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Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

Publication ,  Journal Article
Kim, S; Nho, K; Ramanan, VK; Lai, D; Foroud, TM; Lane, K; Murrell, JR; Gao, S; Hall, KS; Unverzagt, FW; Baiyewu, O; Ogunniyi, A; Gureje, O ...
Published in: J Alzheimers Dis
2016

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.

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Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2016

Volume

49

Issue

4

Start / End Page

991 / 1003

Location

United States

Related Subject Headings

  • Prospective Studies
  • Nigeria
  • Neurology & Neurosurgery
  • Male
  • Longitudinal Studies
  • Indiana
  • Humans
  • Homocysteine
  • Heterozygote
  • Genome-Wide Association Study
 

Citation

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Kim, S., Nho, K., Ramanan, V. K., Lai, D., Foroud, T. M., Lane, K., … Saykin, A. J. (2016). Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians. J Alzheimers Dis, 49(4), 991–1003. https://doi.org/10.3233/JAD-150651
Kim, Sungeun, Kwangsik Nho, Vijay K. Ramanan, Dongbing Lai, Tatiana M. Foroud, Katie Lane, Jill R. Murrell, et al. “Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.J Alzheimers Dis 49, no. 4 (2016): 991–1003. https://doi.org/10.3233/JAD-150651.
Kim S, Nho K, Ramanan VK, Lai D, Foroud TM, Lane K, et al. Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians. J Alzheimers Dis. 2016;49(4):991–1003.
Kim, Sungeun, et al. “Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.J Alzheimers Dis, vol. 49, no. 4, 2016, pp. 991–1003. Pubmed, doi:10.3233/JAD-150651.
Kim S, Nho K, Ramanan VK, Lai D, Foroud TM, Lane K, Murrell JR, Gao S, Hall KS, Unverzagt FW, Baiyewu O, Ogunniyi A, Gureje O, Kling MA, Doraiswamy PM, Kaddurah-Daouk R, Hendrie HC, Saykin AJ. Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians. J Alzheimers Dis. 2016;49(4):991–1003.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2016

Volume

49

Issue

4

Start / End Page

991 / 1003

Location

United States

Related Subject Headings

  • Prospective Studies
  • Nigeria
  • Neurology & Neurosurgery
  • Male
  • Longitudinal Studies
  • Indiana
  • Humans
  • Homocysteine
  • Heterozygote
  • Genome-Wide Association Study