Hiding in plain sight: genetics of childhood steroid-resistant nephrotic syndrome in Sub-Saharan Africa

Banh TH, Hussain-Shamsy N, Patel V, Vasilevska-Ristovska J, Borges K, Sibbald C, Lipszyc D, Brooke J, Geary D, Langlois V, Reddon M, Pearl R, Levin L, Piekut M, Licht CP, Radhakrishnan S, Aitken-Menezes K, Harvey E, Hebert D, Piscione TD, Parekh RS (2016) Ethnic differences in incidence and outcomes of childhood nephrotic syndrome. Clin J Am Soc Nephrol 11:1760–1768 Chanchlani R, Parekh RS (2016) Ethnic differences in childhood nephrotic syndrome. Front Pediatr 4:39 Noone DG, Iijima K, Parekh R (2018) Idiopathic nephrotic syndrome in children. Lancet 392:61–74 Wong W (2007) Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health 43:337–341 McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM (2001) Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol 16:1040–1044 Olowu WA, Adelusola KA, Adefehinti O (2010) Reversed clinical and morphologic characteristics of idiopathic childhood nephrotic syndrome. Int J Nephro Urol 2:200–211 Anochie I, Eke F, Okpere A (2006) Childhood nephrotic syndrome: change in pattern and response to steroids. J Natl Med Assoc 98:1977–1981 Ladapo TA, Esezobor CI, Lesi FE (2014) High steroid sensitivity among children with nephrotic syndrome in Southwestern Nigeria. Int J Nephrol 2014:350640 Olowu WA, Adelusola KA, Adefehinti O (2010) Childhood idiopathic steroid resistant nephrotic syndrome in Southwestern Nigeria. Saudi J Kidney Dis Transpl 21:979–990 Mekahli D, Liutkus A, Ranchin B, Yu A, Bessenay L, Girardin E, Van Damme-Lombaerts R, Palcoux JB, Cachat F, Lavocat MP, Bourdat-Michel G, Nobili F, Cochat P (2009) Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study. Pediatr Nephrol 24:1525–1532 Inaba A, Hamasaki Y, Ishikura K, Hamada R, Sakai T, Hataya H, Komaki F, Kaneko T, Mori M, Honda M (2016) Long-term outcome of idiopathic steroid-resistant nephrotic syndrome in children. Pediatr Nephrol 31:425–434 Trautmann A, Schnaidt S, Lipska-Ziętkiewicz BS, Bodria M, Ozaltin F, Emma F, Anarat A, Melk A, Azocar M, Oh J, Saeed B, Gheisari A, Caliskan S, Gellermann J, Higuita LMS, Jankauskiene A, Drozdz D, Mir S, Balat A, Szczepanska M, Paripovic D, Zurowska A, Bogdanovic R, Yilmaz A, Ranchin B, Baskin E, Erdogan O, Remuzzi G, Firszt-Adamczyk A, Kuzma-Mroczkowska E, Litwin M, Murer L, Tkaczyk M, Jardim H, Wasilewska A, Printza N, Fidan K, Simkova E, Borzecka H, Staude H, Hees K, Schaefer F, PodoNet Consortium (2017) Long-term outcome of steroid-resistant nephrotic syndrome in children. J Am Soc Nephrol 28:3055–3065 Büscher AK, Beck BB, Melk A, Hoefele J, Kranz B, Bamborschke D, Baig S, Lange-Sperandio B, Jungraithmayr T, Weber LT, Kemper MJ, Tönshoff B, Hoyer PF, Konrad M, Weber S, German Pediatric Nephrology Association (GPN) (2016) Rapid response to cyclosporin A and favorable renal outcome in non genetic versus genetic steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 11:245–253 Ingulli E, Tejani A (1991) Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol 5:393–397 Nandlal L, Naicker T, Bhimma R (2019) Nephrotic syndrome in South African children: changing perspectives in the new millennium. Kidney Int Rep 4:522–534 Kim JS, Bellew CA, Silverstein DM, Aviles DH, Boineau FG, Vehaskari VM (2005) High incidence of initial and late steroid resistance in childhood nephrotic syndrome. Kidney Int 68:1275–1281 Bakhiet YM, Mudi A, Khumalo T, Moonsamy G, Levy C (2017) Idiopathic nephrotic syndrome in South African children. Afr Health Sci 17:1130–1136 Wine R, Vasilevska-Ristovska J, Banh T, Knott J, Noone D, Gbadegesin R, Ilori TO, Okafor HU, Furia F, Ulasi I, Solarin AU, Esezobor C, Batte A, Raji Y, Olanrewaju TO, Muoneke U, Adetunji AE, Boima V, Amira O, Osafo C, Guemkam G, Ajayi S, Makusidi MA, Anigilaje EA, Ruggajo P, Asinobi AO, Ademola AD, Parekh RS, the H3 Africa Kidney Disease Research Network (2021) Trends in the epidemiology of childhood nephrotic syndrome in Africa: a systematic review. Glob Epidemiol 3:e100061 Olowu WA, Ademola A, Ajite AB, Saad YM (2017) Childhood nephrotic syndrome in tropical Africa: then and now. Paediatr Int Child Health 37:259–268 Esezobor CI, Solarin AU, Gbadegesin R (2020) Changing epidemiology of nephrotic syndrome in Nigerian children: a cross-sectional study. PLoS One 15:e0239300 Konstantelos N, Banh T, Patel V, Vasilevska-Ristovska J, Borges K, Hussain-Shamsy N, Noone D, Hebert D, Radhakrishnan S, Licht CPB, Langlois V, Pearl RJ, Parekh RS (2019) Association of low birth weight and prematurity with clinical outcomes of childhood nephrotic syndrome: a prospective cohort study. Pediatr Nephrol 34:1599–1605 Teeninga N, Schreuder MF, Bökenkamp A, Delemarre-van de Waal HA, van Wijk JA (2008) Influence of low birth weight on minimal change nephrotic syndrome in children, including a meta-analysis. Nephrol Dial Transplant 23:1615–1620 Conti G, De Vivo D, Fede C, Arasi S, Alibrandi A, Chimenz R, Santoro D (2018) Low birth weight is a conditioning factor for podocyte alteration and steroid dependance in children with nephrotic syndrome. J Nephrol 31:411–415 Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59:1498–1509 GBD 2017 HIV collaborators (2017) HIV collaborators (2019) Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Lancet HIV 6:e831–e859 Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN (2013) Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLoS Med 10:e1001484 Bhimma R, Adhikari M, Asharam K, Connolly C (2008) The spectrum of chronic kidney disease (stages 2–5) in KwaZulu-Natal. South Africa Pediatr Nephrol 23:1841–1846 el Ali TM, Abdelraheem MB, Mohamed RM, Hassan EG, Watson AR (2009) Chronic renal failure in Sudanese children: aetiology and outcomes. Pediatr Nephrol 24:349–353 Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, Engelmann S, Vega-Warner V, Fang H, Halbritter J, Somers MJ, Tan W, Shril S, Fessi I, Lifton RP, Bockenhauer D, El-Desoky S, Kari JA, Zenker M, Kemper MJ, Mueller D, Fathy HM, Soliman NA, SRNS Study Group, Hildebrandt F (2015) A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 26:1279–1289 Bensimhon AR, Williams AE, Gbadegesin RA (2019) Treatment of steroid-resistant nephrotic syndrome in the genomic era. Pediatr Nephrol 34:2279–2293 Trautmann A, Lipska-Ziętkiewicz BS, Schaefer F (2018) Exploring the clinical and genetic spectrum of steroid resistant nephrotic syndrome: the PodoNet Registry. Front Pediatr 6:200 Kopp JB, Anders HJ, Susztak K, Podestà MA, Remuzzi G, Hildebrandt F, Romagnani P (2020) Podocytopathies Nat Rev Dis Primers 6:68 Voskarides K, Damianou L, Neocleous V, Zouvani I, Christodoulidou S, Hadjiconstantinou V, Ioannou K, Athanasiou Y, Patsias C, Alexopoulos E, Pierides A, Kyriacou K, Deltas C (2007) COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy. J Am Soc Nephrol 18:3004–3016 Malone AF, Phelan PJ, Hall G, Cetincelik U, Homstad A, Alonso AS, Jiang R, Lindsey TB, Wu G, Sparks MA, Smith SR, Webb NJ, Kalra PA, Adeyemo AA, Shaw AS, Conlon PJ, Jennette JC, Howell DN, Winn MP, Gbadegesin RA (2014) Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int 86:1253–1259 Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998) Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell 1:575–582 Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C (2000) NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 24:349–354 Gbadegesin RA, Adeyemo A, Webb NJ, Greenbaum LA, Abeyagunawardena A, Thalgahagoda S, Kale A, Gipson D, Srivastava T, Lin JJ, Chand D, Hunley TE, Brophy PD, Bagga A, Sinha A, Rheault MN, Ghali J, Nicholls K, Abraham E, Janjua HS, Omoloja A, Barletta GM, Cai Y, Milford DD, O’Brien C, Awan A, Belostotsky V, Smoyer WE, Homstad A, Hall G, Wu G, Nagaraj S, Wigfall D, Foreman J, Winn MP, Mid-West Pediatric Nephrology Consortium (2015) HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. J Am Soc Nephrol 26:1701–1710 Debiec H, Dossier C, Letouzé E, Gillies CE, Vivarelli M, Putler RK, Ars E, Jacqz-Aigrain E, Elie V, Colucci M, Debette S, Amouyel P, Elalaoui SC, Sefiani A, Dubois V, Simon T, Kretzler M, Ballarin J, Emma F, Sampson MG, Deschênes G, Ronco P (2018) Transethnic, Genome-wide analysis reveals immune-related risk alleles and phenotypic correlates in pediatric steroid-sensitive nephrotic syndrome. J Am Soc Nephrol 29:2000–2013 Dufek S, Cheshire C, Levine AP, Trompeter RS, Issler N, Stubbs M, Mozere M, Gupta S, Klootwijk E, Patel V, Hothi D, Waters A, Webb H, Tullus K, Jenkins L, Godinho L, Levtchenko E, Wetzels J, Knoers N, Teeninga N, Nauta J, Shalaby M, Eldesoky S, Kari JA, Thalgahagoda S, Ranawaka R, Abeyagunawardena A, Adeyemo A, Kristiansen M, Gbadegesin R, Webb NJ, Gale DP, Stanescu HC, Kleta R, Bockenhauer D (2019) Genetic identification of two novel loci associated with steroid-sensitive nephrotic syndrome. J Am Soc Nephrol 30:1375–1384 Jia X, Yamamura T, Gbadegesin R, McNulty MT, Song K, Nagano C, Hitomi Y, Lee D, Aiba Y, Khor SS, Ueno K, Kawai Y, Nagasaki M, Noiri E, Horinouchi T, Kaito H, Hamada R, Okamoto T, Kamei K, Kaku Y, Fujimaru R, Tanaka R, Shima Y, Research Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in Japan, Baek J, Kang HG, Ha IS, Han KH, Yang EM, Korean Consortium of Hereditary Renal Diseases in Children, Abeyagunawardena A, Lane B, Chryst-Stangl M, Esezobor C, Solarin A, Midwest Pediatric Nephrology Consortium (Genetics of Nephrotic Syndrome Study Group), Dossier C, Deschênes G, NEPHROVIR, Vivarelli M, Debiec H, Ishikura K, Matsuo M, Nozu K, Ronco P, Cheong HI, Sampson MG, Tokunaga K, Iijima K (2020) Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney Int 98:1308–1322 Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, Baslund B, Brenchley P, Bruchfeld A, Chaudhry AN, Cohen Tervaert JW, Deloukas P, Feighery C, Gross WL, Guillevin L, Gunnarsson I, Harper L, Hrušková Z, Little MA, Martorana D, Neumann T, Ohlsson S, Padmanabhan S, Pusey CD, Salama AD, Sanders JS, Savage CO, Segelmark M, Stegeman CA, Tesař V, Vaglio A, Wieczorek S, Wilde B, Zwerina J, Rees AJ, Clayton DG, Smith KG (2012) Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 367:214–223 Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329:841–845 Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP (2011) Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 43:321–327 Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, Fasel D, Lata S, Prakash S, Shapiro S, Fischman C, Snyder HJ, Appel G, Izzi C, Viola BF, Dallera N, Del Vecchio L, Barlassina C, Salvi E, Bertinetto FE, Amoroso A, Savoldi S, Rocchietti M, Amore A, Peruzzi L, Coppo R, Salvadori M, Ravani P, Magistroni R, Ghiggeri GM, Caridi G, Bodria M, Lugani F, Allegri L, Delsante M, Maiorana M, Magnano A, Frasca G, Boer E, Boscutti G, Ponticelli C, Mignani R, Marcantoni C, Di Landro D, Santoro D, Pani A, Polci R, Feriozzi S, Chicca S, Galliani M, Gigante M, Gesualdo L, Zamboli P, Battaglia GG, Garozzo M, Maixnerová D, Tesar V, Eitner F, Rauen T, Floege J, Kovacs T, Nagy J, Mucha K, Pączek L, Zaniew M, Mizerska-Wasiak M, Roszkowska-Blaim M, Pawlaczyk K, Gale D, Barratt J, Thibaudin L, Berthoux F, Canaud G, Boland A, Metzger M, Panzer U, Suzuki H, Goto S, Narita I, Caliskan Y, Xie J, Hou P, Chen N, Zhang H, Wyatt RJ, Novak J, Julian BA, Feehally J, Stengel B, Cusi D, Lifton RP, Gharavi AG (2014) Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46:1187–1196 Li M, Foo JN, Wang JQ, Low HQ, Tang XQ, Toh KY, Yin PR, Khor CC, Goh YF, Irwan ID, Xu RC, Andiappan AK, Bei JX, Rotzschke O, Chen MH, Cheng CY, Sun LD, Jiang GR, Wong TY, Lin HL, Aung T, Liao YH, Saw SM, Ye K, Ebstein RP, Chen QK, Shi W, Chew SH, Chen J, Zhang FR, Li SP, Xu G, Shyong Tai E, Wang L, Chen N, Zhang XJ, Zeng YX, Zhang H, Liu ZH, Yu XQ, Liu JJ (2015) Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nat Commun 6:7270 Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, Patel N, Pearce K, Hubank M, Stephens HA, Laundy V, Padmanabhan S, Zawadzka A, Hofstra JM, Coenen MJ, den Heijer M, Kiemeney LA, Bacq-Daian D, Stengel B, Powis SH, Brenchley P, Feehally J, Rees AJ, Debiec H, Wetzels JF, Ronco P, Mathieson PW, Kleta R (2011) Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 364:616–626 Xie J, Liu L, Mladkova N, Li Y, Ren H, Wang W, Cui Z, Lin L, Hu X, Yu X, Xu J, Liu G, Caliskan Y, Sidore C, Balderes O, Rosen RJ, Bodria M, Zanoni F, Zhang JY, Krithivasan P, Mehl K, Marasa M, Khan A, Ozay F, Canetta PA, Bomback AS, Appel GB, Sanna-Cherchi S, Sampson MG, Mariani LH, Perkowska-Ptasinska A, Durlik M, Mucha K, Moszczuk B, Foroncewicz B, Pączek L, Habura I, Ars E, Ballarin J, Mani LY, Vogt B, Ozturk S, Yildiz A, Seyahi N, Arikan H, Koc M, Basturk T, Karahan G, Akgul SU, Sever MS, Zhang D, Santoro D, Bonomini M, Londrino F, Gesualdo L, Reiterova J, Tesar V, Izzi C, Savoldi S, Spotti D, Marcantoni C, Messa P, Galliani M, Roccatello D, Granata S, Zaza G, Lugani F, Ghiggeri G, Pisani I, Allegri L, Sprangers B, Park JH, Cho B, Kim YS, Kim DK, Suzuki H, Amoroso A, Cattran DC, Fervenza FC, Pani A, Hamilton P, Harris S, Gupta S, Cheshire C, Dufek S, Issler N, Pepper RJ, Connolly J, Powis S, Bockenhauer D, Stanescu HC, Ashman N, Loos RJF, Kenny EE, Wuttke M, Eckardt KU, Köttgen A, Hofstra JM, Coenen MJH, Kiemeney LA, Akilesh S, Kretzler M, Beck LH, Stengel B, Debiec H, Ronco P, Wetzels JFM, Zoledziewska M, Cucca F, Ionita-Laza I, Lee H, Hoxha E, Stahl RAK, Brenchley P, Scolari F, Zhao MH, Gharavi AG, Kleta R, Chen N, Kiryluk K (2020) The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nat Commun 11:1600 Wiggins RC (2007) The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 71:1205–1214 Varner JD, Chryst-Stangl M, Esezobor CI, Solarin A, Wu G, Lane B, Hall G, Abeyagunawardena A, Matory A, Hunley TE, Lin JJ, Howell D, Gbadegesin R (2018) Genetic testing for steroid-resistant-nephrotic syndrome in an outbred population. Front Pediatr 6:307 Choy J, Kan Y, Cifelli S, Johnson J, Chen M, Shiao LL, Zhou H, Previs S, Lei Y, Johnstone R, Liaw A, Saigal A, Hu L, Ramos R, Visconti R, McElroy WT, Kreamer A, Wildey MJ, Peier A, Shin MK, Imbriglio J, Ren Z, Hoek M, Weinglass A, Ai X (2021) High-throughput screening to identify small molecules that selectively inhibit APOL1 protein level in podocytes. SLAS Discov 26:1225–1237 Azevedo MJ (2017) The state of health system(s) in Africa: challenges and opportunities. (Azevedo MJ) Historical perspectives on the state of health and health systems in Africa, vol II. African Histories and Modernities. Palgrave Macmillan, London, pp 1–73 Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM (2010) Complete Khoisan and Bantu genomes from southern Africa. Nature 463:943–947 McEvoy BP, Powell JE, Goddard ME, Visscher PM (2011) Human population dispersal “Out of Africa” estimated from linkage disequilibrium and allele frequencies of SNPs. Genome Res 21:821–829 Chan EKF, Timmermann A, Baldi BF, Moore AE, Lyons RJ, Lee SS, Kalsbeek AMF, Petersen DC, Rautenbach H, Förtsch HEA, Bornman MSR, Hayes VM (2019) Human origins in a southern African palaeo-wetland and first migrations. Nature 575:185–189 Collins RL, Brand H, Karczewski KJ, Zhao X, Alföldi J, Francioli LC, Khera AV, Lowther C, Gauthier LD, Wang H, Watts NA, Solomonson M, O’Donnell-Luria A, Baumann A, Munshi R, Walker M, Whelan CW, Huang Y, Brookings T, Sharpe T, Stone MR, Valkanas E, Fu J, Tiao G, Laricchia KM, Ruano-Rubio V, Stevens C, Gupta N, Cusick C, Margolin L; Genome Aggregation Database Production Team; Genome Aggregation Database Consortium, Taylor KD, Lin HJ, Rich SS, Post WS, Chen YI, Rotter JI, Nusbaum C, Philippakis A, Lander E, Gabriel S, Neale BM, Kathiresan S, Daly MJ, Banks E, MacArthur DG, Talkowski ME (2020) A structural variation reference for medical and population genetics. Nature 581:444–451 Lipson M, Sawchuk EA, Thompson JC, Oppenheimer J, Tryon CA, Ranhorn KL, de Luna KM, Sirak KA, Olalde I, Ambrose SH, Arthur JW, Arthur KJW, Ayodo G, Bertacchi A, Cerezo-Román JI, Culleton BJ, Curtis MC, Davis J, Gidna AO, Hanson A, Kaliba P, Katongo M, Kwekason A, Laird MF, Lewis J, Mabulla AZP, Mapemba F, Morris A, Mudenda G, Mwafulirwa R, Mwangomba D, Ndiema E, Ogola C, Schilt F, Willoughby PR, Wright DK, Zipkin A, Pinhasi R, Kennett DJ, Manthi FK, Rohland N, Patterson N, Reich D, Prendergast ME (2022) Ancient DNA and deep population structure in sub-Saharan African foragers. Nature 603:290–296 Gomez F, Hirbo J, Tishkoff SA (2014) Genetic variation and adaptation in Africa: implications for human evolution and disease. Cold Spring Harb Perspect Biol 6:a008524 Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434–443 Gudmundsson S, Singer-Berk M, Watts NA, Phu W, Goodrich JK, Solomonson M, Genome Aggregation Database Consortium, Rehm HL, MacArthur DG, O’Donnell-Luria A (2021) Variant interpretation using population databases: lessons from gnomAD. Hum Mutat 43:1012–1030 Asharam K, Bhimma R, David VA, Coovadia HM, Qulu WP, Naicker T, Gillies CE, Vega-Warner V, Johnson RC, Limou S, Kopp JB, Sampson M, Nelson GW, Winkler CA (2018) NPHS2 V260E is a frequent cause of steroid-resistant nephrotic syndrome in black South African children. Kidney Int Rep 3:1354–1362 Govender MA, Fabian J, Gottlich E, Levy C, Moonsamy G, Maher H, Winkler CA, Ramsay M (2019) The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis. Commun Biol 2:416 Tang X, Brown MR, Cogal AG, Gauvin D, Harris PC, Lieske JC, Romero MF, Chang MH (2016) Functional and transport analyses of CLCN5 genetic changes identified in Dent disease patients. Physiol Rep 4:e12776 Olabisi OA, Zhang JY, VerPlank L, Zahler N, DiBartolo S 3rd, Heneghan JF, Schlöndorff JS, Suh JH, Yan P, Alper SL, Friedman DJ, Pollak MR (2016) APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases. Proc Natl Acad Sci U S A 113:830–837 Datta S, Kataria R, Zhang JY, Moore S, Petitpas K, Mohamed A, Zahler N, Pollak MR, Olabisi OA (2020) Kidney disease-associated APOL1 variants have dose-dependent, dominant toxic gain-of-function. J Am Soc Nephrol 31:2083–2096 Woroniecki RP, Ng DK, Limou S, Winkler CA, Reidy KJ, Mitsnefes M, Sampson MG, Wong CS, Warady BA, Furth SL, Kopp JB, Kaskel FJ (2016) Renal and cardiovascular morbidities associated with APOL1 status among African-American and non-African-American children with focal segmental glomerulosclerosis. Front Pediatr 4:122 Sampson MG, Robertson CC, Martini S, Mariani LH, Lemley KV, Gillies CE, Otto EA, Kopp JB, Randolph A, Vega-Warner V, Eichinger F, Nair V, Gipson DS, Cattran DC, Johnstone DB, O’Toole JF, Bagnasco SM, Song PX, Barisoni L, Troost JP, Kretzler M, Sedor JR, Nephrotic Syndrome Study Network (2016) Integrative genomics identifies novel associations with APOL1 risk genotypes in black NEPTUNE subjects. J Am Soc Nephrol 27:814–823 Gribouval O, Boyer O, Knebelmann B, Karras A, Dantal J, Fourrage C, Alibeu O, Hogan J, Dossier C, Tête MJ, Antignac C, Servais A (2019) APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries. Nephrol Dial Transplant 34:1885–1893 Kopp JB, Winkler CA, Zhao X, Radeva MK, Gassman JJ, D’Agati VD, Nast CC, Wei C, Reiser J, Guay-Woodford LM, Pollak MR, Hildebrandt F, Moxey-Mims M, Gipson DS, Trachtman H, Friedman AL, Kaskel FJ, FSGS-CT Study Consortium (2015) Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS clinical trial. J Am Soc Nephrol 26:1443–1448 Adeyemo A, Esezobor C, Solarin A, Abeyagunawardena A, Kari JA, El Desoky S, Greenbaum LA, Kamel M, Kallash M, Silva C, Young A, Hunley TE, de Jesus-Gonzalez N, Srivastava T, Gbadegesin R (2018) HLA-DQA1 and APOL1 as risk loci for childhood-onset steroid-sensitive and steroid-resistant nephrotic syndrome. Am J Kidney Dis 71:399–406 Ng DK, Robertson CC, Woroniecki RP, Limou S, Gillies CE, Reidy KJ, Winkler CA, Hingorani S, Gibson KL, Hjorten R, Sethna CB, Kopp JB, Moxey-Mims M, Furth SL, Warady BA, Kretzler M, Sedor JR, Kaskel FJ, Sampson MG (2017) APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts. Nephrol Dial Transplant 32:983–990 Watanabe A, Guaragna MS, Belangero VMS, Casimiro FMS, Pesquero JB, de Santis FL, Palma LMP, Varela P, de Menezes Neves PDM, Lerario AM, de Souza ML, de Mello MP, de Brito Lutaif ACG, Ferrari CR, Sampson MG, Onuchic LF, Nogueira PCK (2021) APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses. Pediatr Nephrol 36:2327–2336 H3Africa Consortium, Rotimi C, Abayomi A, Abimiku A, Adabayeri VM, Adebamowo C, Adebiyi E, Ademola AD, Adeyemo A, Adu D, Affolabi D, Agongo G, Ajayi S, Akarolo- Anthony S, Akinyemi R, Akpalu A, Alberts M, Alonso Betancourt O, Alzohairy AM, Ameni G, Amodu O, Anabwani G, Andersen K, Arogundade F, Arulogun O, Asogun D, Bakare R, Balde N, Baniecki ML, Beiswanger C, Benkahla A, Bethke L, Boehnke M, Boima V, Brandful J, Brooks AI, Brosius FC, Brown C, Bucheton B, Burke DT, Burnett BG, Carrington-Lawrence S, Carstens N, Chisi J, Christoffels A, Cooper R, Cordell H, Crowther N, Croxton T, de Vries J, Derr L, Donkor P, Doumbia S, Duncanson A, Ekem I, El Sayed A, Engel ME, Enyaru JC, Everett D, Fadlelmola FM, Fakunle E, Fischbeck KH, Fischer A, Folarin O, Gamieldien J, Garry RF, Gaseitsiwe S, Gbadegesin R, Ghansah A, Giovanni M, Goesbeck P, Gomez-Olive FX, Grant DS, Grewal R, Guyer M, Hanchard NA, Happi CT, Hazelhurst S, Hennig BJ, Hertz- C, Fowler, Hide W, Hilderbrandt F, Hugo-Hamman C, Ibrahim ME, James R, Jaufeerally-Fakim Y, Jenkins C, Jentsch U, Jiang PP, Joloba M, Jongeneel V, Joubert F, Kader M, Kahn K, Kaleebu P, Kapiga SH, Kassim SK, Kasvosve I, Kayondo J, Keavney B, Kekitiinwa A, Khan SH, Kimmel P, King MC, Kleta R, Koffi M, Kopp J, Kretzler M, Kumuthini J, Kyobe S, Kyobutungi C, Lackland DT, Lacourciere KA, Landouré G, Lawlor R, Lehner T, Lesosky M, Levitt N, Littler K, Lombard Z, Loring JF, Lyantagaye S, Macleod A, Madden EB, Mahomva CR, Makani J, Mamven M, Marape M, Mardon G, Marshall P, Martin DP, Masiga D, Mason R, Mate-Kole M, Matovu E, Mayige M, Mayosi BM, Mbanya JC, McCurdy SA, McCarthy MI, McIlleron H, Mc’Ligeyo SO, Merle C, Mocumbi AO, Mondo C, Moran JV, Motala A, Moxey-Mims M, Mpoloka WS, Msefula CL, Mthiyane T, Mulder N, Mulugeta Gh, Mumba D, Musuku J, Nagdee M, Nash O, Ndiaye D, Nguyen AQ, Nicol M, Nkomazana O, Norris S, Nsangi B, Nyarko A, Nyirenda M, Obe E, Obiakor R, Oduro A, Ofori-Acquah SF, Ogah O, Ogendo S, Ohene-Frempong K, Ojo A, Olanrewaju T, Oli J, Osafo C, Ouwe Missi Oukem-Boyer O, Ovbiagele B, Owen A, Owolabi MO, Owolabi L, Owusu-Dabo E, Pare G, Parekh R, Patterton HG, Penno MB, Peterson J, Pieper R, Plange-Rhule J, Pollak M, Puzak J, Ramesar RS, Ramsay M, Rasooly R, Reddy S, Sabeti PC, Sagoe K, Salako T, Samassékou O, Sandhu MS, Sankoh O, SarfoFS, Sarr M, Shaboodien G, Sidibe I, Simo G, Simuunza M, Smeeth L, Sobngwi E, Soodyall H, Sorgho H, Sow Bah O, Srinivasan S, Stein DJ, Susser ES, Swanepoel C, Tangwa G, Tareila A, Tastan Bishop O, Tayo B, Tiffin N, Tinto H, Tobin E, Tollman SM, Traoré M, Treadwell MJ, Troyer J, Tsimako-Johnstone M, Tukei V, Ulasi I, Ulenga N, van Rooyen B, Wachinou AP, Waddy SP, Wade A, Wayengera M, Whitworth J, Wideroff L, Winkler CA, Winnicki S, Wonkam A, Yewondwos M, sen T, Yozwiak N, Zar H (2014) Research capacity Enabling the genomic revolution in Africa. Science 344:1346–1348 Adu D, Ojo A, H3A-KDRN Investigators (2020) Overview of the Human Heredity and Health in Africa Kidney Disease Research Network (H3A-KDRN). Kidney360 2(1):129–133