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DOI 10.1038/s41467-018-07867-7

Медицинская библиотека · Nature communications · 2019

Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

Morris Andrew P, Le Thu H, Wu Haojia, Akbarov Artur, van der Most Peter J, Hemani Gibran, Smith George Davey, Mahajan Anubha, Gaulton Kyle J, Nadkarni Girish N, Valladares-Salgado Adan, Wacher-Rodarte Niels, Mychaleckyj Josyf C, Dueker Nicole D, Guo Xiuqing, Hai Yang, Haessler Jeffrey, Kamatani Yoichiro, Stilp Adrienne M, Zhu Gu, Cook James P, Ärnlöv Johan, Blanton Susan H, de Borst Martin H, Bottinger Erwin P, Buchanan Thomas A, Cechova Sylvia, Charchar Fadi J, Chu Pei-Lun, Damman Jeffrey, Eales James, Gharavi Ali G, Giedraitis Vilmantas, Heath Andrew C, Ipp Eli, Kiryluk Krzysztof, Kramer Holly J, Kubo Michiaki, Larsson Anders, Lindgren Cecilia M, Lu Yingchang, Madden Pamela A F, Montgomery Grant W, Papanicolaou George J, Raffel Leslie J, Sacco Ralph L, Sanchez Elena, Stark Holger, Sundstrom Johan, Taylor Kent D, Xiang Anny H, Zivkovic Aleksandra, Lind Lars, Ingelsson Erik, Martin Nicholas G, Whitfield John B, Cai Jianwen, Laurie Cathy C, Okada Yukinori, Matsuda Koichi, Kooperberg Charles, Chen Yii-Der Ida, Rundek Tatjana, Rich Stephen S, Loos Ruth J F, Parra Esteban J, Cruz Miguel, Rotter Jerome I, Snieder Harold, Tomaszewski Maciej, Humphreys Benjamin D, Franceschini Nora

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

Для цитирования: Morris Andrew P, Le Thu H, Wu Haojia, Akbarov Artur, van der Most Peter J, Hemani Gibran, Smith George Davey, Mahajan Anubha, Gaulton Kyle J, Nadkarni Girish N, Valladares-Salgado Adan, Wacher-Rodarte Niels, Mychaleckyj Josyf C, Dueker Nicole D, Guo Xiuqing, Hai Yang, Haessler Jeffrey, Kamatani Yoichiro, Stilp Adrienne M, Zhu Gu, Cook James P, Ärnlöv Johan, Blanton Susan H, de Borst Martin H, Bottinger Erwin P, Buchanan Thomas A, Cechova Sylvia, Charchar Fadi J, Chu Pei-Lun, Damman Jeffrey, Eales James, Gharavi Ali G, Giedraitis Vilmantas, Heath Andrew C, Ipp Eli, Kiryluk Krzysztof, Kramer Holly J, Kubo Michiaki, Larsson Anders, Lindgren Cecilia M, Lu Yingchang, Madden Pamela A F, Montgomery Grant W, Papanicolaou George J, Raffel Leslie J, Sacco Ralph L, Sanchez Elena, Stark Holger, Sundstrom Johan, Taylor Kent D, Xiang Anny H, Zivkovic Aleksandra, Lind Lars, Ingelsson Erik, Martin Nicholas G, Whitfield John B, Cai Jianwen, Laurie Cathy C, Okada Yukinori, Matsuda Koichi, Kooperberg Charles, Chen Yii-Der Ida, Rundek Tatjana, Rich Stephen S, Loos Ruth J F, Parra Esteban J, Cruz Miguel, Rotter Jerome I, Snieder Harold, Tomaszewski Maciej, Humphreys Benjamin D, Franceschini Nora. Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.. Nature communications. 2019. DOI: 10.1038/s41467-018-07867-7.

Предметные рубрики MeSH

AdultAgedBlood PressureEthnicityFemaleGenetic LociGenome-Wide Association StudyGlomerular Filtration RateHistone CodeHistonesHumansHypertensionKidneyKidney CalculiMaleMiddle AgedPolymorphism, Single NucleotideRenal Insufficiency, Chronic
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