Human Genetics

, Volume 127, Issue 6, pp 629–638 | Cite as

West African and Amerindian ancestry and risk of myocardial infarction and metabolic syndrome in the Central Valley population of Costa Rica

  • Edward A. Ruiz-Narváez
  • Lance Bare
  • Andre Arellano
  • Joseph Catanese
  • Hannia Campos
Original Investigation


Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n = 1,998) matched for age, sex, and area of residence, to estimate individual ancestry proportions. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using conditional (MI) and unconditional (MS and its components) logistic regression adjusting for relevant confounders. Mean individual ancestry proportions in cases and controls were 57.5 versus 57.8% for the Southern European, 38.4 versus 38.3% for the Amerindian and 4.1 versus 3.8% for the West African ancestry. Compared with Southern European ancestry, each 10% increase in West African ancestry was associated with a 29% increase in MI, OR (95% CI) = 1.29 (1.07, 1.56), and with a 30% increase on the risk of hypertension, OR (95% CI) = 1.30 (1.00, 1.70). Each 10% increase in Amerindian ancestry was associated with a 14% increase on the risk of MS, OR (95% CI) = 1.14 (1.00, 1.30), and 20% increase on the risk of impaired fasting glucose, OR (95% CI) = 1.20 (1.01, 1.42). These results show that the high variability of admixture proportions in the Central Valley population offers a unique opportunity to uncover the genetic basis of ethnic differences on the risk of disease.


  1. Agyemang C, Bhopal R (2003) Is the blood pressure of people from African origin adults in the UK higher or lower than that in European origin white people? A review of cross-sectional data. J Hum Hypertens 17:523–534CrossRefPubMedGoogle Scholar
  2. AHA (2009) American Heart Association: Heart Disease and Stroke Statistics-2009 Update. American Heart Association, DallasGoogle Scholar
  3. Bassuk SS, Manson JE (2005) Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol 99:1193–1204CrossRefPubMedGoogle Scholar
  4. Baylin A, Kabagambe EK, Siles X, Campos H (2002) Adipose tissue biomarkers of fatty acid intake. Am J Clin Nutr 76:750–757PubMedGoogle Scholar
  5. Baylin A, Kabagambe EK, Ascherio A, Spiegelman D, Campos H (2003) Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica. Circulation 107:1586–1591CrossRefPubMedGoogle Scholar
  6. Beynen AC, Katan MB (1985) Rapid sampling and long-term storage of subcutaneous adipose-tissue biopsies for determination of fatty acid composition. Am J Clin Nutr 42:317–322PubMedGoogle Scholar
  7. Campos H, Bailey SM, Gussak LS, Siles X, Ordovas JM, Schaefer EJ (1991) Relations of body habitus, fitness level, and cardiovascular risk factors including lipoproteins and apolipoproteins in a rural and urban Costa Rican population. Arterioscler Thromb 11:1077–1088PubMedGoogle Scholar
  8. Carvajal-Carmona LG, Ophoff R, Service S, Hartiala J, Molina J, Leon P, Ospina J, Bedoya G, Freimer N, Ruiz-Linares A (2003) Genetic demography of Antioquia (Colombia) and the Central Valley of Costa Rica. Hum Genet 112:534–541PubMedGoogle Scholar
  9. CDC (2008) National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention, AtlantaGoogle Scholar
  10. Chakraborty R, Weiss KM (1986) Frequencies of complex diseases in hybrid populations. Am J Phys Anthropol 70:489–503CrossRefPubMedGoogle Scholar
  11. Chakraborty R, Ferrell RE, Stern MP, Haffner SM, Hazuda HP, Rosenthal M (1986) Relationship of prevalence of non-insulin-dependent diabetes mellitus to Amerindian admixture in the Mexican Americans of San Antonio, Texas. Genet Epidemiol 3:435–454CrossRefPubMedGoogle Scholar
  12. Chaturvedi N (2003) Ethnic differences in cardiovascular disease. Heart 89:681–686CrossRefPubMedGoogle Scholar
  13. Clark LT, Ferdinand KC, Flack JM, Gavin JR 3rd, Hall WD, Kumanyika SK, Reed JW, Saunders E, Valantine HA, Watson K, Wenger NK, Wright JT (2001) Coronary heart disease in African Americans. Heart Dis 3:97–108CrossRefPubMedGoogle Scholar
  14. Douglas JG, Thibonnier M, Wright JT Jr (1996) Essential hypertension: racial/ethnic differences in pathophysiology. J Assoc Acad Minor Phys 7:16–21PubMedGoogle Scholar
  15. Escamilla MA (2001) Population isolates: their special value for locating genes for bipolar disorder. Bipolar Disord 3:299–317CrossRefPubMedGoogle Scholar
  16. Escamilla MA, Spesny M, Reus VI, Gallegos A, Meza L, Molina J, Sandkuijl LA, Fournier E, Leon PE, Smith LB, Freimer NB (1996) Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population. Am J Med Genet 67:244–253CrossRefPubMedGoogle Scholar
  17. Excoffier L, Smouse PE, Quattro JM (1992) Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data. Genetics 131:479–491PubMedGoogle Scholar
  18. Falkner B, Kushner H (1991) Interaction of sodium sensitivity and stress in young adults. Hypertension 17:I162–I165PubMedGoogle Scholar
  19. Gardner LI Jr, Stern MP, Haffner SM, Gaskill SP, Hazuda HP, Relethford JH, Eifler CW (1984) Prevalence of diabetes in Mexican Americans. Relationship to percent of gene pool derived from native American sources. Diabetes 33:86–92CrossRefPubMedGoogle Scholar
  20. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomilehto J, Zimmet P (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167CrossRefPubMedGoogle Scholar
  21. Germer S, Holland MJ, Higuchi R (2000) High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR. Genome Res 10:258–266CrossRefPubMedGoogle Scholar
  22. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, Wiedmeyer HM, Byrd-Holt DD (1998) Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 21:518–524CrossRefPubMedGoogle Scholar
  23. Hodge AM, Zimmet PZ (1994) The epidemiology of obesity. Baillieres Clin Endocrinol Metab 8:577–599CrossRefPubMedGoogle Scholar
  24. Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG, McKeigue PM (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72:1492–1504CrossRefPubMedGoogle Scholar
  25. Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004) Design and analysis of admixture mapping studies. Am J Hum Genet 74:965–978CrossRefPubMedGoogle Scholar
  26. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC (2001) Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 345:790–797CrossRefPubMedGoogle Scholar
  27. Hutchinson RG, Watson RL, Davis CE, Barnes R, Brown S, Romm F, Spencer JM, Tyroler HA, Wu K (1997) Racial differences in risk factors for atherosclerosis. The ARIC Study. Atherosclerosis Risk in Communities. Angiology 48:279–290CrossRefPubMedGoogle Scholar
  28. Kabagambe EK, Baylin A, Allan DA, Siles X, Spiegelman D, Campos H (2001) Application of the method of triads to evaluate the performance of food frequency questionnaires and biomarkers as indicators of long-term dietary intake. Am J Epidemiol 154:1126–1135CrossRefPubMedGoogle Scholar
  29. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefPubMedGoogle Scholar
  30. Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet 22:139–144CrossRefPubMedGoogle Scholar
  31. Lai CQ, Tucker KL, Choudhry S, Parnell LD, Mattei J, Garcia-Bailo B, Beckman K, Burchard EG, Ordovas JM (2009) Population admixture associated with disease prevalence in the Boston Puerto Rican health study. Hum Genet 125:199–209CrossRefPubMedGoogle Scholar
  32. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716CrossRefPubMedGoogle Scholar
  33. Lorenzo C, Serrano-Rios M, Martinez-Larrad MT, Gabriel R, Williams K, Gonzalez-Villalpando C, Stern MP, Hazuda HP, Haffner SM (2001) Was the historic contribution of Spain to the Mexican gene pool partially responsible for the higher prevalence of type 2 diabetes in mexican-origin populations? The Spanish Insulin Resistance Study Group, the San Antonio Heart Study, and the Mexico City Diabetes Study. Diabetes Care 24:2059–2064CrossRefPubMedGoogle Scholar
  34. Martinez-Marignac VL, Valladares A, Cameron E, Chan A, Perera A, Globus-Goldberg R, Wacher N, Kumate J, McKeigue P, O’Donnell D, Shriver MD, Cruz M, Parra EJ (2007) Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors. Hum Genet 120:807–819CrossRefPubMedGoogle Scholar
  35. McKeigue PM, Carpenter JR, Parra EJ, Shriver MD (2000) Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations. Ann Hum Genet 64:171–186CrossRefPubMedGoogle Scholar
  36. Melendez C (1982) Conquistadores y Pobladores: Orígenes Histórico-Sociales de los Costarricenses. Editorial Universidad Estatal a Distancia, San JoséGoogle Scholar
  37. Minor DS, Wofford MR, Jones DW (2008) Racial and ethnic differences in hypertension. Curr Atheroscler Rep 10:121–127CrossRefPubMedGoogle Scholar
  38. Morera B, Barrantes R (2004) Is the Central Valley of Costa Rica a genetic isolate? Rev Biol Trop 52:629–644PubMedGoogle Scholar
  39. Morera B, Barrantes R, Marin-Rojas R (2003) Gene admixture in the Costa Rican population. Ann Hum Genet 67:71–80CrossRefPubMedGoogle Scholar
  40. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB (2003) The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med 163:427–436CrossRefPubMedGoogle Scholar
  41. Pfaff CL, Barnholtz-Sloan J, Wagner JK, Long JC (2004) Information on ancestry from genetic markers. Genet Epidemiol 26:305–315CrossRefPubMedGoogle Scholar
  42. Primatesta P, Bost L, Poulter NR (2000) Blood pressure levels and hypertension status among ethnic groups in England. J Hum Hypertens 14:143–148CrossRefPubMedGoogle Scholar
  43. Pritchard JK, Przeworski M (2001) Linkage disequilibrium in humans: models and data. Am J Hum Genet 69:1–14CrossRefPubMedGoogle Scholar
  44. Reiner AP, Ziv E, Lind DL, Nievergelt CM, Schork NJ, Cummings SR, Phong A, Burchard EG, Harris TB, Psaty BM, Kwok PY (2005) Population structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study. Am J Hum Genet 76:463–477CrossRefPubMedGoogle Scholar
  45. Reiner AP, Carlson CS, Ziv E, Iribarren C, Jaquish CE, Nickerson DA (2007) Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study. Hum Genet 121:565–575CrossRefPubMedGoogle Scholar
  46. Ridker PM, Buring JE, Cook NR, Rifai N (2003) C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 107:391–397CrossRefPubMedGoogle Scholar
  47. Ruiz-Narvaez EA, Yang Y, Nakanishi Y, Kirchdorfer J, Campos H (2005) APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica. J Lipid Res 46:2605–2613CrossRefPubMedGoogle Scholar
  48. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH (2001) Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 344:3–10CrossRefPubMedGoogle Scholar
  49. Salmeron J, Hu FB, Manson JE, Stampfer MJ, Colditz GA, Rimm EB, Willett WC (2001) Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr 73:1019–1026PubMedGoogle Scholar
  50. Schneider S, Roessli D, Excoffier L (2000) Arlequin version 2.000. A software for population genetic data analysis. Genetics and Biometry Laboratory, Department of Anthropology. University of Geneva, SwitzerlandGoogle Scholar
  51. Service SK, Ophoff RA, Freimer NB (2001) The genome-wide distribution of background linkage disequilibrium in a population isolate. Hum Mol Genet 10:545–551CrossRefPubMedGoogle Scholar
  52. Shriver MD, Parra EJ, Dios S, Bonilla C, Norton H, Jovel C, Pfaff C, Jones C, Massac A, Cameron N, Baron A, Jackson T, Argyropoulos G, Jin L, Hoggart CJ, McKeigue PM, Kittles RA (2003) Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet 112:387–399PubMedGoogle Scholar
  53. Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O’Brien SJ, Reich D (2004) A high-density admixture map for disease gene discovery in African Americans. Am J Hum Genet 74:1001–1013CrossRefPubMedGoogle Scholar
  54. Svetkey LP, Simons-Morton D, Vollmer WM, Appel LJ, Conlin PR, Ryan DH, Ard J, Kennedy BM (1999) Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial. Arch Intern Med 159:285–293CrossRefPubMedGoogle Scholar
  55. Thiel BA (1977) Monografía de la Población de la República de Costa Rica en el siglo XIX. Editorial Costa Rica, San JoséGoogle Scholar
  56. Third Report of the National Cholesterol Education Program (NCEP) (2002) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106: 3143–421Google Scholar
  57. Wang S, Ray N, Rojas W, Parra MV, Bedoya G, Gallo C, Poletti G, Mazzotti G, Hill K, Hurtado AM, Camrena B, Nicolini H, Klitz W, Barrantes R, Molina JA, Freimer NB, Bortolini MC, Salzano FM, Petzl-Erler ML, Tsuneto LT, Dipierri JE, Alfaro EL, Bailliet G, Bianchi NO, Llop E, Rothhammer F, Excoffier L, Ruiz-Linares A (2008) Geographic patterns of genome admixture in Latin American Mestizos. PLoS Genet 4:e1000037CrossRefPubMedGoogle Scholar
  58. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS (1986) Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 8:II127–II134PubMedGoogle Scholar
  59. Zhu X, Luke A, Cooper RS, Quertermous T, Hanis C, Mosley T, Gu CC, Tang H, Rao DC, Risch N, Weder A (2005) Admixture mapping for hypertension loci with genome-scan markers. Nat Genet 37:177–181CrossRefPubMedGoogle Scholar
  60. Zoratti R, Godsland IF, Chaturvedi N, Crook D, Crook D, Stevenson JC, McKeigue PM (2000) Relation of plasma lipids to insulin resistance, nonesterified fatty acid levels, and body fat in men from three ethnic groups: relevance to variation in risk of diabetes and coronary disease. Metabolism 49:245–252CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Edward A. Ruiz-Narváez
    • 1
    • 2
  • Lance Bare
    • 3
  • Andre Arellano
    • 3
  • Joseph Catanese
    • 3
  • Hannia Campos
    • 4
  1. 1.Slone Epidemiology CenterBoston UniversityBostonUSA
  2. 2.Department of EpidemiologyBoston University School of Public HealthBostonUSA
  3. 3.CeleraAlamedaUSA
  4. 4.Department of Nutrition, Room 201Harvard School of Public HealthBostonUSA

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