Genome-wide discovery for diabetes-dependent triglycerides-associated loci.
<h4>Purpose</h4>We aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). We conducted a genome-wide association study (GWAS) in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels.<h4>Methods</h4...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0275934 |
| _version_ | 1797753800691286016 |
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| author | Margaret Sunitha Selvaraj Kaavya Paruchuri Sara Haidermota Rachel Bernardo Stephen S Rich Gina M Peloso Pradeep Natarajan |
| author_facet | Margaret Sunitha Selvaraj Kaavya Paruchuri Sara Haidermota Rachel Bernardo Stephen S Rich Gina M Peloso Pradeep Natarajan |
| author_sort | Margaret Sunitha Selvaraj |
| collection | DOAJ |
| description | <h4>Purpose</h4>We aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). We conducted a genome-wide association study (GWAS) in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels.<h4>Methods</h4>We stratified the cohort based on T2D status and conducted association analyses of TG levels for genetic variants with minor allele count (MAC) at least 20 in each stratum. Effect differences of genetic variants by T2D status were determined by Cochran's Q-test and we validated the significantly associated variants in the Mass General Brigham Biobank (MGBB).<h4>Results</h4>Among 21,176 T2D and 402,944 non-T2D samples from UKB, stratified GWAS identified 19 and 315 genomic risk loci significantly associated with TG levels, respectively. Only chr6p21.32 exhibited genome-wide significant heterogeneity (I2 = 98.4%; pheterogeneity = 2.1x10-15), with log(TG) effect estimates of -0.066 (95%CI: -0.082, -0.050) and 0.002 (95%CI: -0.002, 0.006) for T2D and non-T2D, respectively. The lead variant rs9274619:A (allele frequency 0.095) is located 2Kb upstream of the HLA-DQB1 gene, between HLA-DQB1 and HLA-DQA2 genes. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (pheterogeneity = 9.5x10-3). Phenome-wide interaction association analyses showed that the lead variant was strongly associated with a concomitant diagnosis of type 1 diabetes (T1D) as well as diabetes-associated complications.<h4>Conclusion</h4>In conclusion, we identified an intergenic variant near HLA-DQB1/DQA2 significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D. |
| first_indexed | 2024-03-12T17:24:13Z |
| format | Article |
| id | doaj.art-328aa3921cc9460f9521afeb0c900dc1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-12T17:24:13Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-328aa3921cc9460f9521afeb0c900dc12023-08-05T05:31:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710e027593410.1371/journal.pone.0275934Genome-wide discovery for diabetes-dependent triglycerides-associated loci.Margaret Sunitha SelvarajKaavya ParuchuriSara HaidermotaRachel BernardoStephen S RichGina M PelosoPradeep Natarajan<h4>Purpose</h4>We aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). We conducted a genome-wide association study (GWAS) in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels.<h4>Methods</h4>We stratified the cohort based on T2D status and conducted association analyses of TG levels for genetic variants with minor allele count (MAC) at least 20 in each stratum. Effect differences of genetic variants by T2D status were determined by Cochran's Q-test and we validated the significantly associated variants in the Mass General Brigham Biobank (MGBB).<h4>Results</h4>Among 21,176 T2D and 402,944 non-T2D samples from UKB, stratified GWAS identified 19 and 315 genomic risk loci significantly associated with TG levels, respectively. Only chr6p21.32 exhibited genome-wide significant heterogeneity (I2 = 98.4%; pheterogeneity = 2.1x10-15), with log(TG) effect estimates of -0.066 (95%CI: -0.082, -0.050) and 0.002 (95%CI: -0.002, 0.006) for T2D and non-T2D, respectively. The lead variant rs9274619:A (allele frequency 0.095) is located 2Kb upstream of the HLA-DQB1 gene, between HLA-DQB1 and HLA-DQA2 genes. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (pheterogeneity = 9.5x10-3). Phenome-wide interaction association analyses showed that the lead variant was strongly associated with a concomitant diagnosis of type 1 diabetes (T1D) as well as diabetes-associated complications.<h4>Conclusion</h4>In conclusion, we identified an intergenic variant near HLA-DQB1/DQA2 significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D.https://doi.org/10.1371/journal.pone.0275934 |
| spellingShingle | Margaret Sunitha Selvaraj Kaavya Paruchuri Sara Haidermota Rachel Bernardo Stephen S Rich Gina M Peloso Pradeep Natarajan Genome-wide discovery for diabetes-dependent triglycerides-associated loci. PLoS ONE |
| title | Genome-wide discovery for diabetes-dependent triglycerides-associated loci. |
| title_full | Genome-wide discovery for diabetes-dependent triglycerides-associated loci. |
| title_fullStr | Genome-wide discovery for diabetes-dependent triglycerides-associated loci. |
| title_full_unstemmed | Genome-wide discovery for diabetes-dependent triglycerides-associated loci. |
| title_short | Genome-wide discovery for diabetes-dependent triglycerides-associated loci. |
| title_sort | genome wide discovery for diabetes dependent triglycerides associated loci |
| url | https://doi.org/10.1371/journal.pone.0275934 |
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