{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:44:34Z","timestamp":1792860274797,"version":"4.5.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R01DK082766"],"award-info":[{"award-number":["R01DK082766"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"national institute of diabetes and digestive and kidney diseases","doi-asserted-by":"publisher","award":["R01DK118427"],"award-info":[{"award-number":["R01DK118427"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"national human genome research institute","doi-asserted-by":"publisher","award":["NOT-HG-11-009"],"award-info":[{"award-number":["NOT-HG-11-009"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of-function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whether genetically increased plasma TG due to ApoC-III is causally associated with increased CAD risk is still unclear and inconsistent. The objectives of this study were to verify the cardioprotective role of earlier reported six\u00a0LoF variants of <jats:italic>APOC3<\/jats:italic> in South Asians and other multi-ethnic cohorts and to evaluate the causal association of TG raising common variants for increasing CAD risk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed gene-centric and Mendelian randomization analyses and evaluated the role of genetic variation encompassing <jats:italic>APOC3<\/jats:italic> for affecting circulating TG and the risk for developing CAD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>One rare LoF variant (rs138326449) with a 37% reduction in TG was associated with lowered risk for CAD in Europeans (<jats:italic>p<\/jats:italic>\u00a0=\u20090.007), but we could not confirm this association in Asian Indians (<jats:italic>p<\/jats:italic>\u00a0=\u20090.641).\u00a0Our data could not validate the cardioprotective role of other five LoF\u00a0variants analysed. A common variant rs5128 in the <jats:italic>APOC3<\/jats:italic> was strongly associated with elevated TG levels showing a <jats:italic>p<\/jats:italic>-value 2.8\u2009\u00d7\u200910<jats:sup>\u2212\u2009424<\/jats:sup>. Measures of plasma ApoC-III in a small subset of Sikhs revealed a 37% increase in ApoC-III concentrations among homozygous mutant carriers than the wild-type carriers of rs5128. A genetically instrumented per 1SD increment of plasma TG level of 15\u2009mg\/dL would cause a mild increase (3%) in the risk for CAD (<jats:italic>p<\/jats:italic>\u00a0=\u20090.042).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results highlight the challenges of inclusion of rare variant information in clinical risk assessment and the generalizability of implementation of ApoC-III inhibition for treating atherosclerotic disease. More studies would be needed to confirm whether genetically raised TG and ApoC-III concentrations would increase CAD risk.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12944-021-01531-8","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T13:03:09Z","timestamp":1632229389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups"],"prefix":"10.1186","volume":"20","author":[{"given":"Shiwali","family":"Goyal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Tanigawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Fang","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcio","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Chainakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Garcia","family":"Ramiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanel","family":"Seraphin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair","family":"Apple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Muniu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Peralta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Lehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarju","family":"Ralhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet S.","family":"Wander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Rup","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narinder K.","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Sidorov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin D.","family":"Peyton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piers R.","family":"Blackett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E.","family":"Curran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Shyong","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"van Dam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindranath","family":"Duggirala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Blangero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charumathi","family":"Sabanayagam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaspal S.","family":"Kooner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Rivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Aston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharambir K.","family":"Sanghera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"issue":"2","key":"1531_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/j.1365-2796.2012.02516.x","volume":"272","author":"RP Surendran","year":"2012","unstructured":"Surendran RP, Visser ME, Heemelaar S, Wang J, Peter J, Defesche JC, et al. Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. J Intern Med. 2012;272(2):185\u201396.","journal-title":"J Intern Med"},{"key":"1531_CR2","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3389\/fendo.2020.00616","volume":"11","author":"LS Santos-Baez","year":"2020","unstructured":"Santos-Baez LS, Ginsberg HN. Hypertriglyceridemia-causes, significance, and approaches to therapy. Front Endocrinol. 2020;11:616.","journal-title":"Front Endocrinol"},{"issue":"6","key":"1531_CR3","doi-asserted-by":"publisher","first-page":"443","DOI":"10.2165\/00002018-200124060-00003","volume":"24","author":"AK Mantel-Teeuwisse","year":"2001","unstructured":"Mantel-Teeuwisse AK, Kloosterman JM. Maitland-van der zee AH, Klungel OH, Porsius AJ, de Boer a. drug-induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels. Drug Saf. 2001;24(6):443\u201356.","journal-title":"Drug Saf"},{"key":"1531_CR4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.atherosclerosis.2017.10.025","volume":"267","author":"A Wolska","year":"2017","unstructured":"Wolska A, Dunbar RL, Freeman LA, Ueda M, Amar MJ, Sviridov DO, et al. Apolipoprotein C-II: new findings related to genetics, biochemistry, and role in triglyceride metabolism. Atherosclerosis. 2017;267:49\u201360.","journal-title":"Atherosclerosis"},{"issue":"16","key":"1531_CR5","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1161\/01.CIR.102.16.1886","volume":"102","author":"FM Sacks","year":"2000","unstructured":"Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the cholesterol and recurrent events (CARE) trial. Circulation. 2000;102(16):1886\u201392.","journal-title":"Circulation"},{"issue":"6","key":"1531_CR6","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1097\/MOL.0000000000000710","volume":"31","author":"A Wolska","year":"2020","unstructured":"Wolska A, Yang ZH, Remaley AT. Hypertriglyceridemia: new approaches in management and treatment. Curr Opin Lipidol. 2020;31(6):331\u20139.","journal-title":"Curr Opin Lipidol"},{"issue":"24","key":"1531_CR7","doi-asserted-by":"publisher","first-page":"e285","DOI":"10.1016\/j.jacc.2018.11.003","volume":"73","author":"SM Grundy","year":"2019","unstructured":"Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the Management of Blood Cholesterol: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285\u2013350.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"1531_CR8","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","volume":"41","author":"F Mach","year":"2020","unstructured":"Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC\/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111\u201388.","journal-title":"Eur Heart J"},{"issue":"1","key":"1531_CR9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0021-9150(95)05791-9","volume":"122","author":"E Koren","year":"1996","unstructured":"Koren E, Corder C, Mueller G, Centurion H, Hallum G, Fesmire J, et al. Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease. Atherosclerosis. 1996;122(1):105\u201315.","journal-title":"Atherosclerosis"},{"issue":"8","key":"1531_CR10","doi-asserted-by":"publisher","first-page":"3949","DOI":"10.1210\/jc.2003-032056","volume":"89","author":"JS Cohn","year":"2004","unstructured":"Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab. 2004;89(8):3949\u201355.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1531_CR11","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.arcmed.2006.10.013","volume":"38","author":"M Miller","year":"2007","unstructured":"Miller M, Rhyne J, Chen H, Beach V, Ericson R, Luthra K, et al. APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome. Arch Med Res. 2007;38(4):444\u201351.","journal-title":"Arch Med Res"},{"key":"1531_CR12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/1471-2350-8-80","volume":"8","author":"RL Pollex","year":"2007","unstructured":"Pollex RL, Ban MR, Young TK, Bjerregaard P, Anand SS, Yusuf S, et al. Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample. BMC Med Genet. 2007;8:80.","journal-title":"BMC Med Genet"},{"issue":"7307","key":"1531_CR13","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/nature09270","volume":"466","author":"TM Teslovich","year":"2010","unstructured":"Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466(7307):707\u201313.","journal-title":"Nature"},{"issue":"5","key":"1531_CR14","doi-asserted-by":"publisher","first-page":"e37056","DOI":"10.1371\/journal.pone.0037056","volume":"7","author":"TR Braun","year":"2012","unstructured":"Braun TR, Been LF, Singhal A, Worsham J, Ralhan S, Wander GS, et al. A replication study of GWAS-derived lipid genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides. PLoS One. 2012;7(5):e37056.","journal-title":"PLoS One"},{"issue":"5908","key":"1531_CR15","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1126\/science.1161524","volume":"322","author":"TI Pollin","year":"2008","unstructured":"Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science. 2008;322(5908):1702\u20135.","journal-title":"Science"},{"issue":"1","key":"1531_CR16","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJMoa1307095","volume":"371","author":"I Blood","year":"2014","unstructured":"Tg, Hdl Working Group of the Exome Sequencing Project NHL, Blood I, Crosby J, Peloso GM, Auer PL, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371(1):22\u201331.","journal-title":"N Engl J Med"},{"issue":"11","key":"1531_CR17","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/S0022-2275(20)31969-6","volume":"41","author":"H Liu","year":"2000","unstructured":"Liu H, Labeur C, Xu CF, Ferrell R, Lins L, Brasseur R, et al. Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr. J Lipid Res. 2000;41(11):1760\u201371.","journal-title":"J Lipid Res"},{"issue":"1","key":"1531_CR18","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa1308027","volume":"371","author":"AB Jorgensen","year":"2014","unstructured":"Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371(1):32\u201341.","journal-title":"N Engl J Med"},{"issue":"12","key":"1531_CR19","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1161\/CIR.0b013e3181f22af4","volume":"122","author":"LP Palaniappan","year":"2010","unstructured":"Palaniappan LP, Araneta MR, Assimes TL, Barrett-Connor EL, Carnethon MR, Criqui MH, et al. Call to action: cardiovascular disease in Asian Americans: a science advisory from the American Heart Association. Circulation. 2010;122(12):1242\u201352.","journal-title":"Circulation"},{"issue":"11","key":"1531_CR20","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1007\/s00125-006-0393-2","volume":"49","author":"NG Forouhi","year":"2006","unstructured":"Forouhi NG, Sattar N, Tillin T, McKeigue PM, Chaturvedi N. Do known risk factors explain the higher coronary heart disease mortality in south Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK. Diabetologia. 2006;49(11):2580\u20138.","journal-title":"Diabetologia"},{"issue":"5","key":"1531_CR21","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.2337\/db12-1077","volume":"62","author":"R Saxena","year":"2013","unstructured":"Saxena R, Saleheen D, Been LF, Garavito ML, Braun T, Bjonnes A, et al. Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. Diabetes. 2013;62(5):1746\u201355.","journal-title":"Diabetes"},{"issue":"3","key":"1531_CR22","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1161\/CIRCGENETICS.113.000412","volume":"7","author":"R Saxena","year":"2014","unstructured":"Saxena R, Bjonnes A, Prescott J, Dib P, Natt P, Lane J, et al. Genome-wide association study identifies variants in casein kinase II (CSNK2A2) to be associated with leukocyte telomere length in a Punjabi Sikh diabetic cohort. Circ Cardiovasc Genet. 2014;7(3):287\u201395.","journal-title":"Circ Cardiovasc Genet"},{"key":"1531_CR23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.jsbmb.2015.12.014","volume":"158","author":"BR Sapkota","year":"2016","unstructured":"Sapkota BR, Hopkins R, Bjonnes A, Ralhan S, Wander GS, Mehra NK, et al. Genome-wide association study of 25(OH) vitamin D concentrations in Punjabi Sikhs: results of the Asian Indian diabetic heart study. J Steroid Biochem Mol Biol. 2016;158:149\u201356.","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"10","key":"1531_CR24","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/ng.921","volume":"43","author":"JS Kooner","year":"2011","unstructured":"Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang WH, Frossard P, et al. Genome-wide association study in individuals of south Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet. 2011;43(10):984\u2013U94.","journal-title":"Nat Genet"},{"issue":"4","key":"1531_CR25","doi-asserted-by":"publisher","first-page":"e1001363","DOI":"10.1371\/journal.pgen.1001363","volume":"7","author":"X Sim","year":"2011","unstructured":"Sim X, Ong RT, Suo C, Tay WT, Liu J, Ng DP, et al. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet. 2011;7(4):e1001363.","journal-title":"PLoS Genet"},{"issue":"5","key":"1531_CR26","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.ajhg.2020.03.007","volume":"106","author":"C DeBoever","year":"2020","unstructured":"DeBoever C, Tanigawa Y, Aguirre M, McInnes G, Lavertu A, Rivas MA. Assessing digital Phenotyping to enhance genetic studies of human diseases. Am J Hum Genet. 2020;106(5):611\u201322.","journal-title":"Am J Hum Genet"},{"key":"1531_CR27","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/1471-2288-11-141","volume":"11","author":"EE Nang","year":"2011","unstructured":"Nang EE, Gitau Ngunjiri SA, Wu Y, Salim A, Tai ES, Lee J, et al. Validity of the international physical activity questionnaire and the Singapore prospective study program physical activity questionnaire in a multiethnic urban asian population. BMC Med Res Methodol. 2011;11:141.","journal-title":"BMC Med Res Methodol"},{"issue":"7726","key":"1531_CR28","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK biobank resource with deep phenotyping and genomic data. Nature. 2018;562(7726):203\u20139.","journal-title":"Nature"},{"issue":"9","key":"1531_CR29","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1161\/01.CIR.94.9.2159","volume":"94","author":"BD Mitchell","year":"1996","unstructured":"Mitchell BD, Kammerer CM, Blangero J, Mahaney MC, Rainwater DL, Dyke B, et al. Genetic and environmental contributions to cardiovascular risk factors in Mexican Americans. The San Antonio family heart study. Circulation. 1996;94(9):2159\u201370.","journal-title":"Circulation"},{"issue":"4","key":"1531_CR30","doi-asserted-by":"publisher","first-page":"104618","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104618","volume":"29","author":"E Sidorov","year":"2020","unstructured":"Sidorov E, Bejar C, Xu C, Ray B, Reddivari L, Chainakul J, et al. Potential metabolite biomarkers for acute versus chronic stage of ischemic stroke: a pilot study. J Stroke Cerebrovasc Dis. 2020;29(4):104618.","journal-title":"J Stroke Cerebrovasc Dis"},{"issue":"10","key":"1531_CR31","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/ng.3656","volume":"48","author":"S Das","year":"2016","unstructured":"Das S, Forer L, Schonherr S, Sidore C, Locke AE, Kwong A, et al. Next-generation genotype imputation service and methods. Nat Genet. 2016;48(10):1284\u20137.","journal-title":"Nat Genet"},{"issue":"17","key":"1531_CR32","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26(17):2190\u20131.","journal-title":"Bioinformatics"},{"issue":"18","key":"1531_CR33","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","volume":"26","author":"RJ Pruim","year":"2010","unstructured":"Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26(18):2336\u20137.","journal-title":"Bioinformatics"},{"key":"1531_CR34","volume-title":"Principles of biostatistics CENGAGE learning (3\/9\/2000)","author":"K PMaG","year":"2000","unstructured":"K PMaG. Principles of biostatistics CENGAGE learning (3\/9\/2000); 2000."},{"issue":"1","key":"1531_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"GD Smith","year":"2003","unstructured":"Smith GD, Ebrahim S. 'Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1\u201322.","journal-title":"Int J Epidemiol"},{"issue":"11","key":"1531_CR36","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","volume":"27","author":"P Sekula","year":"2016","unstructured":"Sekula P, Del Greco MF, Pattaro C, Kottgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27(11):3253\u201365.","journal-title":"J Am Soc Nephrol"},{"issue":"8","key":"1531_CR37","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1161\/ATVBAHA.115.305415","volume":"35","author":"A Qamar","year":"2015","unstructured":"Qamar A, Khetarpal SA, Khera AV, Qasim A, Rader DJ, Reilly MP. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics. Arterioscler Thromb Vasc Biol. 2015;35(8):1880\u20138.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"5","key":"1531_CR38","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1056\/NEJMoa1400283","volume":"373","author":"D Gaudet","year":"2015","unstructured":"Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, et al. Antisense inhibition of Apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373(5):438\u201347.","journal-title":"N Engl J Med"},{"key":"1531_CR39","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.atherosclerosis.2020.08.017","volume":"311","author":"G Silbernagel","year":"2020","unstructured":"Silbernagel G, Scharnagl H, Kleber ME, Hoffmann MM, Delgado G, Stojakovic T, et al. Common APOC3 variants are associated with circulating ApoC-III and VLDL cholesterol but not with total apolipoprotein B and coronary artery disease. Atherosclerosis. 2020;311:84\u201390.","journal-title":"Atherosclerosis"},{"issue":"3","key":"1531_CR40","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1097\/MOL.0b013e328352dc70","volume":"23","author":"Z Yao","year":"2012","unstructured":"Yao Z, Wang Y. Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production. Curr Opin Lipidol. 2012;23(3):206\u201312.","journal-title":"Curr Opin Lipidol"},{"issue":"R2","key":"1531_CR41","doi-asserted-by":"publisher","first-page":"R151","DOI":"10.1093\/hmg\/ddn263","volume":"17","author":"RS Cooper","year":"2008","unstructured":"Cooper RS, Tayo B, Zhu X. Genome-wide association studies: implications for multiethnic samples. Hum Mol Genet. 2008;17(R2):R151\u20135.","journal-title":"Hum Mol Genet"},{"issue":"7649","key":"1531_CR42","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature22034","volume":"544","author":"D Saleheen","year":"2017","unstructured":"Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA, et al. Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature. 2017;544(7649):235\u20139.","journal-title":"Nature"},{"issue":"Suppl 3","key":"1531_CR43","first-page":"66","volume":"11","author":"DC Crawford","year":"2018","unstructured":"Crawford DC, Restrepo NA, Diggins KE, Farber-Eger E, Wells QS. Frequency and phenotype consequence of APOC3 rare variants in patients with very low triglyceride levels. BMC Med Genet. 2018;11(Suppl 3):66.","journal-title":"BMC Med Genet"},{"issue":"5","key":"1531_CR44","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1161\/01.ATV.0000066131.01313.EB","volume":"23","author":"SJ Lee","year":"2003","unstructured":"Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing Apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003;23(5):853\u20138.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"2","key":"1531_CR45","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0021-9150(03)00007-8","volume":"167","author":"SJ Lee","year":"2003","unstructured":"Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM. Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. Atherosclerosis. 2003;167(2):293\u2013302.","journal-title":"Atherosclerosis"},{"issue":"7","key":"1531_CR46","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/gepi.21998","volume":"40","author":"S Burgess","year":"2016","unstructured":"Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40(7):597\u2013608.","journal-title":"Genet Epidemiol"},{"key":"1531_CR47","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.mgene.2016.04.004","volume":"9","author":"Y Li","year":"2016","unstructured":"Li Y, Li C, Gao J. Apolipoprotein C3 gene variants and the risk of coronary heart disease: a meta-analysis. Meta Gene. 2016;9:104\u20139.","journal-title":"Meta Gene"}],"container-title":["Lipids in Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-021-01531-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12944-021-01531-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-021-01531-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T16:13:44Z","timestamp":1632240824000},"score":1,"resource":{"primary":{"URL":"https:\/\/lipidworld.biomedcentral.com\/articles\/10.1186\/s12944-021-01531-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,21]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1531"],"URL":"https:\/\/doi.org\/10.1186\/s12944-021-01531-8","relation":{},"ISSN":["1476-511X"],"issn-type":[{"value":"1476-511X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,21]]},"assertion":[{"value":"29 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All AIDHS\/SDS protocols and consent documents were reviewed and approved by the University of Oklahoma Health Science Center\u2019s Institutional Review Board (IRB) as well as the Human Subject Protection (Ethics) committees at the participating hospitals and institutes in India. The LOLIPOP study is approved by the National Research Ethics Service (07\/H0712\/150) and all participants gave written informed consent at enrollment. The SAFHS and SAFDGS study-specific protocols have been approved by the Institutional Review Boards of the University of Texas Health San Antonio and the University of Texas Rio Grande Valley, and informed consent was obtained from all SAFHS and SAFDGS participants, respectively. Ethics approval for the UKBB was obtained from the North West Centre for Research Ethics Committee (11\/NW\/0382). All the participants of UKBB provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"NA.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"113"}}