Searching for the human genetic factors standing in the way of universally effective vaccines

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 370, Issue 1671, 2015, Pages

  Mentzer, Alexander J ^a   O’Connor, Daniel ^b,c   Pollard, Andrew J ^b,c   Hill, Adrian V S ^a,b,c  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c NIHR OXFORD BIOMEDICAL RESEARCH CENTRE   (United Kingdom)

Author keywords

Gene; GWAS; Hepatitis B; Measles; Rubella; Vaccine

Indexed keywords

GENETIC VARIATION; HEPATITIS; HETEROGENEITY; MEASLES; PUBLIC HEALTH; RUBELLA; VACCINATION;

VACCINE;

ANTIBODY PRODUCTION; COMMUNICABLE DISEASE; GENETIC VARIATION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; IMMUNOLOGY;

ANTIBODY FORMATION; COMMUNICABLE DISEASES; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; VACCINES;

EID: 84929254067     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2014.0341     Document Type: Review

References (96)

1. Ada G. 2001 Vaccines and vaccination. N. Engl. J. Med. 345, 1042–1053. (doi:10.1056/NEJMra011223)
2. Nabel GJ. 2013 Designing tomorrow’s vaccines. N. Engl. J. Med. 368, 551–560. (doi:10.1056/NEJMra1204186)
3. Poland GA, Kennedy RB, Ovsyannikova IG. 2011 Vaccinomics and personalized vaccinology: is science leading us toward a new path of directed vaccine development and discovery? PLoS Pathog. 7, e1002344. (doi:10.1371/journal.ppat.1002344)
4. Heininger U, Bachtiar NS, Bahri P, Dana A, Dodoo A, Gidudu J, Santos E. 2012 The concept of vaccination failure. Vaccine 30, 1265–1268. (doi:10.1016/j.vaccine.2011.12.048)
5. Kimman TG, Vandebriel RJ, Hoebee B. 2007 Genetic variation in the response to vaccination. Commun. Genet. 10, 201–217. (doi:10.1159/000106559)
6. Siegrist CA, Aspinall R. 2009 B-cell responses to vaccination at the extremes of age. Nat. Rev. Immunol. 9, 185–194. (doi:10.1038/nri2508)
7. Klein SL, Marriott I, Fish EN. 2015 Sex-based differences in immune function and responses to vaccination. Trans. R. Soc. Trop. Med. Hyg. 109, 9–15. (doi:10.1093/trstmh/tru167)
8. Hsu LC et al. 1996 Ethnic differences in immune responses to hepatitis B vaccine. Am. J. Epidemiol. 143, 718–724. (doi:10.1093/oxfordjournals.aje.a008805)
9. Hohler T, Reuss E, Evers N, Dietrich E, Rittner C, Freitag CM, Vollmar J, Schneider PM, Fimmers R. 2002 Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins. Lancet 360, 991–995. (doi:10.1016/S0140-6736(02)11083-X)
10. Lemon SM, Thomas DL. 1997 Vaccines to prevent viral hepatitis. N. Engl. J. Med. 336, 196–204. (doi:10.1056/NEJM199701163360307)
11. Smolen KK, Gelinas L, Franzen L, Dobson S, Dawar M, Ogilvie G, Krajden M, Fortuno ES, Kollmann TR. 2012 Age of recipient and number of doses differentially impact human B and T cell immune memory responses to HPV vaccination. Vaccine 30, 3572–3579. (doi:10.1016/j.vaccine.2012.03.051)
12. Poland GA, Ovsyannikova IG, Jacobson RM. 2008 Vaccine immunogenetics: bedside to bench to population. Vaccine 26, 6183–6188. (doi:10.1016/j.vaccine.2008.06.057)
13. Hennig BJ et al. 2008 Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS ONE 3, e1898. (doi:10.1371/journal.pone.0001898)
14. Tan PL, Jacobson RM, Poland GA, Jacobsen SJ, Pankratz VS. 2001 Twin studies of immunogenicity: determining the genetic contribution to vaccine failure. Vaccine 19, 2434–2439. (doi:10.1016/S0264-410X(00)00468-0)
15. Jacobson RM, Poland GA. 2004 The genetic basis for measles vaccine failure. Acta Paediatr. 93, 43–46; discussion 46–47. (doi:10.1111/j.1651-2227.2004.tb03055.x)
16. Plotkin SA. 2010 Correlates of protection induced by vaccination. Clin. Vaccine Immunol. 17, 1055–1065. (doi:10.1128/CVI.00131-10)
17. Shim E, Galvani AP. 2012 Distinguishing vaccine efficacy and effectiveness. Vaccine 30, 6700–6705. (doi:10.1016/j.vaccine.2012.08.045)
18. Osterholm MT, Kelley NS, Sommer A, Belongia EA. 2012 Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet. Infect. Dis. 12, 36–44. (doi:10.1016/S1473-3099(11)70295-X)
19. Boraschi D et al. 2008 Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities. PLoS Negl. Trop. Dis. 2, e255. (doi:10.1371/journal.pntd.0000255)
20. Hill AV. 2006 Pre-erythrocytic malaria vaccines: towards greater efficacy. Nat. Rev. Immunol. 6, 21–32. (doi:10.1038/nri1746)
21. Lindemann M, Barsegian V, Siffert W, Ferencik S, Roggendorf M, Grosse-Wilde H. 2002 Role of G protein beta3 subunit C825 T and HLA class II polymorphisms in the immune response after HBV vaccination. Virology 297, 245–252. (doi:10.1006/viro.2002.1467)
22. Mineta M, Tanimura M, Tana T, Yssel H, Kashiwagi S, Sasazuki T. 1996 Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans. Int. Immunol. 8, 525–531. (doi:10.1093/intimm/8.4.525)
23. Yucesoy B et al. 2002 IL-1b gene polymorphisms influence hepatitis B vaccination. Vaccine 20, 3193–3196. (doi:10.1016/S0264-410X(02)00267-0)
24. McDermott AB, Zuckerman JN, Sabin CA, Marsh SG, Madrigal JA. 1997 Contribution of human leukocyte antigens to the antibody response to hepatitis B vaccination. Tissue Antigens 50, 8–14. (doi:10.1111/j.1399-0039.1997.tb02827.x)
25. Desombere I, Willems A, Leroux-Roels G. 1998 Response to hepatitis B vaccine: multiple HLA genes are involved. Tissue Antigens 51, 593–604. (doi:10.1111/j.1399-0039.1998.tb03001.x)
26. Hohler T et al. 1998 The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg. Hum. Immunol. 59, 212–218. (doi:10.1016/S0198-8859(98)00014-7)
27. De Silvestri A, Pasi A, Martinetti M, Belloni C, Tinelli C, Rondini G, Salvaneschi L, Cuccia M. 2001 Family study of non-responsiveness to hepatitis B vaccine confirms the importance of HLA class III C4A locus. Genes Immun. 2, 367–372. (doi:10.1038/sj.gene.6363792)
28. Hohler T, Stradmann-Bellinghausen B, Starke R, Sänger R, Victor A, Rittner C, Schneider PM. 2002 C4A deficiency and nonresponse to hepatitis B vaccination. J. Hepatol. 37, 387–392. (doi:10.1016/S0168-8278(02)00205-2)
29. Davila S et al. 2010 New genetic associations detected in a host response study to hepatitis B vaccine. Genes Immun. 11, 232–238. (doi:10.1038/gene.2010.1)
30. Png E, Thalamuthu A, Ong RTH, Snippe H, Boland GJ, Seielstad M. 2011 A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region. Hum. Mol. Genet. 20, 3893–3898. (doi:10.1093/hmg/ddr302)
31. Wu TW, Chu C-C, Ho T-Y, Chang Liao H-W, Lin S-K, Lin M, Lin HH, Wang L-Y. 2013 Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents. Hum. Genet. 132, 1131–1139. (doi:10.1007/s00439-013-1320-5)
32. Pan L et al. 2014 A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations. Hum. Mol. Genet. 23, 2210–2219. (doi:10.1093/hmg/ddt586)
33. Haralambieva IH, Dhiman N, Ovsyannikova IG, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA. 2010 20-50-Oligoadenylate synthetase singlenucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine. Hum. Immunol. 71, 383–391. (doi:10.1016/j.humimm.2010.01.004)
34. Haralambieva IH, Lambert ND, Ovsyannikova IG, Kennedy RB, Larrabee BR, Pankratz VS, Poland GA. 2014 Associations between single nucleotide polymorphisms in cellular viral receptors and attachment factor-related genes and humoral immunity to rubella vaccination. PLoS ONE 9, e99997. (doi:10.1371/journal.pone.0099997)
35. Ovsyannikova IG, Dhiman N, Haralambieva IH, Vierkant RA, O’Byrne MM, Jacobson RM, Poland GA. 2010 Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. Hum. Genet. 127, 207–221. (doi:10.1007/s00439-009-0763-1)
36. Ovsyannikova IG, Pankratz VS, Larrabee BR, Jacobson RM, Poland GA. 2014 HLA genotypes and rubella vaccine immune response: additional evidence. Vaccine 32, 4206–4213. (doi:10.1016/j.vaccine.2014.04.091)
37. Ovsyannikova IG, Jacobson RM, Vierkant RA, O’Byrne MM, Poland GA. 2009 Replication of rubella vaccine population genetic studies: validation of HLA genotype and humoral response associations. Vaccine 27, 6926–6931. (doi:10.1016/j.vaccine.2009.08.109)
38. Lambert ND, Haralambieva IH, Kennedy RB, Ovsyannikova IG, Pankratz VS, Poland GA. 2014 Polymorphisms in HLA-DPB1 Are associated with differences in rubella virus-specific humoral immunity after vaccination. J. Infect. Dis. 211, 898–905. (doi:10.1093/infdis/jiu553)
39. Dhiman N, Poland GA, Cunningham JM, Jacobson RM, Ovsyannikova IG, Vierkant RA, Wu Y, Pankratz VS. 2007 Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors. J. Allergy Clin. Immunol. 120, 666–672. (doi:10.1016/j.jaci.2007.04.036)
40. Dhiman N, Ovsyannikova IG, Vierkant RA, Ryan JE, Pankratz VS, Jacobson RM, Poland GA. 2008 Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine 26, 1731–1736. (doi:10.1016/j.vaccine.2008.01.017)
41. Haralambieva IH, Ovsyannikova IG, Kennedy RB, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA. 2011 Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination. Vaccine 29, 7883–7895. (doi:10.1016/j.vaccine.2011.08.083)
42. Haralambieva IH, Umlauf BJ, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA. 2011 Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine. Vaccine 29, 8988–8997. (doi:10.1016/j.vaccine.2011.09.043)
43. Ovsyannikova IG, Haralambieva IH, Vierkant RA, O’Byrne MM, Jacobson RM, Poland GA. 2011 The association of CD46, SLAM and CD209 cellular receptor gene SNPs with variations in measles vaccine-induced immune responses: a replication study and examination of novel polymorphisms. Hum. Hered. 72, 206–223. (doi:10.1159/000331585)
44. Ovsyannikova IG, Haralambieva IH, Vierkant RA, O’Byrne MM, Jacobson RM, Poland GA. 2012 Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine. Pharmacogenet. Genomics 22, 20–31. (doi:10.1097/FPC.0b013e32834df186)
45. Ovsyannikova IG, Haralambieva IH, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA. 2011 The role of polymorphisms in Toll-like receptors and their associated intracellular signaling genes in measles vaccine immunity. Hum. Genet. 130, 547–561. (doi:10.1007/s00439-011-0977-x)
46. Ovsyannikova IG, Pankratz VS, Vierkant RA, Jacobson RM, Poland GA. 2012 Consistency of HLA associations between two independent measles vaccine cohorts: a replication study. Vaccine 30, 2146–2152. (doi:10.1016/j.vaccine.2012.01.038)
47. Jacobson RM, Ovsyannikova IG, Vierkant RA, Pankratz VS, Poland GA. 2011 Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measlescontaining vaccine: persistence, dampening, and extinction of associations found after a first dose. Vaccine 29, 7982–7991. (doi:10.1016/j.vaccine.2011.08.060)
48. Ovsyannikova IG, Pankratz VS, Vierkant RA, Jacobson RM, Poland GA. 2006 Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine. J. Infect. Dis. 193, 655–663. (doi:10.1086/500144)
49. Hennig BJ, Hall AJ. 2012 Host genetic factors in hepatitis B infection, liver cancer and vaccination response: a review with a focus on Africa. Sci. Tot. Environ. 423, 202–209. (doi:10.1016/j.scitotenv.2010.09.036)
50. O’Connor D, Pollard AJ. 2013 Characterizing vaccine responses using host genomic and transcriptomic analysis. Clin. Infect. Dis. 57, 860–869. (doi:10.1093/cid/cit373)
51. Poland GA, Ovsyannikova IG, Jacobson RM. 2008 Personalized vaccines: the emerging field of vaccinomics. Expert Opin. Biol. Ther. 8, 1659–1667. (doi:10.1517/14712598.8.11.1659)
52. Caillat-Zucman S et al. 1998 Distinct HLA class II alleles determine antibody response to vaccination with hepatitis B surface antigen. Kidney Int. 53, 1626–1630. (doi:10.1046/j.1523-1755.1998.00909.x)
53. Hohler T, Reuss E, Freitag CM, Schneider PM. 2005 A functional polymorphism in the IL-10 promoter influences the response after vaccination with HBsAg and hepatitis A. Hepatology 42, 72–76. (doi:10.1002/hep.20740)
54. Milich DR, Leroux-Roels GG. 2003 Immunogenetics of the response to HBsAg vaccination. Autoimmun. Rev. 2, 248–257. (doi:10.1016/S1568-9972(03)00031-4)
55. Lee SH, Wray NR. 2013 Novel genetic analysis for case-control genome-wide association studies: quantification of power and genomic prediction accuracy. PLoS ONE 8, e71494. (doi:10.1371/journal.pone.0071494)
56. Li D, Lewinger JP, Gauderman WJ, Murcray CE, Conti D. 2011 Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies. Genet. Epidemiol. 35, 790–799. (doi:10.1002/gepi.20628)
57. van der Sluis S, Posthuma D, Nivard MG, Verhage M, Dolan CV. 2013 Power in GWAS: lifting the curse of the clinical cut-off. Mol. Psychiatry 18, 2–3. (doi:10.1038/mp.2012.65)
58. Wood AR et al. 2014 Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46, 1173–1186. (doi:10.1038/ng.3097)
59. Teslovich TM et al. 2010 Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713. (doi:10.1038/nature09270)
60. Clifford HD, Hayden CM, Khoo S-K, Naniche D, Mandomando IM, Zhang G, Richmond P, Le Souëf PN. 2012 Polymorphisms in key innate immune genes and their effects on measles vaccine responses and vaccine failure in children from Mozambique. Vaccine 30, 6180–6185. (doi:10.1016/j.vaccine.2012.07.063)
61. Ladhani SN, Davila S, Hibberd ML, Heath PT, Ramsay ME, Slack MPE, Pollard AJ, Booy R. 2010 Association between single-nucleotide polymorphisms in Mal/TIRAP and interleukin-10 genes and susceptibility to invasive haemophilus influenzae serotype b infection in immunized children. Clin. Infect. Dis. 51, 761–767. (doi:10.1086/656236)
62. Chapman SJ, Hill AV. 2012 Human genetic susceptibility to infectious disease. Nat. Rev. Genet. 13, 175–188. (doi:10.1038/nrg3114)
63. Hill AV. 2012 Evolution, revolution and heresy in the genetics of infectious disease susceptibility. Phil. Trans. R. Soc. B 367, 840–849. (doi:10.1098/rstb.2011.0275)
64. Teo YY, Fry AE, Bhattacharya K, Small KS, Kwiatkowski DP, Clark TG. 2009 Genome-wide comparisons of variation in linkage disequilibrium. Genome Res. 19, 1849–1860. (doi:10.1101/gr.092189.109)
65. Marchini J, Howie B, Myers S, McVean G, Donnelly P. 2007 A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913. (doi:10.1038/ng2088)
66. van den Hof S, Wallinga J, Widdowson MA, Conyn-van Spaendonck MA. 2002 Protecting the vaccinating population in the face of a measles epidemic: assessing the impact of adjusted vaccination schedules. Epidemiol. Infect. 128, 47–57. (doi:10.1017/S0950268801006409)
67. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist C-A. 1999 Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet 354, 2063–2068. (doi:10.1016/S0140-6736(99)04377-9)
68. Szmuness W et al. 1982 Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection. N. Engl. J. Med.307, 1481–1486. (doi:10.1056/NEJM198212093072403)
69. Watanabe H, Okumura M, Hirayama K, Sasazuki T. 1990 HLA-Bw54-DR4-DRw53-DQw4 haplotype controls nonresponsiveness to hepatitis-B surface antigen via CD8-positive suppressor T cells. Tissue Antigens 36, 69–74. (doi:10.1111/j.1399-0039.1990.tb01802.x)
70. Yang J, Lee SH, Goddard ME, Visscher PM. 2011 GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82. (doi:10.1016/j.ajhg.2010.11.011)
71. Zhou X, Stephens M. 2012 Genome-wide efficient mixed-model analysis for association studies. Nat. Genet. 44, 821–824. (doi:10.1038/ng.2310)
72. Jallow M et al. 2009 Genome-wide and fineresolution association analysis of malaria in West Africa. Nat. Genet. 41, 657–665. (doi:10.1038/ng.388)
73. Desombere I, Cao T, Gijbels Y, Leroux-Roels G. 2005 Non-responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation. Clin. Exp. Immunol. 140, 126–137. (doi:10.1111/j.1365-2249.2004.02749.x)
74. Kruger A, Adams P, Hammer J, Bocher WO, Schneider PM, Rittner C, Hoehler T. 2005 Hepatitis B surface antigen presentation and HLA-DRB1*—lessons from twins and peptide binding studies. Clin. Exp. Immunol. 140, 325–332. (doi:10.1111/j.1365-2249.2005.02765.x)
75. Salazar M et al. 1995 Normal HBsAg presentation and T-cell defect in the immune response of nonresponders. Immunogenetics 41, 366–374. (doi:10.1007/BF00163994)
76. Kamatani Y et al. 2009 A genome-wide association study identifies variants in the HLADP locus associated with chronic hepatitis B in Asians. Nat. Genet. 41, 591–595. (doi:10.1038/ng.348)
77. Carroll MC. 1998 The role of complement and complement receptors in induction and regulation of immunity. Annu. Rev. Immunol. 16, 545–568. (doi:10.1146/annurev.immunol.16.1.545)
78. Haralambieva IH, Ovsyannikova IG, Pankratz VS, Kennedy RB, Jacobson RM, Poland GA. 2013 The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches. Expert Rev. Vaccines 12, 57–70. (doi:10.1586/erv.12.134)
79. Jacobson RM, Ovsyannikova IG, Poland GA. 2009 Genetic basis for variation of vaccine response: our studies with rubella vaccine. Paediatr. Child Health 19, S156–S159. (doi:10.1016/j.paed.2009.08.019)
80. Newport MJ, Goetghebuer T, Weiss HA, Whittle H, Siegrist C-A, Marchant A. 2004 Genetic regulation of immune responses to vaccines in early life. Genes Immun. 5, 122–129. (doi:10.1038/sj.gene.6364051)
81. Li S et al. 2014 Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat. Immunol. 15, 195–204. (doi:10.1038/ni.2789)
82. Fairfax BP et al. 2014 Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science 343, 1246949. (doi:10.1126/science.1246949)
83. Fairfax BP, Knight JC. 2014 Genetics of gene expression in immunity to infection. Curr. Opin. Immunol. 30, 63–71. (doi:10.1016/j.coi.2014.07.001)
84. Kibler KV et al. 2011 Improved NYVAC-based vaccine vectors. PLoS ONE 6, e25674. (doi:10.1371/journal.pone.0025674)
85. McLachlan JB et al. 2008 Mast cell activators: a new class of highly effective vaccine adjuvants. Nat. Med. 14, 536–541. (doi:10.1038/nm1757)
86. Feenstra B et al. 2014 Common variants associated with general and MMR vaccine-related febrile seizures. Nat. Genet. 46, 1274–1282. (doi:10.1038/ng.3129)
87. Reif DM, McKinney BA, Motsinger AA, Chanock SJ, Edwards KM, Rock MT, Moore JH, Crowe JE. 2008 Genetic basis for adverse events after smallpox vaccination. J. Infect. Dis. 198, 16–22. (doi:10.1086/588670)
88. Cherry JD. 2012 Epidemic pertussis in 2012–the resurgence of a vaccine-preventable disease. N. Engl. J. Med. 367, 785–787. (doi:10.1056/NEJMp1209051)
89. Barton LL. 2002 Immunology series: vaccines. N. Engl. J. Med. 346, 864–866. (doi:10.1056/NEJM200203143461118)
90. Poland GA et al. 1997 Measles reimmunization in children seronegative after initial immunization. JAMA 277, 1156–1158. (doi:10.1001/jama.1997.03540380070034)
91. Kong A et al. 2009 Parental origin of sequence variants associated with complex diseases. Nature 462, 868–874. (doi:10.1038/nature08625)
92. Casanova JL, Abel L. 2007 Primary immunodeficiencies: a field in its infancy. Science 317, 617–619. (doi:10.1126/science.1142963)
93. Grossman SR et al. 2013 Identifying recent adaptations in large-scale genomic data. Cell 152, 703–713. (doi:10.1016/j.cell.2013.01.035)
94. Gurdasani D et al. 2014 The African Genome Variation Project shapes medical genetics in Africa. Nature 517, 327–332. (doi:10.1038/nature13997)
95. Karlsson EK et al. 2013 Natural selection in a Bangladeshi population from the cholera-endemic Ganges river delta. Sci. Transl. Med. 5, 192ra186. (doi:10.1126/scitranslmed.3006338)
96. Karlsson EK, Kwiatkowski DP, Sabeti PC. 2014 Natural selection and infectious disease in human populations. Nat. Rev. Genet. 15, 379–393. (doi:10.1038/nrg3734)