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A novel rare CUBN v...
A novel rare CUBN variant and three additional genes identified in Europeans with and without diabetes : results from an exome-wide association study of albuminuria
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- Ahluwalia, Tarunveer S. (författare)
- Herlev Hospital,University of Copenhagen,Steno Diabetes Center Copenhagen
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- Schulz, Christina Alexandra (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Waage, Johannes (författare)
- Herlev Hospital,University of Copenhagen
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- Skaaby, Tea (författare)
- Frederiksberg Hospital
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- Sandholm, Niina (författare)
- Helsinki University Central Hospital,Folkhälsan Research Center,University of Helsinki
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- van Zuydam, Natalie (författare)
- University of Oxford
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- Charmet, Romain (författare)
- Paris-Sorbonne University
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- Bork-Jensen, Jette (författare)
- University of Copenhagen
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- Almgren, Peter (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Thuesen, Betina H. (författare)
- Frederiksberg Hospital
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- Bedin, Mathilda (författare)
- Paris Descartes University
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- Brandslund, Ivan (författare)
- Lillebaelt Hospital
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- Christensen, Cramer K. (författare)
- Lillebaelt Hospital
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- Linneberg, Allan (författare)
- Frederiksberg Hospital
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- Ahlqvist, Emma (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Groop, Per Henrik (författare)
- Helsinki University Central Hospital,Folkhälsan Research Center,Monash University,University of Helsinki
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- Hadjadj, Samy (författare)
- Nantes University Hospital
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- Tregouet, David Alexandre (författare)
- Paris-Sorbonne University
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- Jørgensen, Marit E. (författare)
- University of Southern Denmark,Steno Diabetes Center Copenhagen
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- Grarup, Niels (författare)
- University of Copenhagen
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- Pedersen, Oluf (författare)
- University of Copenhagen
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- Simons, Matias (författare)
- Paris Descartes University
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Institute for Molecular Medicine Finland (FIMM),University of Helsinki
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- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- McCarthy, Mark I. (författare)
- University of Oxford
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- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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- Rossing, Peter (författare)
- Steno Diabetes Center Copenhagen,University of Copenhagen
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- Kilpeläinen, Tuomas O. (författare)
- University of Copenhagen
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- Hansen, Torben (författare)
- University of Copenhagen,University of Southern Denmark
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(creator_code:org_t)
- 2018-12-13
- 2019
- Engelska.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:2, s. 292-305
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http://dx.doi.org/10... (free)
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https://link.springe...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims/hypothesis: Identifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants. Methods: We performed an exome-wide association study to identify coding variants in a two-stage (discovery and replication) approach. Data from 33,985 individuals of European ancestry (15,872 with and 18,113 without diabetes) and 2605 Greenlanders were included. Results: We identified a rare (minor allele frequency [MAF]: 0.8%) missense (A1690V) variant in CUBN (rs141640975, β = 0.27, p = 1.3 × 10−11) associated with albuminuria as a continuous measure in the combined European meta-analysis. The presence of each rare allele of the variant was associated with a 6.4% increase in albuminuria. The rare CUBN variant had an effect that was three times stronger in individuals with type 2 diabetes compared with those without (pinteraction = 7.0 × 10−4, β with diabetes = 0.69, β without diabetes = 0.20) in the discovery meta-analysis. Gene-aggregate tests based on rare and common variants identified three additional genes associated with albuminuria (HES1, CDC73 and GRM5) after multiple testing correction (pBonferroni < 2.7 × 10−6). Conclusions/interpretation: The current study identifies a rare coding variant in the CUBN locus and other potential genes associated with albuminuria in individuals with and without diabetes. These genes have been implicated in renal and cardiovascular dysfunction. The findings provide new insights into the genetic architecture of albuminuria and highlight target genes and pathways for the prevention of diabetes-related kidney disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Albuminuria
- Diabetes
- DKD
- Exome chip
- Genetics
- Genome-wide association study
- GWAS
- Kidney disease
- Rare variant
- SKAT
- Type 2 diabetes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Ahluwalia, Tarun ...
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Schulz, Christin ...
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Waage, Johannes
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Skaaby, Tea
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Sandholm, Niina
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van Zuydam, Nata ...
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visa fler...
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Charmet, Romain
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Bork-Jensen, Jet ...
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Almgren, Peter
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Thuesen, Betina ...
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Bedin, Mathilda
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Brandslund, Ivan
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Christensen, Cra ...
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Linneberg, Allan
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Ahlqvist, Emma
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Groop, Per Henri ...
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Hadjadj, Samy
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Tregouet, David ...
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Jørgensen, Marit ...
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Grarup, Niels
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Pedersen, Oluf
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Simons, Matias
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Groop, Leif
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Orho-Melander, M ...
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McCarthy, Mark I ...
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Melander, Olle
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Rossing, Peter
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Kilpeläinen, Tuo ...
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Hansen, Torben
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Diabetologia
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