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Genetic factors influencing bone mineral content in a black South African population

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Abstract

Bone mass differs according to ethnic classification, with individuals of African ancestry attaining the highest measurements across numerous skeletal sites. Elevated bone mass is even maintained in those individuals exposed to adverse environmental factors, suggesting a prominent genetic effect that may have clinical or therapeutic value. Using a candidate gene approach, we investigated associations of six candidate genes (ESR1, TNFRSF11A, TNFRSF11B, TNFSF11, SOST and SPP1) with bone mass at the hip and lumbar spine amongst pre-pubertal black South African children (mean age 10.6 years) who formed part of the longitudinal Birth to Twenty cohort. 151 black children were genotyped at 366 polymorphic loci, including 112 previously associated and 254 tagging single nucleotide polymorphisms (SNPs). Linear regression was used to highlight significant associations whilst adjusting for height, weight, sex and bone area. Twenty-seven markers (8 previously associated and 19 tag SNPs; P < 0.05) were found to be associated with either femoral neck (18) or lumbar spine (9) bone mineral content. These signals were derived from three genes, namely ESR1 (17), TNFRSF11B (9) and SPP1 (1). One marker (rs2485209) maintained its association with the femoral neck after correction for multiple testing (P = 0.038). When compared to results amongst Caucasian adults, we detected differences with respect to associated skeletal sites. Allele frequencies and linkage disequilibrium patterns were also significantly different between populations. Hence, our results support the existence of a strong genetic effect acting at the femoral neck in black South African children, whilst simultaneously highlighting possible causes that account for inter-ethnic bone mass diversity.

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Fig. 1

Notes

  1. Note that for the purposes of this study, ‘black’ is used to define individuals of African ancestry without known admixture, whilst ‘white’ denotes individuals of European descent.

References

  1. Han ZH, Palnitkar S, Rao DS, Nelson D, Parfitt AM (1996) Effect of ethnicity and age or menopause on the structure and geometry of iliac bone. J Bone Miner Res 11:1967–1975

    Article  PubMed  CAS  Google Scholar 

  2. Micklesfield LK, Norris SA, Pettifor JM (2011) Ethnicity and bone: a South African perspective. J Bone Miner Metab 29:257–267

    Article  PubMed  Google Scholar 

  3. Nelson DA, Pettifor JM, Norris S (2008) Chapter 26: Race, Ethnicity and Osteoporosis. In: Marcus R, Feldman D, Nelson DA, Rosen CJ (eds) Osteoporosis, vol I, 3rd edn. Elsevier Academic Press, London

    Google Scholar 

  4. Hill DD, Cauley JA, Sheu Y, Bunker CH, Patrick AL, Baker CE, Beckles GL, Wheeler VW, Zmuda JM (2008) Correlates of bone mineral density in men of African ancestry: the Tobago bone health study. Osteoporos Int 19:227–234

    Article  PubMed  CAS  Google Scholar 

  5. Melton LJ III, Marquez MA, Achenbach SJ, Tefferi A, O’Connor MK, O’Fallon WM, Riggs BL (2002) Variations in bone density among persons of African heritage. Osteoporos Int 13:551–559

    Article  Google Scholar 

  6. Vidulich L, Norris SA, Cameron N, Pettifor JM (2011) Bone mass and bone size in pre- or early pubertal 10-year-old black and white South African children and their parents. Calcif Tissue Int 88:281–293

    Article  PubMed  CAS  Google Scholar 

  7. Hui SL, Perkins AJ, Harezlak J, Peacock M, McClintock CL, Johnston CC Jr (2010) Velocities of bone mineral accrual in black and white American children. J Bone Miner Res 25:1527–1535

    Article  PubMed  Google Scholar 

  8. Li WF, Hou SX, Yu B, Li MM, Ferec C, Chen JM (2010) Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 127:249–285

    Article  PubMed  CAS  Google Scholar 

  9. Fausto-Sterling A (2008) The Bare Bones of Race. Soc Stud Sci 38:657–694

    Article  PubMed  Google Scholar 

  10. Thomas PA (2007) Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg 15(Suppl 1):S26–S30

    PubMed  Google Scholar 

  11. Ma J, Johns RA, Stafford RS (2007) Americans are not meeting current calcium recommendations. Am J Clin Nutr 85:1361–1366

    PubMed  CAS  Google Scholar 

  12. Jackson KA, Savaiano DA (2001) Lactose maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans. J Am Coll Nutr 20:198S–207S

    Article  PubMed  CAS  Google Scholar 

  13. MacKeown JM, Cleaton-Jones PE, Norris SA (2003) Nutrient intake among a longitudinal group of urban black South African children at four interceptions between 1995 and 2000. Nutrition Research 23:185–197

    Article  CAS  Google Scholar 

  14. Richter L, Norris S, Pettifor J, Yach D, Cameron N (2007) Cohort Profile: Mandela’s children: the 1990 Birth to Twenty study in South Africa. Int J Epidemiol 36:504–511

    Article  PubMed  Google Scholar 

  15. McVeigh JA, Norris SA, Cameron N, Pettifor JM (2004) Associations between physical activity and bone mass in black and white South African children at age 9 year. J Appl Physiol 97:1006–1012

    Article  PubMed  CAS  Google Scholar 

  16. Duren DL, Sherwood RJ, Choh AC, Czerwinski SA, Chumlea WC, Lee M, Sun SS, Demerath EW, Siervogel RM, Towne B (2007) Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study. Bone 40:464–470

    Article  PubMed  Google Scholar 

  17. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N (2008) A reference standard for the description of osteoporosis. Bone 42:467–475

    Article  PubMed  CAS  Google Scholar 

  18. Nanes MS, Kallen CB (2009) Clinical assessment of fracture risk and novel therapeutic strategies to combat osteoporosis. Fertil Steril 92:403–412

    Article  PubMed  CAS  Google Scholar 

  19. Tranah GJ, Taylor BC, Lui LY, Zmuda JM, Cauley JA, Ensrud KE, Hillier TA, Hochberg MC, Li J, Rhees BK, Erlich HA, Sternlicht MD, Peltz G, Cummings SR (2008) Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures. Calcif Tissue Int 83:155–166

    Article  PubMed  CAS  Google Scholar 

  20. Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K et al (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 151:528–537

    Article  PubMed  Google Scholar 

  21. Guthrie M (1948) The classification of the Bantu languages. Oxford University Press for the International African Institute, London

    Google Scholar 

  22. Lohman T, Roche A, Martorell R (1991) Anthropometric standardization reference manual. Human Kinetics, Champaign

    Google Scholar 

  23. Bianchi ML (2007) Osteoporosis in children and adolescents. Bone 41:486–495

    Article  PubMed  Google Scholar 

  24. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  25. de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D (2005) Efficiency and power in genetic association studies. Nat Genet 37:1217–1223

    Article  PubMed  Google Scholar 

  26. Smedley D, Haider S, Ballester B, Holland R, London D, Thorisson G, Kasprzyk A (2009) BioMart–biological queries made easy. BMC Genomics 10:22

    Article  PubMed  Google Scholar 

  27. Lin CH, Yeakley JM, McDaniel TK, Shen R (2009) Medium- to high-throughput SNP genotyping using VeraCode microbeads. In: Bugert P (ed) DNA and RNA profiling in human blood: methods and protocols, vol 496. Humana Press, New York

    Google Scholar 

  28. Gauderman WJ, Morrison JM (2006). QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydra.usc.edu/gxe/

  29. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575

    Article  PubMed  CAS  Google Scholar 

  30. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336–2337

    Article  PubMed  CAS  Google Scholar 

  31. Gennari L, Merlotti D, De Paola V, Calabro A, Becherini L, Martini G, Nuti R (2005) Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 161:307–320

    Article  PubMed  CAS  Google Scholar 

  32. Guggenbuhl P (2009) Osteoporosis in males and females: is there really a difference? Joint Bone Spine 76:595–601

    Article  PubMed  Google Scholar 

  33. Sand P, Luckhaus C, Schlurmann K, Gotz M, Deckert J (2002) Untangling the human estrogen receptor gene structure. J Neural Transm 109:567–583

    Article  PubMed  CAS  Google Scholar 

  34. Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    Article  PubMed  CAS  Google Scholar 

  35. Nguyen TV, Eisman JA (2006) Pharmacogenomics of osteoporosis: opportunities and challenges. J Musculoskelet Neuronal Interact 6:62–72

    PubMed  CAS  Google Scholar 

  36. Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K (2009) Osteoporosis: an age-related and gender-specific disease–a mini-review. Gerontology 55:3–12

    Article  PubMed  Google Scholar 

  37. Chantler S, Dickie K, Goedecke JH, Levitt NS, Lambert EV, Evans J, Joffe Y, Micklesfield LK (2011) Site-specific differences in bone mineral density in black and white premenopausal South African women. Osteoporos Int 23:533–542

    Article  PubMed  Google Scholar 

  38. Daniels ED, Pettifor JM, Schnitzler CM, Russell SW, Patel DN (1995) Ethnic differences in bone density in female South African nurses. J Bone Miner Res 10:359–367

    Article  PubMed  CAS  Google Scholar 

  39. Duren DL, Blangero J, Sherwood RJ, Seselj M, Dyer T, Cole SA, Lee M, Choh AC, Chumlea WC, Siervogel RM, Czerwinski SA, Towne B (2011) Cortical bone health shows significant linkage to chromosomes 2p, 3p, and 17q in 10-year-old children. Bone 49:1213–1218

    Article  PubMed  CAS  Google Scholar 

  40. Hasselstrom H, Karlsson KM, Hansen SE, Gronfeldt V, Froberg K, Andersen LB (2006) Sex differences in bone size and bone mineral density exist before puberty. The Copenhagen School Child Intervention Study (CoSCIS). Calcif Tissue Int 79:7–14

    Article  PubMed  CAS  Google Scholar 

  41. Poopedi MA, Norris SA, Pettifor JM (2010) Factors influencing the Vitamin D status of 10-year-old urban South African children. Public Health Nutrition 14:334–339

    Article  PubMed  Google Scholar 

  42. Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, Mahboubi S, Fan B, Frederick MM, Winer K, Shepherd JA (2007) The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab 92:2087–2099

    Article  PubMed  CAS  Google Scholar 

  43. Huang QY, Kung AW (2006) Genetics of osteoporosis. Mol Genet Metab 88:295–306

    Article  PubMed  CAS  Google Scholar 

  44. Karasik D, Dupuis J, Cho K, Cupples LA, Zhou Y, Kiel DP, Demissie S (2010) Refined QTLs of osteoporosis-related traits by linkage analysis with genome-wide SNPs: framingham SHARe. Bone 46:1114–1121

    Article  PubMed  CAS  Google Scholar 

  45. Gafni RI, Baron J (2007) Childhood bone mass acquisition and peak bone mass may not be important determinants of bone mass in late adulthood. Pediatrics 119(Suppl 2):S131–S136

    Article  PubMed  Google Scholar 

  46. Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA (2010) Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone 46:294–305

    Article  PubMed  Google Scholar 

  47. Uitterlinden AG, van Meurs JB, Rivadeneira F, Pols HA (2006) Identifying genetic risk factors for osteoporosis. J Musculoskelet Neuronal Interact 6:16–26

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Carnegie Cooperation Transformation Program and the National Research Foundation for their generous contributions toward funding for this study. Our gratitude is also extended to the Wellcome Trust, the South African Medical Research Council and, again, the National Research Foundation whose grants have supported the Birth to Twenty cohort and its smaller sub-cohort (the Bone Health study). Lastly, we’d like to thank the National Health Laboratory Service and the University of the Witwatersrand for supplying the necessary research equipment.

Conflict of interest

None.

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Author notes

  1. Zané Lombard

    Present address: Wits Bioinformatics, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa

Authors and Affiliations

  1. Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service, University of the Witwatersrand, Watkins-Pitchford Building, Room 109, Cnr Hospital and De Korte Street, Braamfontein, 2000, Johannesburg, South Africa

    Andrew May, Michèle Ramsay & Zané Lombard

  2. MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa

    John M. Pettifor & Shane A. Norris

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  1. Andrew May
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Correspondence to Michèle Ramsay.

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May, A., Pettifor, J.M., Norris, S.A. et al. Genetic factors influencing bone mineral content in a black South African population. J Bone Miner Metab 31, 708–716 (2013). https://doi.org/10.1007/s00774-013-0431-3

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  • DOI: https://doi.org/10.1007/s00774-013-0431-3

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