Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

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Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. / Barry, Alexandra; McNulty, Michelle T.; Jia, Xiaoyuan; Gupta, Yask; Debiec, Hanna; Luo, Yang; Nagano, China; Horinouchi, Tomoko; Jung, Seulgi; Colucci, Manuela; Ahram, Dina F.; Mitrotti, Adele; Sinha, Aditi; Teeninga, Nynke; Jin, Gina; Shril, Shirlee; Caridi, Gianluca; Bodria, Monica; Lim, Tze Y.; Westland, Rik; Zanoni, Francesca; Marasa, Maddalena; Turudic, Daniel; Giordano, Mario; Gesualdo, Loreto; Magistroni, Riccardo; Pisani, Isabella; Fiaccadori, Enrico; Reiterova, Jana; Maringhini, Silvio; Morello, William; Montini, Giovanni; Weng, Patricia L.; Scolari, Francesco; Saraga, Marijan; Tasic, Velibor; Santoro, Domenica; van Wijk, Joanna A.E.; Milošević, Danko; Kawai, Yosuke; Kiryluk, Krzysztof; Pollak, Martin R.; Gharavi, Ali; Lin, Fangmin; Simœs e Silva, Ana Cristina; Loos, Ruth J.F.; Kenny, Eimear E.; Schreuder, Michiel F.; Zurowska, Aleksandra; Dossier, Claire; Ariceta, Gema; Drozynska-Duklas, Magdalena; Hogan, Julien; Jankauskiene, Augustina; Hildebrandt, Friedhelm; Prikhodina, Larisa; Song, Kyuyoung; Bagga, Arvind; Cheong, Hae; Ghiggeri, Gian Marco; Vachvanichsanong, Prayong; Nozu, Kandai; Lee, Dongwon; Vivarelli, Marina; Raychaudhuri, Soumya; Tokunaga, Katsushi; Sanna-Cherchi, Simone; Ronco, Pierre; Iijima, Kazumoto; Sampson, Matthew G.

I: Nature Communications, Bind 14, Nr. 1, 2481, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Barry, A, McNulty, MT, Jia, X, Gupta, Y, Debiec, H, Luo, Y, Nagano, C, Horinouchi, T, Jung, S, Colucci, M, Ahram, DF, Mitrotti, A, Sinha, A, Teeninga, N, Jin, G, Shril, S, Caridi, G, Bodria, M, Lim, TY, Westland, R, Zanoni, F, Marasa, M, Turudic, D, Giordano, M, Gesualdo, L, Magistroni, R, Pisani, I, Fiaccadori, E, Reiterova, J, Maringhini, S, Morello, W, Montini, G, Weng, PL, Scolari, F, Saraga, M, Tasic, V, Santoro, D, van Wijk, JAE, Milošević, D, Kawai, Y, Kiryluk, K, Pollak, MR, Gharavi, A, Lin, F, Simœs e Silva, AC, Loos, RJF, Kenny, EE, Schreuder, MF, Zurowska, A, Dossier, C, Ariceta, G, Drozynska-Duklas, M, Hogan, J, Jankauskiene, A, Hildebrandt, F, Prikhodina, L, Song, K, Bagga, A, Cheong, H, Ghiggeri, GM, Vachvanichsanong, P, Nozu, K, Lee, D, Vivarelli, M, Raychaudhuri, S, Tokunaga, K, Sanna-Cherchi, S, Ronco, P, Iijima, K & Sampson, MG 2023, 'Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome', Nature Communications, bind 14, nr. 1, 2481. https://doi.org/10.1038/s41467-023-37985-w

APA

Barry, A., McNulty, M. T., Jia, X., Gupta, Y., Debiec, H., Luo, Y., Nagano, C., Horinouchi, T., Jung, S., Colucci, M., Ahram, D. F., Mitrotti, A., Sinha, A., Teeninga, N., Jin, G., Shril, S., Caridi, G., Bodria, M., Lim, T. Y., ... Sampson, M. G. (2023). Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. Nature Communications, 14(1), [2481]. https://doi.org/10.1038/s41467-023-37985-w

Vancouver

Barry A, McNulty MT, Jia X, Gupta Y, Debiec H, Luo Y o.a. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. Nature Communications. 2023;14(1). 2481. https://doi.org/10.1038/s41467-023-37985-w

Author

Barry, Alexandra ; McNulty, Michelle T. ; Jia, Xiaoyuan ; Gupta, Yask ; Debiec, Hanna ; Luo, Yang ; Nagano, China ; Horinouchi, Tomoko ; Jung, Seulgi ; Colucci, Manuela ; Ahram, Dina F. ; Mitrotti, Adele ; Sinha, Aditi ; Teeninga, Nynke ; Jin, Gina ; Shril, Shirlee ; Caridi, Gianluca ; Bodria, Monica ; Lim, Tze Y. ; Westland, Rik ; Zanoni, Francesca ; Marasa, Maddalena ; Turudic, Daniel ; Giordano, Mario ; Gesualdo, Loreto ; Magistroni, Riccardo ; Pisani, Isabella ; Fiaccadori, Enrico ; Reiterova, Jana ; Maringhini, Silvio ; Morello, William ; Montini, Giovanni ; Weng, Patricia L. ; Scolari, Francesco ; Saraga, Marijan ; Tasic, Velibor ; Santoro, Domenica ; van Wijk, Joanna A.E. ; Milošević, Danko ; Kawai, Yosuke ; Kiryluk, Krzysztof ; Pollak, Martin R. ; Gharavi, Ali ; Lin, Fangmin ; Simœs e Silva, Ana Cristina ; Loos, Ruth J.F. ; Kenny, Eimear E. ; Schreuder, Michiel F. ; Zurowska, Aleksandra ; Dossier, Claire ; Ariceta, Gema ; Drozynska-Duklas, Magdalena ; Hogan, Julien ; Jankauskiene, Augustina ; Hildebrandt, Friedhelm ; Prikhodina, Larisa ; Song, Kyuyoung ; Bagga, Arvind ; Cheong, Hae ; Ghiggeri, Gian Marco ; Vachvanichsanong, Prayong ; Nozu, Kandai ; Lee, Dongwon ; Vivarelli, Marina ; Raychaudhuri, Soumya ; Tokunaga, Katsushi ; Sanna-Cherchi, Simone ; Ronco, Pierre ; Iijima, Kazumoto ; Sampson, Matthew G. / Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. I: Nature Communications. 2023 ; Bind 14, Nr. 1.

Bibtex

@article{e8b09fcffea94a4b9b301e66ab25c765,

title = "Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome",

abstract = "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.",

author = "Alexandra Barry and McNulty, {Michelle T.} and Xiaoyuan Jia and Yask Gupta and Hanna Debiec and Yang Luo and China Nagano and Tomoko Horinouchi and Seulgi Jung and Manuela Colucci and Ahram, {Dina F.} and Adele Mitrotti and Aditi Sinha and Nynke Teeninga and Gina Jin and Shirlee Shril and Gianluca Caridi and Monica Bodria and Lim, {Tze Y.} and Rik Westland and Francesca Zanoni and Maddalena Marasa and Daniel Turudic and Mario Giordano and Loreto Gesualdo and Riccardo Magistroni and Isabella Pisani and Enrico Fiaccadori and Jana Reiterova and Silvio Maringhini and William Morello and Giovanni Montini and Weng, {Patricia L.} and Francesco Scolari and Marijan Saraga and Velibor Tasic and Domenica Santoro and {van Wijk}, {Joanna A.E.} and Danko Milo{\v s}evi{\'c} and Yosuke Kawai and Krzysztof Kiryluk and Pollak, {Martin R.} and Ali Gharavi and Fangmin Lin and {Sim{\oe}s e Silva}, {Ana Cristina} and Loos, {Ruth J.F.} and Kenny, {Eimear E.} and Schreuder, {Michiel F.} and Aleksandra Zurowska and Claire Dossier and Gema Ariceta and Magdalena Drozynska-Duklas and Julien Hogan and Augustina Jankauskiene and Friedhelm Hildebrandt and Larisa Prikhodina and Kyuyoung Song and Arvind Bagga and Hae Cheong and Ghiggeri, {Gian Marco} and Prayong Vachvanichsanong and Kandai Nozu and Dongwon Lee and Marina Vivarelli and Soumya Raychaudhuri and Katsushi Tokunaga and Simone Sanna-Cherchi and Pierre Ronco and Kazumoto Iijima and Sampson, {Matthew G.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41467-023-37985-w",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome

AU - Barry, Alexandra

AU - McNulty, Michelle T.

AU - Jia, Xiaoyuan

AU - Gupta, Yask

AU - Debiec, Hanna

AU - Luo, Yang

AU - Nagano, China

AU - Horinouchi, Tomoko

AU - Jung, Seulgi

AU - Colucci, Manuela

AU - Ahram, Dina F.

AU - Mitrotti, Adele

AU - Sinha, Aditi

AU - Teeninga, Nynke

AU - Jin, Gina

AU - Shril, Shirlee

AU - Caridi, Gianluca

AU - Bodria, Monica

AU - Lim, Tze Y.

AU - Westland, Rik

AU - Zanoni, Francesca

AU - Marasa, Maddalena

AU - Turudic, Daniel

AU - Giordano, Mario

AU - Gesualdo, Loreto

AU - Magistroni, Riccardo

AU - Pisani, Isabella

AU - Fiaccadori, Enrico

AU - Reiterova, Jana

AU - Maringhini, Silvio

AU - Morello, William

AU - Montini, Giovanni

AU - Weng, Patricia L.

AU - Scolari, Francesco

AU - Saraga, Marijan

AU - Tasic, Velibor

AU - Santoro, Domenica

AU - van Wijk, Joanna A.E.

AU - Milošević, Danko

AU - Kawai, Yosuke

AU - Kiryluk, Krzysztof

AU - Pollak, Martin R.

AU - Gharavi, Ali

AU - Lin, Fangmin

AU - Simœs e Silva, Ana Cristina

AU - Loos, Ruth J.F.

AU - Kenny, Eimear E.

AU - Schreuder, Michiel F.

AU - Zurowska, Aleksandra

AU - Dossier, Claire

AU - Ariceta, Gema

AU - Drozynska-Duklas, Magdalena

AU - Hogan, Julien

AU - Jankauskiene, Augustina

AU - Hildebrandt, Friedhelm

AU - Prikhodina, Larisa

AU - Song, Kyuyoung

AU - Bagga, Arvind

AU - Cheong, Hae

AU - Ghiggeri, Gian Marco

AU - Vachvanichsanong, Prayong

AU - Nozu, Kandai

AU - Lee, Dongwon

AU - Vivarelli, Marina

AU - Raychaudhuri, Soumya

AU - Tokunaga, Katsushi

AU - Sanna-Cherchi, Simone

AU - Ronco, Pierre

AU - Iijima, Kazumoto

AU - Sampson, Matthew G.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-37985-w

DO - 10.1038/s41467-023-37985-w

M3 - Journal article

C2 - 37120605

AN - SCOPUS:85156168251

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2481

ER -

ID: 351001802