0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Contributions |

A Comprehensive Genetic Association Study of Alzheimer Disease in African Americans

Mark W. Logue, PhD; Matthew Schu, MS; Badri N. Vardarajan, MS; Jacki Buros, BA; Robert C. Green, MD, MPH; Rodney C. P. Go, PhD; Patrick Griffith, MD; Thomas O. Obisesan, MD; Rhonna Shatz, MD; Amy Borenstein, PhD; L. Adrienne Cupples, PhD; Kathryn L. Lunetta, PhD; M. Daniele Fallin, PhD; Clinton T. Baldwin, PhD; Lindsay A. Farrer, PhD; for the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study Group
Arch Neurol. 2011;68(12):1569-1579. doi:10.1001/archneurol.2011.646.
Text Size: A A A
Published online

Objectives To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites.

Design We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population.

Subjects Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects.

Setting Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study.

Results Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P = .0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes.

Conclusions Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Association and linkage disequilibrium in the apolipoprotein E (APOE) region. A and B, Unadjusted findings in African Americans and whites, respectively; C and D, APOE -genotype adjusted findings in African Americans and whites, respectively. APOC1 indicates apolipoprotein C-I; Mb, megabase; PVRL2, poliovirus receptor–related 2; and TOMM40, translocase of outer mitochondrial membrane 40 yeast homologue.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Linkage disequilibrium in the apolipoprotein E (APOE) region. A, African American cohort data sets. B, White cohort data sets. Other gene names are described in the legend to Figure 1.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Manhattan plot of genome-wide association study results for the meta-analysis of the African American cohorts. The dotted line indicates suggestive evidence of association (P < 10−5).

Tables

References

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Clinical Scenario

brightcove.createExperiences();