer Ertekin-Taner, Denis Evans, M. Daniele Fallin, Tatiana Foroud, Alison Goate, Neill R. Graff-Radford, Kathleen S. Hall, M. Ilyas Kamboh, Walter A. Kukull, Eric B. Larson, Jennifer J. Manly, Alzheimer Disease Genetics Consortium, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Kathryn L. Lunetta, and Lindsay A. Farrer in Alzheimer’s & Dementia. Published online October 19 2016 doi:10.1016/j.jalz.2016.09.002

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