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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

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机构: [1]Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany [2]Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing,NTNU, Trondheim, Norway [3]Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit, Populat Hlth Sci, Bristol, Avon, England [4]Univ Oslo, Div Med & Lab Sci, Oslo, Norway [5]Univ Med Greifswald, Inst Community Med, Greifswald, Germany [6]DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany [7]Med Univ Bialystok, Dept Populat Med & Lifestyle Dis Prevent, Bialystok, Poland [8]Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany [9]Vanderbilt Univ, Dept Biostat, Med Ctr, Nashville, TN USA [10]Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA [11]Norwegian Univ Sci & Technol, Dept Clin & Mol Med, NTNU, Trondheim, Norway [12]Norwegian Univ Sci & Technol, BioCore Bioinformat Core Facil, Trondheim, Norway [13]Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA [14]Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [15]Univ Freiburg, Inst Genet Epidemiol, Dept Data Driven Med, Fac Med, Freiburg, Germany [16]Univ Freiburg, Med Ctr, Freiburg, Germany [17]Merck & Co Inc, Genet, Kenilworth, NJ USA [18]Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA [19]Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands [20]Natl Res Council Italy, Inst Biomed Technol, Milan, Italy [21]Bio4Dreams Business Nursery Life Sci, Milan, Italy [22]Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore [23]Natl Univ Hlth Syst, Singapore, Singapore [24]GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA [25]Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany [26]Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany [27]Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA [28]IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy [29]Univ Freiburg, Dept Med 4, Renal Div, Fac Med, Freiburg, Germany [30]Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [31]Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany [32]CNR, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy [33]Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy [34]Univ Trento, Dept Cellular Computat & Integrat Biol CIBIO, Trento, Italy [35]Ludwig Maximilians Univ Munchen, Stat Consulting Unit StaBLab, Dept Stat, Munich, Germany [36]Imperial Coll London, Fac Med, MRC Ctr Environm & Hlth, Sch Publ Hlth,Dept Epidemiol & Biostat, London, England [37]Imperial Coll London, Dementia Res Inst, London, England [38]NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA [39]Univ Maryland, Sch Med, Baltimore, MD 21201 USA [40]Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy [41]Leiden Univ, Dept Internal Med, Sect Nephrol, Med Ctr, Leiden, Netherlands [42]NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA [43]Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland [44]Univ Lille, European Genom Inst Diabet EGID, Inst Pasteur Lille, CNRS UMR 8199, Lille, France [45]Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands [46]Med Univ Graz, Dept Internal Med, Div Nephrol, Graz, Austria [47]Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany [48]Heart Ctr Leipzig, Leipzig, Germany [49]Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia [50]Univ Liverpool, Dept Hlth Data Sci, Liverpool, Merseyside, England [51]Univ Oxford, Wellcome Ctr Human Genet, Oxford OX3 7BN, England [52]Univ Manchester, Ctr Genet & Genom Versus Arthrit, Ctr Musculoskeletal Res, Manchester, Lancs, England [53]Univ Leipzig, Med Ctr, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany [54]Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany [55]German Ctr Diabet Res DZD, Neuherberg, Germany [56]Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Epidemiol, Munich, Germany [57]Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany [58]Univ Leipzig, Ctr Pediat Res, Leipzig, Germany [59]Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Canc, Edinburgh, Midlothian, Scotland [60]Wake Forest Sch Med, Sect Nephrol, Internal Med, Winston Salem, NC 27101 USA [61]Geneva Univ Hosp, Med Dept, Serv Nephrol & Hypertens, Geneva, Switzerland [62]German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany [63]Heidelberg Univ, Network Aging Res, Heidelberg, Germany [64]Trondheim Reg & Univ Hosp, Clin Med, St Olavs Hosp, N-7030 Trondheim, Norway [65]Norwegian Univ Sci & Technol, HUNT Res Ctr, Dept Publ Hlth & Nursing, NTNU, N-7600 Levanger, Norway [66]Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany [67]Kliniken Sudostbayern, Dept Nephrol & Rheumatol, Traunstein, Germany [68]Trondheim Reg & Univ Hosp, Clin Med, Dept Endocrinol, St Olavs Hosp, Trondheim, Norway [69]Univ Dundee, Ninewells Hosp & Med Sch, Div Populat Hlth & Genom, Dundee, Scotland [70]Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands [71]Univ Michigan, Dept Biostat, Sch Publ Hlth, Ann Arbor, MI 48109 USA [72]Univ Michigan, Ctr Stat Genet, Sch Publ Hlth, Ann Arbor, MI 48109 USA [73]Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA [74]Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA [75]Univ Washington, Dept Hlth Syst & Populat Hlth, Seattle, WA 98195 USA [76]Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA [77]Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC 27101 USA [78]Univ Edinburgh, Inst Genet & Canc, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland [79]Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA [80]Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA [81]Vanderbilt Univ, Vanderbilt Ctr Kidney Dis & Integrated Program Ac, Div Nephrol & Hypertens, Med Ctr, Nashville, TN USA [82]Vanderbilt Precis Nephrol Program Nashville, Nashville, TN USA [83]Univ Oxford, Nuffield Dept Med, Oxford, England [84]Broad Inst Harvard & MIT, Cambridge, MA USA [85]Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford OX3 7LF, England [86]Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore [87]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Wuhan, Peoples R China [88]Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore [89]Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore [90]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore [91]Natl Univ Hlth Syst, Khoo Teck Puat Natl Univ Childrens Med Inst, Singapore, Singapore [92]IRCCS San Raffaele Sci Inst, Nephrol & Dialysis Unit, Genom Renal Dis & Hypertens Unit, Milan, Italy [93]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore [94]Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany [95]Vanderbilt Univ, Dept Biomed Informat, Med Ctr, Nashville, TN USA [96]Lund Univ, Dept Clincial Sci Malmo, Malmo, Sweden [97]Univ Michigan, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48109 USA [98]Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA [99]Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA [100]Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA [101]Harvard Med Sch, Boston, MA 02115 USA [102]Amgen Inc, deCODE Genet, Reykjavik, Iceland [103]Univ Iceland, Iceland Sch Engn & Nat Sci, Reykjavik, Iceland [104]IRCCS Neuromed, Pozzilli, Italy [105]San Raffaele Res Inst, Milan, Italy [106]Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany [107]Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland [108]Uppsala Univ, Ctr Res Eth & Bioeth, Dept Publ Hlth & Caring Sci, Uppsala, Sweden [109]Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands [110]Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands [111]Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA [112]Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria [113]Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria [114]Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA [115]Fdn IRCCS Ist Neurol Carlo Besta, Neuroalgol Unit, Milan, Italy [116]Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA [117]Hasso Plattner Inst, Digital Hlth Ctr, Potsdam, Germany [118]Univ Potsdam, Potsdam, Germany [119]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore [120]Duke NUS Med Sch, Singapore, Singapore [121]ePhood SRL, ePhood Sci Unit, Milan, Italy [122]Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands [123]Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands [124]Geneva Univ Hosp, Cardiol, Geneva, Switzerland [125]Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland [126]Univ Lausanne, Lausanne, Switzerland [127]Natl Res Council Italy, Inst Mol Genet Luigi Luca Cavalli Sforza, Pavia, Italy [128]Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland [129]Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA [130]Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany [131]Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia [132]Univ Edinburgh, Ctr Global Hlth, Usher Inst, Edinburgh, Midlothian, Scotland [133]Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand [134]Univ Auckland, Auckland, New Zealand [135]Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA [136]Univ 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Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing Key Lab Ophthalmol & Visual Sci, Beijing, Peoples R China [149]Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany [150]Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden [151]Dalarna Univ, Sch Hlth & Social Studies, Stockholm, Sweden [152]Univ Eastern Finland, Kuopio, Finland [153]Kuopio Univ Hosp, Kuopio, Finland [154]Iceland Heart Assoc, Kopavogur, Iceland [155]Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland [156]CHUM, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada [157]CRCHUM, Montreal, PQ, Canada [158]Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore [159]QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia [160]Harvard Med Sch, Dept Internal Med, Boston, MA 02115 USA [161]VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA USA [162]Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany [163]Inst Mol & Clin Ophthalmol, Basel, Switzerland [164]Privatpraxis Prof Jonas & Dr Panda Jonas, Heidelberg, Germany [165]Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA [166]Univ Southern Denmark, Danish Aging Res Ctr, Odense C, Denmark [167]Charite, Intens Care Med, Berlin, Germany [168]Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Nephrol & Hypertens, Erlangen, Germany [169]Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany [170]Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA [171]Univ Washington, Dept Biostat, Seattle, WA 98195 USA [172]Geisinger Res, Biomed & Translat Informat Inst, Rockville, MD USA [173]Geisinger, Dept Nephrol, Danville, PA USA [174]Tampere Univ Hosp, Heart Ctr, Dept Cardiol, Tampere, Finland [175]Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Cardiol, Tampere, Finland [176]Univ Tokyo, Grad Sch Frontier Sci, Lab Clin Genome Sequencing, Tokyo, Japan [177]Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany [178]Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany [179]Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat IMBEI, Mainz, Germany [180]Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden [181]Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden [182]Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden [183]Atlanta VA Hlth Care Syst, Decatur, GA USA [184]Emory Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Atlanta, GA USA [185]NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA [186]Fimlab Labs, Dept Clin Chem, Tampere, Finland [187]Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland [188]Univ Colorado Denver, Div Biomed Informat & Personalized Med, Sch Med, Anschutz Med Campus, Aurora, CO USA [189]Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands [190]Max Planck Inst Psychiat, Munich, Germany [191]SYNLAB MVZ Humangenet Mannheim, Mannheim, Germany [192]Natl Res Council Italy, Inst Genet & Biomed Res, Cagliari, Italy [193]Finnish Inst Hlth & Welf, Helsinki, Finland [194]Univ Helsinki, Fac Med, Res Program Clin & Mol Metab, Helsinki, Finland [195]Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands [196]GlaxoSmithKline, Target Sci Genet, Albuquerque, NM USA [197]RIKEN Ctr Integrat Med Sci IMS, Lab Stat Anal, Yokohama, Kanagawa, Japan [198]Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA [199]Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan [200]Tohoku Univ, Dept Ophthalmol, Grad Sch Med, Sendai, Miyagi, Japan [201]Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany [202]DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany [203]Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA [204]TIMI Study Grp, Boston, MA USA [205]RIKEN Ctr Integrat Med Sci IMS, Yokohama, Kanagawa, Japan [206]Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland [207]Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere, Finland [208]NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA [209]Data Tecn Int, Glen Echo, MD USA [210]Finnish Inst Hlth & Welf, Dept Publ Hlth & Welf, Helsinki, Finland [211]Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Sch Med, Brownsville, TX USA [212]Univ Texas Rio Grande Valley, Dept Human Genet, Sch Med, Brownsville, TX USA [213]Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad, Razavi Khorasan, Iran [214]Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, CH-1010 Lausanne, Switzerland [215]Geisinger Hlth, Dept Populat Hlth Sci, 100 N Acad Ave, Danville, PA USA [216]Wake Forest Sch Med, Biochem, Winston Salem, NC 27101 USA [217]Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Med Ctr, New York, NY USA [218]Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands [219]Tampere Univ, Fac Med & Hlth Technol, Tampere Ctr Skills Training & Simulat, Tampere, Finland [220]Univ Washington, Div Nephrol, Seattle, WA 98195 USA [221]Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA [222]Univ Zurich, Inst Physiol, Zurich, Switzerland [223]Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland [224]Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland [225]Univ Turku, Ctr Populat Hlth Res, Turku, Finland [226]Turku Univ Hosp, Turku, Finland [227]Univ Split, Fac Med, Split, Croatia [228]Algebra Univ Coll, Ilica 242, Zagreb, Croatia [229]Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [230]Imperial Coll London, Imperial Coll NIHR Biomed Res Ctr, London, England [231]Hlth Data Res UK, London, England [232]Medpharmgene, Montreal, PQ, Canada [233]Soder Sjukhuset, Dept Clin Sci & Educ, Karolinska Inst, Stockholm, Sweden [234]Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden [235]Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Leipzig, Germany [236]Steno Diabet Ctr Copenhagen, Herlev, Denmark [237]Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark [238]Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands [239]Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany [240]Vanderbilt Univ, Vanderbilt Genet Inst, Med Ctr, Nashville, TN USA [241]Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands [242]Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland [243]Swiss Inst Bioinformat, Lausanne, Switzerland [244]George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA [245]Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA [246]Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Dept Hlth & Med Sci, Copenhagen, Denmark [247]Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland [248]Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany [249]Geisinger Res, Biomed & Translat Informat Inst, Danville, PA USA [250]NHLBIs Framingham Heart Study, Framingham, MA USA [251]NHLBI, Ctr Populat Studies, Framingham, MA USA [252]Trondheim Reg & Univ Hosp, Dept Nephrol, St Olavs Hosp, Trondheim, Norway [253]Khoo Teck Puat Hosp, Diabet Ctr, Singapore, Singapore [254]Univ Copenhagen, Fac Sci, Bioinformat Ctr, Dept Biol, Copenhagen, Denmark [255]Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany [256]Tech Univ Munich, Inst Human Genet, Munich, Germany [257]Leiden Univ, Einthoven Lab Expt Vasc Res, Med Ctr, Leiden, Netherlands [258]Broad Inst, Program Med & Populat Genet, Cambridge, MA USA [259]Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany [260]Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, Uppsala, Sweden [261]Chinese Natl Human Genome Ctr, Dept Genet, Shanghai MOST Key Lab Hlth & Dis Genom, Shanghai, Peoples R China [262]Shanghai Ind Technol Inst, Shanghai, Peoples R China [263]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China [264]Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany [265]Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria [266]Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany [267]Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany [268]Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany [269]Hebrew Univ Jerusalem, Sch Publ Hlth & Community Med, Jerusalem, Israel [270]Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Lab Complex Trait Genom, Tokyo, Japan [271]RIKEN Ctr Integrat Med Sci IMS, Lab Syst Genet, Osaka, Japan [272]Osaka Univ, Dept Stat Genet, Grad Sch Med, Osaka, Japan [273]Massachusetts Gen Hosp, Boston, MA 02114 USA [274]Med Univ Innsbruck, Inst Genet Epidemiol, Dept Genet & Pharmacol, Innsbruck, Austria
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A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease. Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.

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出版当年[2021]版:
大类 | 2 区 生物学
小类 | 1 区 生物学
最新[2023]版:
大类 | 1 区 生物学
小类 | 1 区 生物学
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出版当年[2020]版:
Q1 BIOLOGY
最新[2023]版:
Q1 BIOLOGY

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第一作者机构: [1]Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany
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