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Univ. de Ciencias Medicas - Habana, Cuba Centro Nacional de Genetica, Havana,Cuba

“ Does African ancestry protect against dementia? A population-based case-control study in an admixed Cuban population ? . ”. Juan J. Llibre Rodriguez , Beatriz Macheco Teruel , Cleusa Ferris, Paul McKeigue, Martin J Prince. For and on behalf of 10/66. Univ. de Ciencias Medicas - Habana, Cuba

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Univ. de Ciencias Medicas - Habana, Cuba Centro Nacional de Genetica, Havana,Cuba

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  1. “Does African ancestry protect against dementia? A population-based case-control study in an admixed Cuban population? .” Juan J. Llibre Rodriguez , Beatriz Macheco Teruel , Cleusa Ferris, Paul McKeigue, Martin J Prince. For and on behalf of 10/66 Univ. de Ciencias Medicas - Habana, Cuba Centro Nacional de Genetica, Havana,Cuba Centre for Public Mental Health, KCL, UK

  2. Population 11,6 millons • Life expectancy • Men 79 years • Women 80 years • Dementia´s prevalence • 6.4-10.2 % (130 000 cases ) • Incidence rate 21.7 per • 1000/year (28 760 new • cases/year) • Mortality rate in dementia • people 195.5 per 1000/year

  3. Does African ancestry protect against dementia? A population-based case-control study in an admixed Cuban population? Admixtures mapping provides information about the contribution of genetic and non genetic factors. In Cuba, there is sufficient variation of admixture between individuals to detect relationships of disease risk to proportionate admixture.

  4. The US/ Nigeria study • Clear association between apoE e4 and AD in African Americans in Indianapolis, US • (Hendrie - Ann Neurol 1995) • No association between apoE e4 and AD in Yoruba in Ibadan, Nigeria • (Osontokun - Ann Neurol 1995)

  5. Prev. 30 (%) 25 20 Cuba - 10/66 15 Cuba - DSM IV EURODEM 10 5 0 65-69 70-74 75-79 80+ Age (years) Prevalence of dementia by age in Cuba Llibre Rodríguez J.J, Valhuerdi A., Sanchez I.I., Guerra M.A, Prince M, et al. “The prevalence, correlates and impact of dementia in Cuba”. Neuroepidemiology 2008;31:243–251.

  6. Incidence of dementia by sex and age, Cuba Cohort 65 years and over N=2728 * Incidence rate/ 1000 pyr

  7. Risk factors for incident dementia

  8. Main source of admixture Migration , 1400–1800,

  9. Design Populations of mixed African and Caucasian ancestry Genotype to measure ancestry directly in individuals Hypothesis Higher levels of African ancestry associated with lower risk of dementia 10/66 admixture studies

  10. The 10/66 protocol. • Door knocking • Cognitive test • Clinical interview • Socio-demographic and risk factor • interview • Physical/ neurological examination • Blood test • Informant interview • 10/66 Dementia diagnosis • DSM IV Dementia • DSM IV/ ICD10 Depression Esperanza Aged 104 years! Prince M, Ferri CP, Acosta D, et al. The protocols for the 10/66 Dementia Research Group population-based research programme. BMC Public Health 2007,7:165.

  11. Admixture and dementia 238 dementia cases 355 controls SNP studies (60 markers of admixture) APOE 4 in 2500 population samples

  12. Box plot of African admixture distribution by ethno-racial identity (weighted) ‘White’ “Mixed” Black’ Ethno racial group

  13. APOE Genotype by dementia status

  14. Cuba – association of APOE genotype with dementia * Adjusted age, sex and education

  15. Incidence of dementia according age group and APOE 4 genotype (HR). Cuba 10/66 incidence phase. *p<0.006

  16. APOE allele frequency by ethno-racial identity

  17. Mean admixture proportion by APOE allele status (case control subsample)

  18. Correlates of African admixture socio-culturally constructed? • Lower education • Lower socioeconomic status • More hazardous drinking genetically mediated? • Larger skulls and longer legs • Lower triglyceride • Higher ‘bad’ cholesterol (LDL, VLDL) • Lower ‘good’ cholesterol (HDL) • Higher e4 prevalence (but this does not mediate effect on lipids) • Higher systolic blood pressure • Increased risk of stroke - adjusted OR = 4.59 (1.09-19.3)

  19. Conclusions • No support for the hypotheses that genes linked to admixture may reduce the risk for dementia among Africans, or modify the effect of APOE genotype • We will be able to look at effect modification with more power with our other admixed samples • No evidence for population stratification in the estimation of the association between APOE and dementia • Important effect of African ancestry on risk for stroke • Potential to use admixture linkage analysis to identify genes linked to admixture responsible for this effect

  20. Alzheimer’s Disease International The 10/66 Dementia Research Group Our funders The Wellcome Trust Institute of Psychiatry London , UK BMC Medical Genetics 2011 My thanks to

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