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In young adulthood, the 22q11.2 microdeletion conveys a 2-fold increased risk for mild-moderate hypertriglyceridemia. This study aimed to assess the role of the TG-PRS in individuals with this elevated baseline risk for mild-moderate hypertriglyceridemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied a deeply phenotyped cohort of adults (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009157, median age 34\u00a0years) with a 22q11.2 microdeletion and available genome sequencing, lipid level, and other clinical data. The association between a previously developed TG-PRS and TG levels was assessed using a multivariable regression model adjusting for effects of sex, BMI, and other covariates. We also constructed receiver operating characteristic (ROC) curves using logistic regression models to assess the ability of TG-PRS and significant clinical variables to predict mild-moderate hypertriglyceridemia status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The TG-PRS was a significant predictor of TG-levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.52E-04), along with male sex and BMI, in a multivariable model (p\n                      <jats:sub>model<\/jats:sub>\n                      \u2009=\u20097.26E-05). The effect of TG-PRS appeared to be slightly stronger in individuals with obesity (BMI\u2009\u2265\u200930) (beta\u2009=\u20090.4617) than without (beta\u2009=\u20090.1778), in a model unadjusted for other covariates (\n                      <jats:italic>p<\/jats:italic>\n                      -interaction\u2009=\u20090.045). Among ROC curves constructed, the inclusion of TG-PRS, sex, and BMI as predictor variables produced the greatest area under the curve (0.749) for classifying those with mild-moderate hypertriglyceridemia, achieving an optimal sensitivity and specificity of 0.746 and 0.707, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results demonstrate that in addition to significant effects of sex and BMI, genome-wide common variation captured in a PRS also contributes to the variable expression of the 22q11.2 microdeletion with respect to elevated TG levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-023-01717-2","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T16:20:30Z","timestamp":1699460430000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polygenic risk for triglyceride levels in the presence of a high impact rare variant"],"prefix":"10.1186","volume":"16","author":[{"given":"Shengjie","family":"Ying","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Heung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1128-008X","authenticated-orcid":false,"given":"Bhooma","family":"Thiruvahindrapuram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Worrawat","family":"Engchuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Blagojevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-6472","authenticated-orcid":false,"given":"Zhaolei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":false,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-4968","authenticated-orcid":false,"given":"Ryan K. 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