Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

AP HP Pediatric Nephrology Department Hôpital Robert Debré Paris France

Center for Data Sciences Brigham and Women's Hospital Harvard Medical School Boston MA USA

Centre for Genetics and Genomics Versus Arthritis University of Manchester Manchester UK

Croatian Academy of Medical Sciences Praska 2 3 p p 27 10000 Zagreb Croatia

Department of Advanced Pediatric Medicine Kobe University Graduate School of Medicine Kobe Japan

Department of Biochemistry and Molecular Biology University of Ulsan College of Medicine Songpa gu Seoul Korea

Department of Biomedical Informatics Harvard Medical School Boston MA USA

Department of Clinical Sciences and Community Health University of Milan Milan Italy

Department of Human Genetics Graduate School of Medicine The University of Tokyo Tokyo Japan

Department of Medical and Surgical Specialties Radiological Sciences and Public Health Division of Nephrology and Dialysis University of Brescia and ASST Spedali Civili of Brescia Brescia Italy

Department of Medicine Boston Children's Hospital Boston MA USA

Department of Nephrology and Renal Transplantation IRCCS Instituto Giannina Gaslini Genoa Italy

Department of Nephrology Centre Hospitalier du Mans Le Mans France

Department of Nephrology Dialysis and Transplant Unit University Hospital of Modena Modena Italy

Department of Nephrology Medicine and General University Hospital Charles University Prague Czech Republic

Department of Pediatric Division of Pediatric Nephrology Columbia University Irving Medical Center New York Presbyterian Morgan Stanley Children's Hospital in New York New York NY USA

Department of Pediatric Nephrology Amalia Children's Hospital Radboud University Medical Center Nijmegen The Netherlands

Department of Pediatric Nephrology Dialysis and Transplantation Clinical Hospital Hospital Center Zagreb University of Zagreb Medical School Zagreb Croatia

Department of Pediatric Nephrology UCLA Medical Center and UCLA Medical Center Santa Monica Los Angeles CA USA

Department of Pediatric Nephrology University Children's Hospital Skopje Macedonia

Department of Pediatric Nephrology VU University Medical Center Amsterdam The Netherlands

Department of Pediatrics AIIMS New Delhi India

Department of Pediatrics Faculty of Medicine Prince of Songkla University Hat Yai Songkhla 90110 Thailand

Department of Pediatrics Hallym University Sacred Heart Hospital 22 Gwanpyeong ro 170 beon gil Dongan gu Anyang si Gyeonggi do 14068 Korea

Department of Pediatrics Harvard Medical School Boston MA USA

Department of Pediatrics Interdisciplinary Laboratory of Medical Investigation Faculty of Medicine Federal University of Minas Gerais Belo Horizonte Brazil

Department of Pediatrics ISMETT Palermo Italy

Department of Pediatrics Kobe University Graduate School of Medicine Kobe Japan

Department of Pediatrics Nephrology and Hypertension Medical University Gdansk Gdansk Poland

Department of Pediatrics University of Split Split Croatia

Division of General Internal Medicine Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA

Division of Genomic Medicine Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA

Division of Nephrology and Dialysis Department of Pediatric Subspecialities Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù Rome Italy

Division of Nephrology and Dialysis Unit University of Messina Sicily Italy

Division of Nephrology and Pediatric Dialysis Bari Polyclinic Giovanni XXIII Children's Hospital Bari Italy

Division of Nephrology Beth Israel Deaconess Medical Center Boston MA USA

Division of Nephrology Boston Children's Hospital Boston MA USA

Division of Nephrology Department of Medicine Columbia University College of Physicians and Surgeons New York NY USA

Division of Renal Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA

Division of Transplantation Department of Surgery University of Pennsylvania Philadelphia PA USA

Divisions of Genetics and Rheumatology Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA

Genome Medical Science Project Tokyo Japan

Hyogo Prefectural Kobe Children's Hospital Kobe Japan

Institute for Genomic Health Icahn School of Medicine at Mount Sinai New York NY USA

Institute of Clinical Medicine Faculty of Medicine Vilnius University Vilnius Lithuania

Kennedy Institute of Rheumatology University of Oxford Roosevelt Drive Headington Oxford OX3 7FY United Kingdom

Kidney Disease Initiative and Medical and Population Genetics Program Broad Institute of MIT and Harvard Cambridge MA USA

Laboratory on Molecular Nephrology IRCCS Instituto Giannina Gaslini Genoa Italy

Nephrology Dialysis and Transplantation Unit Department of Emergency and Organ Transplantation University of Bari Aldo Moro Bari Italy

Pediatric Nephrology Dialysis and Transplant Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy

Pediatric Nephrology Hospital Universitari Vall d'Hebron Universitat Autónoma de Barcelona Barcelona Spain

Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA

Renal Diseases Research Unit Genetics and Rare Diseases Research Division Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù Rome Italy

Research and Clinical Institute for Pediatrics Pirogov Russian National Research Medical University Taldomskava St 2 Moscow Russia

Sorbonne Université UPMC Paris 06 Institut National de la Santé et de la Recherde Médicale Unité Mixte de Rechereche S 1155 Paris France

Surgical Medical and Dental Department of Morphological Sciences Section of Nephrology University of Modena and Reggio Emilia Modena Italy

The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York NY USA

Unità Operativa Nefrologia Azienda Ospedaliero Universitaria di Parma Dipartimento di Medicina e Chirurgia Università di Parma Parma Italy

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Kidney Int. 2024 Jan;105(1):14-17. doi: 10.1016/j.kint.2023.08.022. PubMed

See more in PubMed

Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018;392:61–74. doi: 10.1016/S0140-6736(18)30536-1. PubMed DOI

Gipson DS, et al. Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study. Health Qual. Life Outcomes. 2013;11:30. doi: 10.1186/1477-7525-11-30. PubMed DOI PMC

Ruth EM, Landolt MA, Neuhaus TJ, Kemper MJ. Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome. J. Pediatr. 2004;145:778–783. doi: 10.1016/j.jpeds.2004.08.022. PubMed DOI

Kerlin BA, et al. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study. J. Pediatr. 2009;155:105–110. doi: 10.1016/j.jpeds.2009.01.070. PubMed DOI PMC

Hingorani SR, Weiss NS, Watkins SL. Predictors of peritonitis in children with nephrotic syndrome. Pediatr. Nephrol. Berl. Ger. 2002;17:678–682. doi: 10.1007/s00467-002-0890-6. PubMed DOI

Rheault MN, et al. AKI in children hospitalized with nephrotic syndrome. Clin. J. Am. Soc. Nephrol. CJASN. 2015;10:2110–2118. doi: 10.2215/CJN.06620615. PubMed DOI PMC

Sato M, et al. Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study) Nephrol. Dial. Transplant. 2021;36:475–481. doi: 10.1093/ndt/gfz185. PubMed DOI

Ding WY, et al. Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence. J. Am. Soc. Nephrol. JASN. 2014;25:1342–1348. doi: 10.1681/ASN.2013080852. PubMed DOI PMC

Korsgaard T, Andersen RF, Joshi S, Hagstrøm S, Rittig S. Childhood onset steroid-sensitive nephrotic syndrome continues into adulthood. Pediatr. Nephrol. Berl. Ger. 2019;34:641–648. doi: 10.1007/s00467-018-4119-8. PubMed DOI

Ishikura K, et al. Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial. Pediatr. Nephrol. Berl. Ger. 2015;30:459–468. doi: 10.1007/s00467-014-2955-8. PubMed DOI

Fakhouri F, et al. Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am. J. Kidney Dis. J. Natl Kidney Found. 2003;41:550–557. doi: 10.1053/ajkd.2003.50116. PubMed DOI

Kyrieleis HAC, et al. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin. J. Am. Soc. Nephrol. CJASN. 2009;4:1593–1600. doi: 10.2215/CJN.05691108. PubMed DOI PMC

Skrzypczyk P, et al. Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood. Clin. Nephrol. 2014;81:166–173. doi: 10.5414/CN108044. PubMed DOI

Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS. Long-term outcome for children with minimal-change nephrotic syndrome. Lancet Lond. Engl. 1985;1:368–370. doi: 10.1016/S0140-6736(85)91387-X. PubMed DOI

Aydin M, et al. The long-term outcome of childhood nephrotic syndrome in Germany: a cross-sectional study. Clin. Exp. Nephrol. 2019;23:676–688. doi: 10.1007/s10157-019-01696-8. PubMed DOI

Lee JM, Kronbichler A, Shin JI, Oh J. Review on long-term non-renal complications of childhood nephrotic syndrome. Acta Paediatr. Oslo Nor. 1992. 2020;109:460–470. PubMed

Hjorten R, Anwar Z, Reidy KJ. Long-term outcomes of childhood onset nephrotic syndrome. Front. Pediatr. 2016;4:53. doi: 10.3389/fped.2016.00053. PubMed DOI PMC

Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet Lond. Engl. 1974;2:556–560. doi: 10.1016/S0140-6736(74)91880-7. PubMed DOI

Iijima K, Sako M, Kamei K, Nozu K. Rituximab in steroid-sensitive nephrotic syndrome: lessons from clinical trials. Pediatr. Nephrol. Berl. Ger. 2018;33:1449–1455. doi: 10.1007/s00467-017-3746-9. PubMed DOI PMC

Gbadegesin RA, et al. HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. J. Am. Soc. Nephrol. JASN. 2015;26:1701–1710. doi: 10.1681/ASN.2014030247. PubMed DOI PMC

Debiec H, et al. Transethnic, genome-wide analysis reveals immune-related risk alleles and phenotypic correlates in pediatric steroid-sensitive nephrotic syndrome. J. Am. Soc. Nephrol. JASN. 2018;29:2000–2013. doi: 10.1681/ASN.2017111185. PubMed DOI PMC

Jia X, et al. Strong association of the HLA-DR/DQ locus with childhood steroid-sensitive nephrotic syndrome in the japanese population. J. Am. Soc. Nephrol. JASN. 2018;29:2189–2199. doi: 10.1681/ASN.2017080859. PubMed DOI PMC

Jia X, et al. Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney Int. 2020;98:1308–1322. doi: 10.1016/j.kint.2020.05.029. PubMed DOI PMC

Dufek S, et al. Genetic identification of two novel loci associated with steroid-sensitive nephrotic syndrome. J. Am. Soc. Nephrol. JASN. 2019;30:1375–1384. doi: 10.1681/ASN.2018101054. PubMed DOI PMC

Julia A, et al. A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis. Hum. Mol. Genet. 2014;23:6927–6934. doi: 10.1093/hmg/ddu398. PubMed DOI

Schreiber TH, Podack ER. Immunobiology of TNFSF15 and TNFRSF25. Immunol. Res. 2013;57:3–11. doi: 10.1007/s12026-013-8465-0. PubMed DOI

Ovunc B, et al. Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patients. Nephron Clin. Pract. 2012;120:c139–c146. doi: 10.1159/000337379. PubMed DOI PMC

Mägi R, et al. Trans-ethnic meta-regression of genome-wide association studies accounting for ancestry increases power for discovery and improves fine-mapping resolution. Hum. Mol. Genet. 2017;26:3639–3650. doi: 10.1093/hmg/ddx280. PubMed DOI PMC

Ghoussaini M, et al. Open Targets Genetics: systematic identification of trait-associated genes using large-scale genetics and functional genomics. Nucleic Acids Res. 2021;49:D1311–D1320. doi: 10.1093/nar/gkaa840. PubMed DOI PMC

Ferland RJ, et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat. Genet. 2004;36:1008–1013. doi: 10.1038/ng1419. PubMed DOI

Kukimoto-Niino M, et al. Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex. Sci. Adv. 2021;7:eabg3147. doi: 10.1126/sciadv.abg3147. PubMed DOI PMC

Sharma KR, et al. ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions. Sci. Rep. 2016;6:37172. doi: 10.1038/srep37172. PubMed DOI PMC

Shimazaki A, et al. Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes. 2005;54:1171–1178. doi: 10.2337/diabetes.54.4.1171. PubMed DOI

Yu C-C, et al. Abatacept in B7-1–positive proteinuric kidney disease. N. Engl. J. Med. 2013;369:2416–2423. doi: 10.1056/NEJMoa1304572. PubMed DOI PMC

Spada R, et al. NKG2D ligand overexpression in lupus nephritis correlates with increased NK cell activity and differentiation in kidneys but not in the periphery. J. Leukoc. Biol. 2015;97:583–598. doi: 10.1189/jlb.4A0714-326R. PubMed DOI PMC

Rayego-Mateos S, et al. Role of epidermal growth factor receptor (EGFR) and its ligands in kidney inflammation and damage. Mediators Inflamm. 2018;2018:8739473. doi: 10.1155/2018/8739473. PubMed DOI PMC

Ju W, et al. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci. Transl. Med. 2015;7:316ra193. doi: 10.1126/scitranslmed.aac7071. PubMed DOI PMC

Rijvers L, et al. The Role of Autoimmunity-Related Gene CLEC16A in the B Cell Receptor-Mediated HLA Class II Pathway. J. Immunol. Baltim. Md 1950. 2020;205:945–956. PubMed

Tam RCY, et al. Human CLEC16A regulates autophagy through modulating mTOR activity. Exp. Cell Res. 2017;352:304–312. doi: 10.1016/j.yexcr.2017.02.017. PubMed DOI

Pearson G, et al. Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That Regulates β-Cell Mitophagy. Diabetes. 2018;67:265–277. doi: 10.2337/db17-0321. PubMed DOI PMC

Steimle V, Siegrist CA, Mottet A, Lisowska-Grospierre B, Mach B. Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science. 1994;265:106–109. doi: 10.1126/science.8016643. PubMed DOI

Edgar AJ, Birks EJ, Yacoub MH, Polak JM. Cloning of dexamethasone-induced transcript: a novel glucocorticoid-induced gene that is upregulated in emphysema. Am. J. Respir. Cell Mol. Biol. 2001;25:119–124. doi: 10.1165/ajrcmb.25.1.4417. PubMed DOI

Han, S. K. et al. Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs. Nat. Commun.14, 2229 (2023). PubMed PMC

GTEx Consortium, et al. Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation. Nat. Genet. 2018;50:956–967. doi: 10.1038/s41588-018-0154-4. PubMed DOI PMC

Schmiedel BJ, et al. Impact of genetic polymorphisms on human immune cell gene expression. Cell. 2018;175:1701–1715.e16. doi: 10.1016/j.cell.2018.10.022. PubMed DOI PMC

Fernández JM, et al. The BLUEPRINT data analysis portal. Cell Syst. 2016;3:491–495.e5. doi: 10.1016/j.cels.2016.10.021. PubMed DOI PMC

Li X, et al. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. J. Allergy Clin. Immunol. 2021;147:894–909. doi: 10.1016/j.jaci.2020.07.030. PubMed DOI PMC

Das, S., Miller, M. & Broide, D. H. Chromosome 17q21 Genes ORMDL3 and GSDMB in asthma and immune diseases. Adv. Immunol.135 1–52 (2017). PubMed

Corces MR, et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat. Genet. 2016;48:1193–1203. doi: 10.1038/ng.3646. PubMed DOI PMC

Muto Y, et al. Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney. Nat. Commun. 2021;12:2190. doi: 10.1038/s41467-021-22368-w. PubMed DOI PMC

Han, S. K. et al. Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model. Proc, Natl. Acad. Sci. USA 119, e2212810119 (2022). PubMed PMC

Luo, Y. et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ethnic fine-mapping in HIV host response. 10.1101/2020.07.16.20155606 (2020). PubMed PMC

Frommer L, Flesch BK, König J, Kahaly GJ. Amino acid polymorphisms in Hla class ii differentiate between thyroid and polyglandular autoimmunity. J. Clin. Endocrinol. Metab. 2020;105:dgz164. doi: 10.1210/clinem/dgz164. PubMed DOI

Badenhoop K, et al. Susceptibility and resistance alleles of human leukocyte antigen (HLA) DQA1 and HLA DQB1 are shared in endocrine autoimmune disease. J. Clin. Endocrinol. Metab. 1995;80:2112–2117. PubMed

Rodrigues CHM, Pires DEV, Ascher DB. DynaMut2: assessing changes in stability and flexibility upon single and multiple point missense mutations. Protein Sci. Publ. Protein Soc. 2021;30:60–69. doi: 10.1002/pro.3942. PubMed DOI PMC

Ren S, et al. Nephrotic syndrome associated with Kimura’s disease: a case report and literature review. BMC Nephrol. 2018;19:316. doi: 10.1186/s12882-018-1123-y. PubMed DOI PMC

Gallon L, Leventhal J, Skaro A, Kanwar Y, Alvarado A. Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. N. Engl. J. Med. 2012;366:1648–1649. doi: 10.1056/NEJMc1202500. PubMed DOI

Xu X, et al. Molecular insights into genome-wide association studies of chronic kidney disease-defining traits. Nat. Commun. 2018;9:4800. doi: 10.1038/s41467-018-07260-4. PubMed DOI PMC

Neale Lab. Relationship of LDSR Results with Sample Size. UKB Heritabilityhttps://nealelab.github.io/UKBB_ldsc/viz_sampsize.html (2022).

1000 Genomes Project Consortium. et al. A global reference for human genetic variation. Nature. 2015;526:68–74. doi: 10.1038/nature15393. PubMed DOI PMC

Wojcik GL, et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature. 2019;570:514–518. doi: 10.1038/s41586-019-1310-4. PubMed DOI PMC

Purcell S, et al. PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. Am. J. Hum. Genet. 2007;81:559–575. doi: 10.1086/519795. PubMed DOI PMC

Taliun, D. et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature,590, 290–299 (2021) PubMed PMC

Das S, et al. Next-generation genotype imputation service and methods. Nat. Genet. 2016;48:1284–1287. doi: 10.1038/ng.3656. PubMed DOI PMC

Fuchsberger C, Abecasis GR, Hinds DA. minimac2: faster genotype imputation. Bioinformatics. 2015;31:782–784. doi: 10.1093/bioinformatics/btu704. PubMed DOI PMC

Hinrichs AS, et al. The UCSC Genome Browser Database: update 2006. Nucleic Acids Res. 2006;34:D590–D598. doi: 10.1093/nar/gkj144. PubMed DOI PMC

Manichaikul A, et al. Robust relationship inference in genome-wide association studies. Bioinformatics. 2010;26:2867–2873. doi: 10.1093/bioinformatics/btq559. PubMed DOI PMC

Clarke L, et al. The international Genome sample resource (IGSR): a worldwide collection of genome variation incorporating the 1000 Genomes Project data. Nucleic Acids Res. 2017;45:D854–D859. doi: 10.1093/nar/gkw829. PubMed DOI PMC

Zhou W, et al. Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat. Genet. 2018;50:1335–1341. doi: 10.1038/s41588-018-0184-y. PubMed DOI PMC

Abraham G, Qiu Y, Inouye M. FlashPCA2: principal component analysis of Biobank-scale genotype datasets. Bioinformatics Oxf. Engl. 2017;33:2776–2778. doi: 10.1093/bioinformatics/btx299. PubMed DOI

Delaneau O, Marchini J, Zagury J-F. A linear complexity phasing method for thousands of genomes. Nat. Methods. 2011;9:179–181. doi: 10.1038/nmeth.1785. PubMed DOI

Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5:e1000529. doi: 10.1371/journal.pgen.1000529. PubMed DOI PMC

Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190–2191. doi: 10.1093/bioinformatics/btq340. PubMed DOI PMC

Pruim RJ, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26:2336–2337. doi: 10.1093/bioinformatics/btq419. PubMed DOI PMC

Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 2011;88:76–82. doi: 10.1016/j.ajhg.2010.11.011. PubMed DOI PMC

Yang J, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 2012;44:369–375. doi: 10.1038/ng.2213. PubMed DOI PMC

Bulik-Sullivan BK, et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 2015;47:291–295. doi: 10.1038/ng.3211. PubMed DOI PMC

Wen X, Pique-Regi R, Luca F. Integrating molecular QTL data into genome-wide genetic association analysis: probabilistic assessment of enrichment and colocalization. PLOS Genet. 2017;13:e1006646. doi: 10.1371/journal.pgen.1006646. PubMed DOI PMC

Gadegbeku CA, et al. Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach. Kidney Int. 2013;83:749–756. doi: 10.1038/ki.2012.428. PubMed DOI PMC

Wen X, Lee Y, Luca F, Pique-Regi R. Efficient integrative multi-SNP association analysis via deterministic approximation of posteriors. Am. J. Hum. Genet. 2016;98:1114–1129. doi: 10.1016/j.ajhg.2016.03.029. PubMed DOI PMC

Shi H, et al. Localizing components of shared transethnic genetic architecture of complex traits from GWAS summary data. Am. J. Hum. Genet. 2020;106:805–817. doi: 10.1016/j.ajhg.2020.04.012. PubMed DOI PMC

Maller JB, et al. Bayesian refinement of association signals for 14 loci in 3 common diseases. Nat. Genet. 2012;44:1294–1301. doi: 10.1038/ng.2435. PubMed DOI PMC

Ting YT, et al. A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease. Proc. Natl Acad. Sci. USA. 2020;117:3063–3073. doi: 10.1073/pnas.1914308117. PubMed DOI PMC

Mooers BHM. Shortcuts for faster image creation in PyMOL. Protein Sci. Publ. Protein Soc. 2020;29:268–276. doi: 10.1002/pro.3781. PubMed DOI PMC

Halgren TA. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comput. Chem. 1999;20:730–748. doi: 10.1002/(SICI)1096-987X(199905)20:7<730::AID-JCC8>3.0.CO;2-T. PubMed DOI

Johansson MU, Zoete V, Michielin O, Guex N. Defining and searching for structural motifs using DeepView/Swiss-PdbViewer. BMC Bioinformatics. 2012;13:173. doi: 10.1186/1471-2105-13-173. PubMed DOI PMC

Pol-Fachin L, Fernandes CL, Verli H. GROMOS96 43a1 performance on the characterization of glycoprotein conformational ensembles through molecular dynamics simulations. Carbohydr. Res. 2009;344:491–500. doi: 10.1016/j.carres.2008.12.025. PubMed DOI

Jubb HC, et al. Arpeggio: a web server for calculating and visualising interatomic interactions in protein structures. J. Mol. Biol. 2017;429:365–371. doi: 10.1016/j.jmb.2016.12.004. PubMed DOI PMC

Ruan Y, et al. Improving polygenic prediction in ancestrally diverse populations. Nat. Genet. 2022;54:573–580. doi: 10.1038/s41588-022-01054-7. PubMed DOI PMC

Ge T, Chen C-Y, Ni Y, Feng Y-CA, Smoller JW. Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nat. Commun. 2019;10:1776. doi: 10.1038/s41467-019-09718-5. PubMed DOI PMC