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- Beijer, KristinaUppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR) (author)
In search of causal pathways in diabetes : a study using proteomics and genotyping data from a cross-sectional study
- Article/chapterEnglish2019
Publisher, publication year, extent ...
- 2019-08-24
- SPRINGER,2019
- electronicrdacarrier
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- LIBRIS-ID:oai:DiVA.org:uu-396951
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396951URI
- https://doi.org/10.1007/s00125-019-4960-8DOI
- http://kipublications.ki.se/Default.aspx?queryparsed=id:142158391URI
- https://urn.kb.se/resolve?urn=urn:nbn:se:du-30694URI
Supplementary language notes
- Language:English
- Summary in:English
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- Aims/hypothesis: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal.Methods: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of >= 7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study.Results: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, alpha-l-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes.Conclusions/interpretation: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
- Diabetes
- Genotyping
- Mendelian randomisation
- Proteomics
- Type 2 diabetes
- Hälsa och välfärd
Added entries (persons, corporate bodies, meetings, titles ...)
- Nowak, ChristophKarolinska Institutet (author)
- Sundström, Johan,Professor,1971-Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)johasund (author)
- Ärnlöv, JohanHögskolan Dalarna,Karolinska Institutet,Medicinsk vetenskap(Swepub:du)jan (author)
- Fall, Tove,1979-Uppsala universitet,Molekylär epidemiologi(Swepub:uu)tovfa878 (author)
- Lind, LarsUppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)larslind (author)
- Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)
Related titles
- In:Diabetologia: SPRINGER62:11, s. 1998-20060012-186X1432-0428
Internet link
- https://doi.org/10.1007/s00125-019-4960-8Fulltext
- https://uu.diva-portal.org/smash/get/diva2:1370570/FULLTEXT01.pdffulltext:print
- https://link.springer.com/content/pdf/10.1007/s00125-019-4960-8.pdf
- https://du.diva-portal.org/smash/get/diva2:1351939/FULLTEXT01.pdffulltext:print
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396951
- https://doi.org/10.1007/s00125-019-4960-8
- http://kipublications.ki.se/Default.aspx?queryparsed=id:142158391
- https://urn.kb.se/resolve?urn=urn:nbn:se:du-30694
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