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Follow Up Study Description

ADSP Follow-up Study (FUS)

Last Updated 5/11/18. PDF

A majority of the samples from the ADSP discovery phase are non-Hispanic white (NHW) in origin, making the addition of ethnically diverse samples to the study critical to identification of both shared and novel genetic risk factors for Alzheimer’s disease (AD) between populations. Collection and sequencing of ethnic diversity is emphasized in the  ‘ADSP Follow-Up Study (FUS) Phase’ with its directive that additional existing cohorts with unrelated AD cases that ‘encompass the richest possible ethnic diversity’ be given the highest priority for inclusion.

To fulfill the goals of this FUS Phase Mandate, eight existing elderly cohorts of African-American (AA) and pan-HI ancestry with a total of 13,745 samples (N=2,456 AA AD cases and 4,126 AA controls and 2,588 Hispanic AD cases and 4,475 Hispanic controls) are being whole genome sequenced (WGS) at Uniformed Services University of the Health Sciences (USUHS) in collaboration with existing NIH-funded AD infrastructure (NCRAD, NIAGADS, GCAD). 1,500 NHW autopsy cases and 1,372 controls are also being sequenced in order to increase a currently underpowered NHW sample with WGS. Brief descriptions of the cohorts selected for sequencing are provided below.

 

ADSP FUS Cohort Descriptions

The Alzheimer’s Disease Genetics Consortium (ADGC) African-American Cohort, is a cohort of 1,240 cases and 1,643 controls collected from several cohorts including from the GenerAAtions Study, Indianapolis-Ibadan Study, Rush University, University of Miami, Case Western Reserve University, North Carolina A & T University, and The Mirage Study.

The Mexican Health and Aging Study (MHAS) (http://www.mhasweb.org/index.aspx), sponsored by the National Institutes of Health (NIH) National Institute on Aging (NIA), is prospective study of health and aging in Mexico that began in 2001 (MHAS 2001). The ADSP FUS will sequence 200 MHAS cases and 2,600 MHAS controls from this study starting in 2019.

The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study (http://www.regardsstudy.org/), sponsored by the NIH’s National Institute for Neurological Disorders and Stroke (NINDS), is a national study of risk factors for stroke in adults 45 years or older that includes measurements of traditional stroke risk factors such as blood pressure and cholesterol levels, and an echocardiogram of the heart (Longstreth 2006). THE ADSP FUS will sequence 1,000 African-American cases and 1,500 African-American controls from this study starting in 2019.

The Northern Manhattan Study (NOMAS) (http://columbianomas.org/study/html), funded by the NIH’s NINDS, is a study focused on stroke or related neurological syndromes (Sacco et al. 2004). The ADSP FUS will sequence 88 Hispanic cases and 175 Hispanic controls, and 22 African-American cases and 43 African-American controls from this study starting in 2020.

The Puerto Rican 10/66 Study (https://www.alz.co.uk/1066/), is an Alzheimer’s Disease International study of dementia in Puerto Rico that began in 2007 (Prince et al. 2007). The ADSP FUS will sequence 1000 Puerto Rican cases and 1000 Puerto Rican controls from this study starting in 2018.

The Puerto Rican Alzheimer’s Disease Initiative (PRADI), a NIH NIA study of late-onset Alzheimer disease focused on the Caribbean-Hispanic Puerto Rican population. The ADSP FUS will sequence 500 cases and 500 controls from this study starting in 2020.

The Research in African-American Alzheimer’s Disease Initiative (REAAADI), a NIH NIA study focused on identifying genetic factors for Alzheimer disease within the African-American population in order to detect new targets for drug development and improve accessibility to Alzheimer’s disease education within the community. The ADSP FUS will sequence 300 cases and 300 controls from this study starting in 2020.

The Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) Study, a study of LOAD patients with Caribbean-Hispanic ancestry.  The ADSP FUS will sequence 800 cases and 300 controls from this study starting in 2019.

The Alzheimer’s Disease Center Autopsy (ADC) Cohort includes 1,500 cases with autopsy and 1,372 controls from the National Institute on Aging’s ADC’s (https://www.nia.nih.gov/health/alzheimers-disease-research-centers). These individuals are well phenotyped and will help to increase the currently underpowered NHW sample with WGS data from the ADSP Discovery and Discovery Extension Phases (1,212 cases and 524 controls).

 

References

Hendrie HC, Ch B MB, Osuntokun BO, et al. Prevalence of Alzheimer’s Disease and Dementia in Two Communities: Nigerian Africans and African Americans. Am J Psychiatry. 1995;152(10):1485-92. doi:10.1176/ajp.152.10.1485

Longstreth WT. The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study and the National Institute of Neurological Disorders and Stroke (NINDS). Stroke. 2006;37(5):1147-1147. doi:10.1161/01.STR.0000217259.92964.62.

MHAS. Data files and documentation (public use): Mexican Health and Ageing Study. http://www.mhasweb.org. Published 2001. Accessed July 20, 2017.

Mueller SG, Weiner MW, Thal LJ, et al. Ways toward an early diagnosis in Alzheimer’s disease: the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2005;1(1):55-66.

Prince M, Ferri CP, Acosta D, et al. The protocols for the 10/66 dementia research group population-based research programme. BMC Public Health. 2007;7(1):165. doi:10.1186/1471-2458-7-165.

Sacco RL, Anand K, Lee H-S, et al. Homocysteine and the Risk of Ischemic Stroke in a Triethnic Cohort: The Northern Manhattan Study. Stroke. 2004;35(10):2263-2269. doi:10.1161/01.STR.0000142374.33919.92.

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