Genetic influences on plasma homocysteine levels in African Americans and Yoruba Nigerians

Sungeun Kim, Kwangsik Nho, Vijay K. Ramanan, Dongbing Lai, Tatiana Foroud, Katie Lane, Jill R. Murrell, Sujuan Gao, Kathleen Hall, Frederick Unverzagt, Olusegun Baiyewu, Adesola Ogunniyi, Oye Gureje, Mitchel A. Kling, P. Murali Doraiswamy, Rima Kaddurah-Daouk, Hugh Hendrie, Andrew Saykin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Plasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer's disease (AD) and other dementias. A better understanding of the genetic factors regulating homocysteine levels, particularly in non-white populations, may help in risk stratification analyses of existing clinical trials and may point to novel targets for homocysteine-lowering therapy. To identify genetic influences on plasma homocysteine levels in individuals with African ancestry, we performed a targeted gene and pathway-based analysis using a priori biological information and then to identify new association performed a genome-wide association study. All analyses used combined data from the African American and Yoruba cohorts from the Indianapolis-Ibadan Dementia Project. Targeted analyses demonstrated significant associations of homocysteine and variants within the CBS (Cystathionine beta-Synthase) gene. We identified a novel genome-wide significant association of the AD risk gene CD2AP (CD2-associated protein) with plasma homocysteine levels in both cohorts. Minor allele (T) carriers of identified CD2AP variant (rs6940729) exhibited decreased homocysteine level. Pathway enrichment analysis identified several interesting pathways including the GABA receptor activation pathway. This is noteworthy given the known antagonistic effect of homocysteine on GABA receptors. These findings identify several new targets warranting further investigation in relation to the role of homocysteine in neurodegeneration.

Original languageEnglish (US)
Pages (from-to)991-1003
Number of pages13
JournalJournal of Alzheimer's Disease
Volume49
Issue number4
DOIs
StatePublished - Dec 24 2015

Fingerprint

Homocysteine
African Americans
GABA Receptors
Dementia
Alzheimer Disease
Cystathionine beta-Synthase
Genes
Genome-Wide Association Study
Cognition
Methylation
Alleles
Clinical Trials
Genome
Health

Keywords

  • African Continental Ancestry Group
  • CD2-associated protein
  • cystathionine beta-synthase
  • genome-wide association study
  • homocysteine
  • metabolic networks and pathways
  • metabolomics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Genetic influences on plasma homocysteine levels in African Americans and Yoruba Nigerians. / Kim, Sungeun; Nho, Kwangsik; Ramanan, Vijay K.; Lai, Dongbing; Foroud, Tatiana; Lane, Katie; Murrell, Jill R.; Gao, Sujuan; Hall, Kathleen; Unverzagt, Frederick; Baiyewu, Olusegun; Ogunniyi, Adesola; Gureje, Oye; Kling, Mitchel A.; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Hendrie, Hugh; Saykin, Andrew.

In: Journal of Alzheimer's Disease, Vol. 49, No. 4, 24.12.2015, p. 991-1003.

Research output: Contribution to journalArticle

Kim, S, Nho, K, Ramanan, VK, Lai, D, Foroud, T, Lane, K, Murrell, JR, Gao, S, Hall, K, Unverzagt, F, Baiyewu, O, Ogunniyi, A, Gureje, O, Kling, MA, Doraiswamy, PM, Kaddurah-Daouk, R, Hendrie, H & Saykin, A 2015, 'Genetic influences on plasma homocysteine levels in African Americans and Yoruba Nigerians', Journal of Alzheimer's Disease, vol. 49, no. 4, pp. 991-1003. https://doi.org/10.3233/JAD-150651
Kim, Sungeun ; Nho, Kwangsik ; Ramanan, Vijay K. ; Lai, Dongbing ; Foroud, Tatiana ; Lane, Katie ; Murrell, Jill R. ; Gao, Sujuan ; Hall, Kathleen ; Unverzagt, Frederick ; Baiyewu, Olusegun ; Ogunniyi, Adesola ; Gureje, Oye ; Kling, Mitchel A. ; Doraiswamy, P. Murali ; Kaddurah-Daouk, Rima ; Hendrie, Hugh ; Saykin, Andrew. / Genetic influences on plasma homocysteine levels in African Americans and Yoruba Nigerians. In: Journal of Alzheimer's Disease. 2015 ; Vol. 49, No. 4. pp. 991-1003.
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AU - Lane, Katie

AU - Murrell, Jill R.

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AU - Hall, Kathleen

AU - Unverzagt, Frederick

AU - Baiyewu, Olusegun

AU - Ogunniyi, Adesola

AU - Gureje, Oye

AU - Kling, Mitchel A.

AU - Doraiswamy, P. Murali

AU - Kaddurah-Daouk, Rima

AU - Hendrie, Hugh

AU - Saykin, Andrew

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