{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:56:57Z","timestamp":1772215017874,"version":"3.50.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL142711, R01HL148050, R01HL151283, R01HL127564, R01HL148565, R01HL151152, R01DK125782"],"award-info":[{"award-number":["R01HL142711, R01HL148050, R01HL151283, R01HL127564, R01HL148565, R01HL151152, R01DK125782"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["TNE-18CVD04"],"award-info":[{"award-number":["TNE-18CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL127564 and R01HL142711"],"award-info":[{"award-number":["R01HL127564 and R01HL142711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019s Q-test and we validated the significantly associated variants in the Mass General Brigham Biobank (MGBB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (I\n                      <jats:sup>2<\/jats:sup>\n                      = 98.4%; p\n                      <jats:sub>heterogeneity<\/jats:sub>\n                      = 2.1x10\n                      <jats:sup>-15<\/jats:sup>\n                      ), 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\n                      <jats:italic>HLA-DQB1<\/jats:italic>\n                      gene, between\n                      <jats:italic>HLA<\/jats:italic>\n                      -\n                      <jats:italic>DQB1<\/jats:italic>\n                      and\n                      <jats:italic>HLA<\/jats:italic>\n                      -\n                      <jats:italic>DQA2<\/jats:italic>\n                      genes. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (p\n                      <jats:sub>heterogeneity<\/jats:sub>\n                      = 9.5x10\n                      <jats:sup>-3<\/jats:sup>\n                      ). 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion, we identified an intergenic variant near\n                      <jats:italic>HLA-DQB1\/DQA2<\/jats:italic>\n                      significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0275934","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T13:27:01Z","timestamp":1666358821000},"page":"e0275934","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genome-wide discovery for diabetes-dependent triglycerides-associated loci"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-9254","authenticated-orcid":true,"given":"Margaret Sunitha","family":"Selvaraj","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1228-1674","authenticated-orcid":true,"given":"Kaavya","family":"Paruchuri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Haidermota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7139-6899","authenticated-orcid":true,"given":"Rachel","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-7793","authenticated-orcid":true,"given":"Stephen S.","family":"Rich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-8636","authenticated-orcid":true,"given":"Gina M.","family":"Peloso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8402-7435","authenticated-orcid":true,"given":"Pradeep","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"pone.0275934.ref001","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"P. 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