1. Severe hypertriglyceridemia is primarily polygenic
Jacqueline S. Dron, BSc, Jian Wang, MD, Henian Cao, MD, PhD, Adam D. McIntyre, BSc, Michael A. Iacocca, BSc, Jyler R. Menard, BSc, Irina Movsesyan, PhD, Mary J. Malloy, MD, Clive R. Pullinger, PhD, John P. Kane, MD, Robert A. Hegele, MD 
Journal of Clinical Lipidology 
Volume 13, Issue 1, Pages (January 2019)
DOI: /j.jacl
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2. Journal of Clinical Lipidology 2019 13, 80-88DOI: (10. 1016/j. jacl
Copyright © 2018 National Lipid Association Terms and Conditions

3. Figure 1
Breakdown of rare variants found in patients with severe HTG and controls. The most common type of rare variant across all cohorts was single heterozygous variants. Biallelic (homozygous or compound heterozygous) variants and CNVs were found exclusively in the HTG patient cohorts. CNV, copy-number variant.
Journal of Clinical Lipidology  , 80-88DOI: ( /j.jacl )
Copyright © 2018 National Lipid Association Terms and Conditions

4. Figure 2
Accumulation of TG-raising alleles across 16 SNP loci. Violin plots demonstrate the distribution of PRSs calculated across the reference 1KG cohort (N = 503), cohort 1 (N = 251), cohort 2 (N = 312), and the combined patient cohort (N = 563). Patients with an “extreme” accumulation of TG-raising alleles are defined as having scores above the 90th percentile threshold (≥1.49) in the reference 1KG cohort, which is illustrated by the hashed line. The percentage of patients with scores above the 90th percentile is indicated above the hashed line. The theoretical range of scores is from 0 to Black diamonds indicate the mean PRS of the group. The mean PRS ± SD for each group is listed beside the corresponding plot; the mean PRS for each patient group was significantly greater than the mean PRS for the 1KG cohort (P < .0001). For additional information on how to interpret violin plots in the context of PRSs, please refer to the review by Dron et al.26 PRS, polygenic risk score; SD, standard deviation.
Journal of Clinical Lipidology  , 80-88DOI: ( /j.jacl )
Copyright © 2018 National Lipid Association Terms and Conditions

5. Figure 3
Comparison of genetic profiles across cohorts. The outer, middle, and inner rings represent cohort 1 (N = 251), cohort 2 (N = 312), and the reference 1KG (N = 503) cohort, respectively. The prevalence of each type of genetic determinant is indicated. The most common genetic feature across all cohorts is an extreme PRS, reflecting an extreme accumulation of TG-raising alleles at multiple SNP loci. Only the patient cohorts contain biallelic variants, which are the molecular hallmark of monogenic FCS. CNV, copy-number variant; FCS, familial chylomicronemia syndrome; PRS, polygenic risk score; TG, triglyceride.
Journal of Clinical Lipidology  , 80-88DOI: ( /j.jacl )
Copyright © 2018 National Lipid Association Terms and Conditions

6. Figure 4
Forest plots of the ORs for different genetic determinants of HTG. The ORs for each cohort are defined for rare SNVs and CNVs, PRSs, and all determinants. Squares indicate the OR for cohort 1 (N = 251) and cohort 2 (N = 312) compared with the reference 1KG cohort (N = 503). The diamond indicates the OR for the combined patient cohort (N = 563). The dashed line indicates an OR of 1.0. Error bars represent 95% confidence intervals. P-values were generated from one-tailed Fisher's exact tests. 1KG, 1000 Genomes Project; CI, confidence interval; CNVs, copy-number variants; NS, not significant; OR, odds ratio; PRS, polygenic risk score; SNVs, single-nucleotide variants.
Journal of Clinical Lipidology  , 80-88DOI: ( /j.jacl )
Copyright © 2018 National Lipid Association Terms and Conditions