| Title |
Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes
|
|---|---|
| Published in |
Diabetologia, February 2018
|
| DOI | 10.1007/s00125-018-4555-9 |
| Pubmed ID | |
| Authors |
Delnaz Roshandel, Rose Gubitosi-Klug, Shelley B. Bull, Angelo J. Canty, Marcus G. Pezzolesi, George L. King, Hillary A. Keenan, Janet K. Snell-Bergeon, David M. Maahs, Ronald Klein, Barbara E. K. Klein, Trevor J. Orchard, Tina Costacou, Michael N. Weedon, DCCT/EDIC Research Group, Richard A. Oram, Andrew D. Paterson |
| Abstract |
The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS). We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n = 1303), fasting (n = 2019) and random (n = 1497) C-peptide levels. In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p = 4.13 × 10-8), meeting the genome-wide significance threshold (p < 5 × 10-8). In the same meta-GWAS, a locus in the MHC region (rs9260151) was close to the genome-wide significance threshold (Chr6:29911030, C>T, MAF 0.07-0.10, p = 8.43 × 10-8). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (β [SE] = - 0.39 [0.07], p = 9.72 × 10-8). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n = 258) with annual repeated measures for up to 6 years (p = 0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p = 3.49 × 10-8). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes. We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C-peptide, suggesting partly non-overlapping mechanisms for the development and progression of type 1 diabetes. These associations need to be validated in independent populations. Further investigations could provide insights into mechanisms of beta cell loss and opportunities to preserve beta cell function. |
X Demographics
The data shown below were collected from the profiles of 10 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 Kingdom | 4 | 40% |
| Germany | 1 | 10% |
| France | 1 | 10% |
| United States | 1 | 10% |
| India | 1 | 10% |
| Unknown | 2 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 50% |
| Scientists | 4 | 40% |
| Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 44 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 16% |
| Researcher | 6 | 14% |
| Student > Postgraduate | 5 | 11% |
| Student > Bachelor | 4 | 9% |
| Student > Master | 4 | 9% |
| Other | 7 | 16% |
| Unknown | 11 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 18% |
| Biochemistry, Genetics and Molecular Biology | 6 | 14% |
| Nursing and Health Professions | 4 | 9% |
| Computer Science | 4 | 9% |
| Agricultural and Biological Sciences | 3 | 7% |
| Other | 8 | 18% |
| Unknown | 11 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 04 April 2018.
All research outputs
#4,754,345
of 23,577,654 outputs
Outputs from Diabetologia
#2,017
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Outputs of similar age
#104,108
of 440,028 outputs
Outputs of similar age from Diabetologia
#44
of 68 outputs
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