| Title |
Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes
|
|---|---|
| Published in |
Diabetologia, July 2016
|
| DOI | 10.1007/s00125-016-4041-1 |
| Pubmed ID | |
| Authors |
Tove Fall, Samira Salihovic, Stefan Brandmaier, Christoph Nowak, Andrea Ganna, Stefan Gustafsson, Corey D. Broeckling, Jessica E. Prenni, Gabi Kastenmüller, Annette Peters, Patrik K. Magnusson, Rui Wang-Sattler, Vilmantas Giedraitis, Christian Berne, Christian Gieger, Nancy L. Pedersen, Erik Ingelsson, Lars Lind |
| Abstract |
Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction. In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855). Assessment of the association of metabolite-regulating genetic variants with type 2 diabetes was done using data from a meta-analysis of genome-wide association studies. Out of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes. We found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes. Metabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS). |
X Demographics
The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 8 | 36% |
| Finland | 3 | 14% |
| United Kingdom | 2 | 9% |
| Spain | 1 | 5% |
| Sweden | 1 | 5% |
| India | 1 | 5% |
| Brazil | 1 | 5% |
| Unknown | 5 | 23% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 12 | 55% |
| Members of the public | 8 | 36% |
| Practitioners (doctors, other healthcare professionals) | 1 | 5% |
| Science communicators (journalists, bloggers, editors) | 1 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 126 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 2 | 2% |
| Germany | 1 | <1% |
| Korea, Republic of | 1 | <1% |
| Netherlands | 1 | <1% |
| United Kingdom | 1 | <1% |
| Austria | 1 | <1% |
| Unknown | 119 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 27 | 21% |
| Researcher | 21 | 17% |
| Student > Bachelor | 14 | 11% |
| Student > Master | 11 | 9% |
| Other | 6 | 5% |
| Other | 24 | 19% |
| Unknown | 23 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 20 | 16% |
| Agricultural and Biological Sciences | 17 | 13% |
| Biochemistry, Genetics and Molecular Biology | 16 | 13% |
| Chemistry | 10 | 8% |
| Nursing and Health Professions | 4 | 3% |
| Other | 26 | 21% |
| Unknown | 33 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 October 2016.
All research outputs
#2,657,032
of 25,732,188 outputs
Outputs from Diabetologia
#1,329
of 5,376 outputs
Outputs of similar age
#46,268
of 371,386 outputs
Outputs of similar age from Diabetologia
#26
of 77 outputs
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