{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:12:53Z","timestamp":1779804773367,"version":"3.53.1"},"reference-count":30,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"unspecified","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0052457"],"award-info":[{"award-number":["NNF18OC0052457"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2026,5,2]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is a global health and economic burden, particularly among individuals with type 2 diabetes (T2D). According to Kidney Disease: Improving Global Outcomes guidelines, key CKD indicators include urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Although independent genetic loci for these traits have been reported, their shared genetic architecture remains insufficiently understood. We hypothesized that there are shared genetic markers of kidney function (eGFR) and albuminuria generally, but also specific to the T2D population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a cross-sectional observational study including 432\u2009451 UK Biobank participants of primarily European descent (94%), with a subgroup of 16\u2009265 with T2D after data quality control. We examined whether 423 single-nucleotide polymorphisms previously associated with eGFR in a large genome-wide association study meta-analysis were associated with (a) eGFR estimated using the 2021 race-free CKD-Epidemiology Collaboration creatinine equation (eGFR\n                      <jats:sub>2021<\/jats:sub>\n                      ) and (b) UACR. Multiple linear regression models were adjusted for systolic blood pressure, age, sex, and the first 10 genetic principal components to account for population stratification. Analyses were performed using Python and R. Bonferroni correction (BC) was performed. For the T2D subgroup, the models were additionally adjusted for body mass index and glycated hemoglobin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the overall population, 422 loci were nominally associated with eGFR\n                      <jats:sub>2021<\/jats:sub>\n                      , of which 75 were nominally associated with UACR (p\u22640.05); 12 remained significant after BC (\n                      <jats:italic>\n                        P\n                        <jats:sub>b<\/jats:sub>\n                      <\/jats:italic>\n                      \u2264\n                      <jats:inline-formula>\n                        <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                          <m:mn>1.18<\/m:mn>\n                          <m:mo>\u00d7<\/m:mo>\n                          <m:msup>\n                            <m:mrow>\n                              <m:mn>10<\/m:mn>\n                            <\/m:mrow>\n                            <m:mrow>\n                              <m:mo>-<\/m:mo>\n                              <m:mn>4<\/m:mn>\n                            <\/m:mrow>\n                          <\/m:msup>\n                        <\/m:math>\n                      <\/jats:inline-formula>\n                      ). In the T2D subgroup, 76 loci nominally associated with eGFR\n                      <jats:sub>2021<\/jats:sub>\n                      , six also associated nominally with UACR (p\u22640.05), and one remained significant after BC (\n                      <jats:italic>\n                        P\n                        <jats:sub>b<\/jats:sub>\n                      <\/jats:italic>\n                      \u2264\n                      <jats:inline-formula>\n                        <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                          <m:mn>6.58<\/m:mn>\n                          <m:mo>\u00d7<\/m:mo>\n                          <m:msup>\n                            <m:mrow>\n                              <m:mn>10<\/m:mn>\n                            <\/m:mrow>\n                            <m:mrow>\n                              <m:mo>-<\/m:mo>\n                              <m:mn>4<\/m:mn>\n                            <\/m:mrow>\n                          <\/m:msup>\n                        <\/m:math>\n                      <\/jats:inline-formula>\n                      ). Two pleiotropic loci (\n                      <jats:italic>GSTA2, USP2-AS1<\/jats:italic>\n                      ) suggested diabetes-specific effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies several shared genetic loci underlying eGFR and UACR in both general and T2D European populations. These findings highlight common pathobiological pathways between albuminuria and reduced kidney function and provide a genetic map that may inform future CKD risk stratification and towards the development of therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjdrc-2025-005863","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:45:13Z","timestamp":1779803113000},"page":"e005863","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping shared genetic determinants of eGFR and albuminuria with a focus on type 2 diabetes: a large-scale European study"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7578-9592","authenticated-orcid":false,"given":"Cilia","family":"Naaman","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Persson","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"K\u00fcmler","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-8951","authenticated-orcid":false,"given":"Simone","family":"Theilade","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Chertow","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Departments of Medicine, Epidemiology and Population Health, and Health Policy, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-4294","authenticated-orcid":false,"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-0352","authenticated-orcid":false,"given":"Tine","family":"Hansen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-3354","authenticated-orcid":false,"given":"Tarunveer S","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Science and Environment, Roskilde University, Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"2026052606450585000_14.3.e005863.1","unstructured":"Prevalence and disease burden of chronic kidney disease. 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