{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:59:21Z","timestamp":1760147961332,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort. Methods: A total of 113 AIH patients (i.e., 30 male\/83 female, median 57.9 years) were identified. In 81, genotyping of PNPLA3-rs738409, MBOAT7-rs626238, TM6SF2-rs58542926, and HSD17B13-rs72613567:TA, as well as both biochemical and clinical data at baseline and follow-up, were available. Results: The median time of follow-up was 2.8 years; five patients died and one underwent liver transplantation. The PNPLA3-G\/G homozygosity was linked to a worse treatment response when compared to wildtype [wt] (ALT 1.7 vs. 0.6 \u00d7 ULN, p &lt; 0.001). The MBOAT7-C\/C homozygosity was linked to non-response vs. wt and heterozygosity (p = 0.022). Male gender was associated with non-response (OR 14.5, p = 0.012) and a higher prevalence of PNPLA3 (G\/G vs. C\/G vs. wt 41.9\/40.0\/15.0% males, p = 0.03). The MBOAT7 wt was linked to less histological fibrosis (p = 0.008), while no effects for other SNPs were noted. A polygenic risk score was utilized comprising all the SNPs and correlated with the treatment response (p = 0.04). Conclusions: Our data suggest that genetic risk variants impact the treatment response of AIH in a gene-dosage-dependent manner. Furthermore, MBOAT7 and PNPLA3 mediated most of the observed effects, the latter explaining, in part, the predisposition of male subjects to worse treatment responses.<\/jats:p>","DOI":"10.3390\/jpm13030540","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T03:33:57Z","timestamp":1679024037000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variants Determine Treatment Response in Autoimmune Hepatitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0223-0323","authenticated-orcid":false,"given":"Stephan","family":"Zandanell","sequence":"first","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Balcar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-166X","authenticated-orcid":false,"given":"Georg","family":"Semmler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Schirmer","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Leitner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital, Paracelsus Medical University, Paracelsusstrasse 37, 5110 Oberndorf, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Rosenstatter","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3089-1222","authenticated-orcid":false,"given":"David","family":"Niederseer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, R\u00e4mistrasse 100, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Sotlar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6116-5517","authenticated-orcid":false,"given":"Anna-Maria","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Strasser","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Gensluckner","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Feldman","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7838-4532","authenticated-orcid":false,"given":"Christian","family":"Datz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital, Paracelsus Medical University, Paracelsusstrasse 37, 5110 Oberndorf, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmar","family":"Aigner","sequence":"additional","affiliation":[{"name":"First Department of Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1080\/00365520802130183","article-title":"Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: A nationwide study","volume":"43","author":"Werner","year":"2008","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.jhep.2013.10.020","article-title":"Autoimmune hepatitis in Denmark: Incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study","volume":"60","author":"Gronbaek","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1365-2036.2006.03104.x","article-title":"Type I autoimmune hepatitis: Clinical course and outcome in an Italian multicentre study","volume":"24","author":"Floreani","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_4","first-page":"59","article-title":"Influence of aetiology, clinical and histological features on survival in chronic active hepatitis: An analysis of 204 patients","volume":"62","author":"Keating","year":"1987","journal-title":"Q. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0016-5085(19)33223-8","article-title":"Clinical, biochemical, and histological remission of severe chronic active liver disease: A controlled study of treatments and early prognosis","volume":"63","author":"Soloway","year":"1972","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/hep.20732","article-title":"Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome","volume":"42","author":"Feld","year":"2005","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/j.1478-3231.2005.01121.x","article-title":"Early treatment response predicts the need for liver transplantation in autoimmune hepatitis","volume":"25","author":"Tan","year":"2005","journal-title":"Liver Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3109\/00365520903555861","article-title":"Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response","volume":"45","author":"Werner","year":"2010","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1002\/hep.27983","article-title":"Prediction of short- and long-term outcome in patients with autoimmune hepatitis","volume":"62","author":"Kirstein","year":"2015","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/hep.21787","article-title":"Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease","volume":"46","author":"Carpenter","year":"2007","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jhep.2009.02.026","article-title":"Rapidity of treatment response and outcome in type 1 autoimmune hepatitis","volume":"51","author":"Czaja","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1053\/j.gastro.2014.04.022","article-title":"Genome-wide association study identifies variants associated with autoimmune hepatitis type 1","volume":"147","author":"Zwiers","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/gene.2014.82","article-title":"HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1","volume":"16","author":"Zwiers","year":"2015","journal-title":"Genes Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1053\/gast.1997.v112.pm9178696","article-title":"Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis","volume":"112","author":"Strettell","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.3748\/wjg.v11.i12.1862","article-title":"Genetic distinctions between autoimmune hepatitis in Italy and North America","volume":"11","author":"Muratori","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10620-006-9495-4","article-title":"Evidence of a genetic basis for the different geographic occurrences of liver\/kidney microsomal antibody type 1 in hepatitis C","volume":"52","author":"Muratori","year":"2007","journal-title":"Dig. Dis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1053\/jhep.2002.32092","article-title":"Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease","volume":"35","author":"Ma","year":"2002","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/liv.14280","article-title":"Permanent immunosuppression in SLA\/LP-positive autoimmune hepatitis is required although overall response and survival are similar","volume":"40","author":"Zachou","year":"2020","journal-title":"Liver Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/apt.15722","article-title":"The PNPLA3 rs738409 GG genotype is associated with poorer prognosis in 239 patients with autoimmune hepatitis","volume":"51","author":"Mederacke","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24407","DOI":"10.1038\/s41598-021-03521-3","article-title":"MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis","volume":"11","author":"Janik","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/hep.24017","article-title":"Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians","volume":"53","author":"Stickel","year":"2011","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3417","article-title":"A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis","volume":"47","author":"Buch","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/hep.24283","article-title":"Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease","volume":"53","author":"Sookoian","year":"2011","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1038\/ncomms5309","article-title":"TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease","volume":"5","author":"Liu","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1053\/j.gastro.2016.01.032","article-title":"The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent","volume":"150","author":"Mancina","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1194\/jlr.P089953","article-title":"Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease","volume":"60","author":"Pirola","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa1712191","article-title":"A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease","volume":"378","author":"Cheng","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"18016","DOI":"10.1038\/nrdp.2018.16","article-title":"Haemochromatosis","volume":"4","author":"Brissot","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1055\/s-0031-1297926","article-title":"The impact of human gene polymorphisms on HCV infection and disease outcome","volume":"31","author":"Schaefer","year":"2011","journal-title":"Semin. Liver Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/B978-0-444-63625-6.00003-3","article-title":"The genetics of Wilson disease","volume":"142","author":"Chang","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/hep.22322","article-title":"Simplified criteria for the diagnosis of autoimmune hepatitis","volume":"48","author":"Hennes","year":"2008","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"847","DOI":"10.2174\/138955709788452676","article-title":"Diagnosis and therapy of autoimmune hepatitis","volume":"9","author":"Granito","year":"2009","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jhep.2021.12.041","article-title":"Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group","volume":"76","author":"Pape","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2015). EASL Clinical Practice Guidelines: Autoimmune hepatitis. J. Hepatol., 63, 971\u20131004.","DOI":"10.1016\/j.jhep.2015.06.030"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/hep.31065","article-title":"Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases","volume":"72","author":"Mack","year":"2020","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1111\/j.1365-2036.2005.02488.x","article-title":"Clinical features of type 1 autoimmune hepatitis in elderly Italian patients","volume":"21","author":"Granito","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.dld.2021.06.015","article-title":"PNPLA3 is the dominant SNP linked to liver disease severity at time of first referral to a tertiary center","volume":"54","author":"Balcar","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1002\/hep.29064","article-title":"The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B","volume":"65","author":"Thabet","year":"2017","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12757","DOI":"10.1038\/ncomms12757","article-title":"MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C","volume":"7","author":"Thabet","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/gutjnl-2020-320853","article-title":"Loss of hepatic Mboat7 leads to liver fibrosis","volume":"70","author":"Thangapandi","year":"2021","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jaut.2009.03.005","article-title":"Female predominance and X chromosome defects in autoimmune diseases","volume":"33","author":"Invernizzi","year":"2009","journal-title":"J. Autoimmun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"J109","DOI":"10.1016\/j.jaut.2011.10.003","article-title":"Autoimmune disease and gender: Plausible mechanisms for the female predominance of autoimmunity","volume":"38","author":"Quintero","year":"2012","journal-title":"J. Autoimmun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1365-2036.2006.03013.x","article-title":"Clinical features of Japanese male patients with type 1 autoimmune hepatitis","volume":"24","author":"Miyake","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jhep.2007.08.013","article-title":"Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis","volume":"48","author":"Underhill","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/hep.1840130415","article-title":"Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors","volume":"13","author":"Donaldson","year":"1991","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1111\/j.1572-0241.2002.05921.x","article-title":"Gender effects and synergisms with histocompatibility leukocyte antigens in type 1 autoimmune hepatitis","volume":"97","author":"Czaja","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jhep.2020.08.027","article-title":"rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis","volume":"74","author":"Teo","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.clinre.2019.12.006","article-title":"The MBOAT7 rs641738 variant is associated with an improved outcome in primary sclerosing cholangitis","volume":"44","author":"Freund","year":"2020","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.jhep.2020.11.024","article-title":"Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores","volume":"74","author":"Bianco","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.cgh.2021.05.056","article-title":"A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores","volume":"20","author":"Tavaglione","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/MED.0000000000000708","article-title":"Polygenic risk scores for the diagnosis and management of dyslipidemia","volume":"29","author":"Brunham","year":"2022","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41366-022-01168-2","article-title":"Dissecting the clinical relevance of polygenic risk score for obesity-a cross-sectional, longitudinal analysis","volume":"46","author":"Choe","year":"2022","journal-title":"Int. J. Obes."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41569-021-00638-w","article-title":"Clinical utility of polygenic risk scores for coronary artery disease","volume":"19","author":"Klarin","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sun, L., Pennells, L., Kaptoge, S., Nelson, C.P., Ritchie, S.C., Abraham, G., Arnold, M., Bell, S., Bolton, T., and Burgess, S. (2021). Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003498"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41576-018-0018-x","article-title":"The personal and clinical utility of polygenic risk scores","volume":"19","author":"Torkamani","year":"2018","journal-title":"Nat. Rev. Genet."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/3\/540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:21Z","timestamp":1760122641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/3\/540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jpm13030540"],"URL":"https:\/\/doi.org\/10.3390\/jpm13030540","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}