Pediatric Nephrology

, Volume 25, Issue 11, pp 2257–2268 | Cite as

Genetic studies of IgA nephropathy: past, present, and future

  • Krzysztof Kiryluk
  • Bruce A. Julian
  • Robert J. Wyatt
  • Francesco Scolari
  • Hong Zhang
  • Jan Novak
  • Ali G. Gharavi
Educational Review


Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN.


IgA nephropathy Genetics Hereditary disease IgA1 glycosylation Genome-wide association study 



Krzysztof Kiryluk is supported by the Daland Fellowship from the American Philosophical Society and Grant Number KL2 RR024157 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Bruce A. Julian, Robert J. Wyatt, Francesco Scolari, Jan Novak, and Ali G. Gharavi are supported by Grant Number DK082753 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The authors also acknowledge other grants from NIDDK supporting their research of IgAN: DK078244, DK080301, DK075868, DK071802, and DK077279. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR, NIDDK, or NIH.

Conflicts of Interest


Supplementary material

467_2010_1500_MOESM1_ESM.doc (3.6 mb)
Table 1S Index of published genetic association studies in IgA nephropathy sorted by publication year (data from 1994 to 09/01/2009) (DOC 3642 kb)


  1. 1.
    Beerman I, Novak J, Wyatt RJ, Julian BA, Gharavi AG (2007) The genetics of IgA nephropathy. Nat Clin Pract Nephrol 3:325–338CrossRefPubMedGoogle Scholar
  2. 2.
    D’Amico G (1987) The commonest glomerulonephritis in the world; IgA nephropathy. Q J Med 64:709–727Google Scholar
  3. 3.
    Donadio JV, Grande JP (2002) IgA nephropathy. N Engl J Med 347:738–748CrossRefPubMedGoogle Scholar
  4. 4.
    Barratt J, Feehally J (2005) IgA nephropathy. J Am Soc Nephrol 16:2088–2097CrossRefPubMedGoogle Scholar
  5. 5.
    D’Amico G, Imbasciati E, Barbiano Di Belgioioso G, Bertoli S, Fogazzi G, Ferrario F, Fellin G, Ragni A, Colasanti G, Minetti L, Ponticelli C (1985) Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients. Medicine 64:49–60PubMedGoogle Scholar
  6. 6.
    Hall YN, Fuentes EF, Chertow GM, Olson JL (2004) Race/ethnicity and disease severity in IgA nephropathy. BMC Nephrol 5:10CrossRefPubMedGoogle Scholar
  7. 7.
    Hoy WE, Hughson MD, Smith SM, Megill DM (1993) Mesangial proliferative glomerulonephritis in southwestern American Indians. Am J Kidney Dis 21:486–496PubMedGoogle Scholar
  8. 8.
    Smith SM, Harford AM (1995) IgA nephropathy in renal allografts: increased frequency in Native American patients. Ren Fail 17:449–456CrossRefPubMedGoogle Scholar
  9. 9.
    Hughson MD, Megill DM, Smith SM, Tung KS, Miller G, Hoy WE (1989) Mesangiopathic glomerulonephritis in Zuni (New Mexico) Indians. Arch Pathol Lab Med 113:148–157PubMedGoogle Scholar
  10. 10.
    O’Connell PJ, Ibels LS, Thomas MA, Harris M, Eckstein RP (1987) Familial IgA nephropathy: a study of renal disease in an Australian aboriginal family. Aust NZ J Med 17:27–33Google Scholar
  11. 11.
    Casiro OG, Stanwick RS, Walker RD (1988) The prevalence of IgA nephropathy in Manitoba Native Indian children. Can J Public Health 79:308–310PubMedGoogle Scholar
  12. 12.
    Julian BA, Quiggins PA, Thompson JS, Woodford SY, Gleason K, Wyatt RJ (1985) Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N Engl J Med 312:202–208CrossRefPubMedGoogle Scholar
  13. 13.
    Levy M (1989) Familial cases of Berger’s disease and anaphylactoid purpura more frequent than previously thought. Am J Med 87:246–248CrossRefPubMedGoogle Scholar
  14. 14.
    Paterson AD, Liu XQ, Wang K, Magistroni R, Song X, Kappel J, Klassen J, Cattran D, St George-Hyslop P, Pei Y (2007) Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36. J Am Soc Nephrol 18:2408–2415CrossRefPubMedGoogle Scholar
  15. 15.
    Scolari F, Amoroso A, Savoldi S, Mazzola G, Prati E, Valzorio B, Viola BF, Nicola B, Movilli E, Sandrini M, Campanini M, Maiorca R (1999) Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis 33:857–865CrossRefPubMedGoogle Scholar
  16. 16.
    Karnib HH, Sanna-Cherchi S, Zalloua PA, Medawar W, D’Agati VD, Lifton RP, Badr K, Gharavi AG (2007) Characterization of a large Lebanese family segregating IgA nephropathy. Nephrol Dial Transplant 22:772–777CrossRefPubMedGoogle Scholar
  17. 17.
    Johnston PA, Brown JS, Braumholtz DA, Davison AM (1992) Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry. Q J Med 84:619–627PubMedGoogle Scholar
  18. 18.
    Rambausek M, Hartz G, Waldherr R, Andrassy K, Ritz E (1987) Familial glomerulonephritis. Pediatr Nephrol 1:416–418CrossRefPubMedGoogle Scholar
  19. 19.
    Schena FP, Scivittaro V, Ranieri E, Sinico R, Benuzzi S, Di Cillo M, Aventaggiato L (1993) Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy. Clin Exp Immunol 92:139–144CrossRefPubMedGoogle Scholar
  20. 20.
    Schena FP, Scivittaro V, Ranieri E (1993) IgA nephropathy: pros and cons for a familial disease. Contrib Nephrol 104:36–45PubMedGoogle Scholar
  21. 21.
    Frasca GM, Soverini L, Gharavi AG, Lifton RP, Canova C, Preda P, Vangelista A, Stefoni S (2004) Thin basement membrane disease in patients with familial IgA nephropathy. J Nephrol 17:778–785PubMedGoogle Scholar
  22. 22.
    Durner M, Greenberg DA, Hodge SE (1992) (1992) Inter- and intrafamilial heterogeneity: effective sampling strategies and comparison of analysis methods. Am J Hum Genet 51:859–870PubMedGoogle Scholar
  23. 23.
    Durner M, Greenberg DA (1992) Effect of heterogeneity and assumed mode of inheritance on lod scores. Am J Med Genet 42:271–275CrossRefPubMedGoogle Scholar
  24. 24.
    Cavalli-Sforza LL, King MC (1986) Detecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data. Am J Hum Genet 38:599–616PubMedGoogle Scholar
  25. 25.
    Ott J (1986) The number of families required to detect or exclude linkage heterogeneity. Am J Hum Genet 39:159–165PubMedGoogle Scholar
  26. 26.
    Gharavi AG, Yan Y, Scolari F, Schena FP, Frasca GM, Ghiggeri GM, Cooper K, Amoroso A, Viola BF, Battini G, Caridi G, Canova C, Farhi A, Subramanian V, Nelson-Williams C, Woodford S, Julian BA, Wyatt RJ, Lifton RP (2000) IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet 26:354–357CrossRefPubMedGoogle Scholar
  27. 27.
    Bisceglia L, Cerullo G, Forabosco P, Torres DD, Scolari F, Di Perna M, Foramitti M, Amoroso A, Bertok S, Floege J, Mertens PR, Zerres K, Alexopoulos E, Kirmizis D, Ermelinda M, Zelante L, Schena FP, European IgAN Consortium (2006) Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Hum Genet 79:1130–1134CrossRefPubMedGoogle Scholar
  28. 28.
    Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306–309CrossRefPubMedGoogle Scholar
  29. 29.
    Obara W, Iida A, Suzuki Y, Tanaka T, Akiyama F, Maeda S, Ohnishi Y, Yamada R, Tsunoda T, Takei T, Ito K, Honda K, Uchida K, Tsuchiya K, Yumura W, Ujiie T, Nagane Y, Nitta K, Miyano S, Narita I, Gejyo F, Nihei H, Fujioka T, Nakamura Y (2003) Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients. J Hum Genet 48:293–299PubMedGoogle Scholar
  30. 30.
    Ohtsubo S, Iida A, Nitta K, Tanaka T, Yamada R, Ohnishi Y, Maeda S, Tsunoda T, Takei T, Obara W, Akiyama F, Ito K, Honda K, Uchida K, Tsuchiya K, Yumura W, Ujiie T, Nagane Y, Miyano S, Suzuki Y, Narita I, Gejyo F, Fujioka T, Nihei H, Nakamura Y (2005) Association of a single-nucleotide polymorphism in the immunoglobulin mu-binding protein 2 gene with immunoglobulin A nephropathy. J Hum Genet 50:30–35CrossRefPubMedGoogle Scholar
  31. 31.
    (1999) Freely associating. Nat Genet 22:1–2Google Scholar
  32. 32.
    von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457CrossRefGoogle Scholar
  33. 33.
    Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE, Zou GY, Hutchings K, Johnson CY, Tait V, Wiens M, Golding J, van Duijn C, McLaughlin J, Paterson A, Wells G, Fortier I, Freedman M, Zecevic M, King R, Infante-Rivard C, Stewart A, Birkett N (2009) STrengthening the REporting of Genetic Association Studies (STREGA)-an extension of the STROBE statement. Genet Epidemiol 33:581–598CrossRefPubMedGoogle Scholar
  34. 34.
    Hiki Y, Odani H, Takahashi M, Yasuda Y, Nishimoto A, Iwase H, Shinzato T, Kobayashi Y, Maeda K (2001) Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy. Kidney Int 59:1077–1085CrossRefPubMedGoogle Scholar
  35. 35.
    Tomana M, Matousovic K, Julian BA, Radl J, Konecny K, Mestecky J (1997) Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int 52:509–516CrossRefPubMedGoogle Scholar
  36. 36.
    Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999) Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest 104:73–81CrossRefPubMedGoogle Scholar
  37. 37.
    Raska M, Moldoveanu Z, Suzuki H, Brown R, Kulhavy R, Hall S, Vu HL, Carlsson F, Lindahl G, Tomana M, Julian BA, Wyatt RJ, Mestecky J, Novak J (2007) Identification and characterization of CMP-NeuAc:GalNAc-IgA1 α2, 6-sialyltransferase in IgA1-producing cells. J Mol Biol 369:69–78CrossRefPubMedGoogle Scholar
  38. 38.
    Suzuki H, Moldoveanu Z, Hall S, Brown R, Vu HL, Novak L, Julian BA, Tomana M, Wyatt RJ, Edberg JE, Alarcón GS, Kimberly RP, Tomino Y, Mestecky J, Novak J (2008) IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest 118:629–639PubMedGoogle Scholar
  39. 39.
    Li GS, Zhang H, Lv JC, Shen Y, Wang HY (2007) Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney Int 71:448–453CrossRefPubMedGoogle Scholar
  40. 40.
    Zhu L, Tang W, Li G, Lv J, Ding J, Yu L, Zhao M, Li Y, Zhang X, Shen Y, Zhang H, Wang H (2009) Interaction between variants of two glycosyltransferase genes in IgA nephropathy. Kidney Int 76:190–198CrossRefPubMedGoogle Scholar
  41. 41.
    Pirulli D, Crovella S, Ulivi S, Zadro C, Bertok S, Rendine S, Scolari F, Foramitti M, Ravani P, Roccatello D, Savoldi S, Cerullo G, Lanzilotta SG, Bisceglia L, Zelante L, Floege J, Alexopoulos E, Kirmizis D, Ghiggeri GM, Frasca G, Schena FP, Amoroso A (2009) Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy. J Nephrol 22:152–159PubMedGoogle Scholar
  42. 42.
    Suzuki H, Moldoveanu Z, Hall S, Brown R, Vu HL, Novak L, Julian BA, Tomana M, Wyatt RJ, Edberg JC, Alarcon GS, Kimberly RP, Tomino Y, Mestecky J, Novak J (2008) IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest 118:629–639PubMedGoogle Scholar
  43. 43.
    Buck KS, Smith AC, Molyneux K, El-Barbary H, Feehally J, Barratt J (2008) B-cell O-galactosyltransferase activity, and expression of O-glycosylation genes in bone marrow in IgA nephropathy. Kidney Int 73:1128–1136CrossRefPubMedGoogle Scholar
  44. 44.
    Smith AC, de Wolff JF, Molyneux K, Feehally J, Barratt J (2006) O-glycosylation of serum IgD in IgA nephropathy. J Am Soc Nephrol 17:1192–1199CrossRefPubMedGoogle Scholar
  45. 45.
    Moldoveanu Z, Wyatt RJ, Lee JY, Tomana M, Julian BA, Mestecky J, Huang WQ, Anreddy SR, Hall S, Hastings MC, Lau KK, Cook WJ, Novak J (2007) Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 71:1148–1154CrossRefPubMedGoogle Scholar
  46. 46.
    Lau KK, Wyatt RJ, Moldoveanu Z, Tomana M, Julian BA, Hogg RJ, Lee JY, Huang WQ, Mestecky J, Novak J (2007) Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schonlein purpura. Pediatr Nephrol 22:2067–2072CrossRefPubMedGoogle Scholar
  47. 47.
    Gharavi AG, Moldoveanu Z, Wyatt RJ, Barker CV, Woodford SY, Lifton RP, Mestecky J, Novak J, Julian BA (2008) Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy. J Am Soc Nephrol 19:1008–1014CrossRefPubMedGoogle Scholar
  48. 48.
    Lin X, Ding J, Zhu L, Shi S, Jiang L, Zhao M, Zhang H (2009) Aberrant galactosylation of IgA1 is involved in the genetic susceptibility of Chinese patients with IgA nephropathy. Nephrol Dial Transplant 24:3372–3375CrossRefPubMedGoogle Scholar
  49. 49.
    Tam KY, Leung JC, Chan LY, Lam MF, Tang SC, Lai KN (2009) Macromolecular IgA1 taken from patients with familial IgA nephropathy or their asymptomatic relatives have higher reactivity to mesangial cells in vitro. Kidney Int 75:1330–1339CrossRefPubMedGoogle Scholar
  50. 50.
    Kiryluk K, Moldoveanu Z, Sanders JT, Suzuki H, Julian BA, Mesteky J, Novak J, Gharavi AG, Wyatt RJ (2009) Aberrant glycosylation of IgA1 is inherited in pediatric Henoch-Schönlein nephritis. J Am Soc Nephrol 20:435A (abstract PO1408)Google Scholar
  51. 51.
    Suzuki H, Fan R, Zhang Z, Brown R, Hall S, Julian BA, Chatham WW, Suzuki Y, Wyatt RJ, Moldoveanu Z, Lee JY, Robinson J, Tomana M, Tomino Y, Mestecky J, Novak J (2009) Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119:1668–1677PubMedGoogle Scholar
  52. 52.
    Weidinger S, Gieger C, Rodriguez E, Baurecht H, Mempel M, Klopp N, Gohlke H, Wagenpfeil S, Ollert M, Ring J, Behrendt H, Heinrich J, Novak N, Bieber T, Kramer U, Berdel D, von Berg A, Bauer CP, Herbarth O, Koletzko S, Prokisch H, Mehta D, Meitinger T, Depner M, von Mutius E, Liang L, Moffatt M, Cookson W, Kabesch M, Wichmann HE, Illig T (2008) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 4:e1000166CrossRefPubMedGoogle Scholar
  53. 53.
    Denham S, Koppelman GH, Blakey J, Wjst M, Ferreira MA, Hall IP, Sayers I (2008) Meta-analysis of genome-wide linkage studies of asthma and related traits. Respir Res 9:38CrossRefPubMedGoogle Scholar
  54. 54.
    Hardy J, Singleton A (2009) Genomewide association studies and human disease. N Engl J Med 360:1759–1768CrossRefPubMedGoogle Scholar
  55. 55.
    Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909CrossRefPubMedGoogle Scholar
  56. 56.
    Dudbridge F, Gusnanto A (2008) Estimation of significance thresholds for genomewide association scans. Genet Epidemiol 32:227–234CrossRefPubMedGoogle Scholar
  57. 57.
    Hirschhorn JN, Daly MJ (2005) Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 6:95–108CrossRefPubMedGoogle Scholar
  58. 58.
    Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923CrossRefPubMedGoogle Scholar
  59. 59.
    Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308:385–389CrossRefPubMedGoogle Scholar
  60. 60.
    Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447:661–678CrossRefGoogle Scholar
  61. 61.
    Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463CrossRefPubMedGoogle Scholar
  62. 62.
    van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhernakova A, Inouye M, Wapenaar MC, Barnardo MC, Bethel G, Holmes GK, Feighery C, Jewell D, Kelleher D, Kumar P, Travis S, Walters JR, Sanders DS, Howdle P, Swift J, Playford RJ, McLaren WM, Mearin ML, Mulder CJ, McManus R, McGinnis R, Cardon LR, Deloukas P, Wijmenga C (2007) A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 39:827–829CrossRefPubMedGoogle Scholar
  63. 63.
    Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, Lee AT, Chung SA, Ferreira RC, Pant PV, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapää-Dahlqvist S, Petri M, Manzi S, Seldin MF, Rönnblom L, Syvänen AC, Criswell LA, Gregersen PK, Behrens TW (2008) Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358:900–909CrossRefPubMedGoogle Scholar
  64. 64.
    International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40:204–210CrossRefGoogle Scholar
  65. 65.
    McCarroll SA, Altshuler DM (2007) Copy-number variation and association studies of human disease. Nat Genet 39:S37–S42CrossRefPubMedGoogle Scholar
  66. 66.
    Carter NP (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet 39:S16–S21CrossRefPubMedGoogle Scholar
  67. 67.
    Schaschl H, Aitman TJ, Vyse TJ (2009) Copy number variation in the human genome and its implication in autoimmunity. Clin Exp Immunol 156:12–16CrossRefPubMedGoogle Scholar
  68. 68.
    Fanciulli M, Norsworthy PJ, Petretto E, Dong R, Harper L, Kamesh L, Heward JM, Gough SC, de Smith A, Blakemore AI, Froguel P, Owen CJ, Pearce SH, Teixeira L, Guillevin L, Graham DS, Pusey CD, Cook HT, Vyse TJ, Aitman TJ (2007) FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet 39:721–723CrossRefPubMedGoogle Scholar
  69. 69.
    de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramis G, Ballana E, Martin-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lazaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41:211–215CrossRefPubMedGoogle Scholar
  70. 70.
    Cheung VG, Spielman RS (2002) The genetics of variation in gene expression. Nat Genet 32(Suppl):522–525CrossRefPubMedGoogle Scholar
  71. 71.
    Schadt EE, Lamb J, Yang X, Zhu J, Edwards S, Guhathakurta D, Sieberts SK, Monks S, Reitman M, Zhang C, Lum PY, Leonardson A, Thieringer R, Metzger JM, Yang L, Castle J, Zhu H, Kash SF, Drake TA, Sachs A, Lusis AJ (2005) An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet 37:710–717CrossRefPubMedGoogle Scholar
  72. 72.
    Schadt EE (2009) Molecular networks as sensors and drivers of common human diseases. Nature 461:218–223CrossRefPubMedGoogle Scholar
  73. 73.
    Li B, Leal SM (2009) Discovery of rare variants via sequencing: implications for the design of complex trait association studies. PLoS Genet 5:e1000481CrossRefPubMedGoogle Scholar
  74. 74.
    Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH (2004) Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 305:869–872CrossRefPubMedGoogle Scholar
  75. 75.
    Romeo S, Pennacchio LA, Fu Y, Boerwinkle E, Tybjaerg-Hansen A, Hobbs HH, Cohen JC (2007) Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet 39:513–516CrossRefPubMedGoogle Scholar
  76. 76.
    Ji W, Foo JN, O’Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP (2008) Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40:592–599CrossRefPubMedGoogle Scholar
  77. 77.
    Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106:19096–19101CrossRefPubMedGoogle Scholar
  78. 78.
    Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42:30–35CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2010

Authors and Affiliations

  • Krzysztof Kiryluk
    • 1
  • Bruce A. Julian
    • 2
  • Robert J. Wyatt
    • 3
  • Francesco Scolari
    • 4
  • Hong Zhang
    • 5
  • Jan Novak
    • 2
  • Ali G. Gharavi
    • 1
  1. 1.Department of Medicine, Division of Nephrology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Departments of Microbiology and MedicineUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Division of Pediatric Nephrology, Department of Pediatrics, Children’s Foundation Research Center at the Le Bonheur Children’s Medical CenterUniversity of Tennessee Health Sciences CenterMemphisUSA
  4. 4.Division of NephrologyUniversità e Spedali CiviliBresciaItaly
  5. 5.Renal Division of First Hospital, Institute of NephrologyPeking UniversityBeijingChina

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