Severe hypertriglyceridemia is primarily polygenic

Slides:

Advertisements

Similar presentations

Wijtske Annema, PhD, Hendrik M

Advertisements

Genetics of common complex diseases: a view from Iceland

A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality Rishi K. Wadhera,

Lipid abnormalities in foreign-born and US-born patients in a medical group Jawali Jaranilla, MD, MPH, Terese DeFor, MS, Gabriela Vazquez Benitez, PhD,

Individual omega-9 monounsaturated fatty acids and mortality—The Ludwigshafen Risk and Cardiovascular Health Study Graciela E. Delgado, MSc, Bernhard.

Precision Cardiovascular Medicine: State of Genetic Testing

Tsung-Yu Tsai, MD, Yu-Chen Huang, MD

The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety and 1- year growth data Steve E. Humphries, PhD, FRCP, Jackie Cooper,

Kyoung-Bok Min, MD, PhD, Jin-Young Min, PhD

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: Results.

Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: A double-blinded, randomized, placebo controlled.

Performance of Common Analysis Methods for Detecting Low-Frequency Single Nucleotide Variants in Targeted Next-Generation Sequence Data David H. Spencer,

Psoriasis and suicidality: A systematic review and meta-analysis

Association of triglyceride-to-high density lipoprotein cholesterol ratio to cardiorespiratory fitness in men Gloria Lena Vega, PhD, Scott M. Grundy,

Omega-3 carboxylic acids in patients with severe hypertriglyceridemia: EVOLVE II, a randomized, placebo-controlled trial Erik S.G. Stroes, MD, PhD, Andrey.

A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality Rishi K. Wadhera,

Apolipoprotein E-containing high-density lipoprotein (HDL) modifies the impact of cholesterol-overloaded HDL on incident coronary heart disease risk:

Predictors of first-year statin medication discontinuation: A cohort study Heli Halava, MD, Risto Huupponen, MD, PhD, Jaana Pentti, BSc, Mika Kivimäki,

No evidence of large genetic effects on steroid response in asthma patients Michael Mosteller, PhD, Louise Hosking, BSc, Kay Murphy, PhD, Judong Shen,

Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study Tim Christen, MSc, Stella.

The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety and 1- year growth data Steve E. Humphries, PhD, FRCP, Jackie Cooper,

A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom Yize I. Wan, BMedSci, David P. Strachan,

Volume 18, Issue 9, Pages (February 2017)

Lipid and lipoprotein reference values from 133,450 Dutch Lifelines participants: Age- and gender-specific baseline lipid values and percentiles Jan.

Jonathan C. Cohen, PhD Journal of Clinical Lipidology

Volume 60, Issue 2, Pages (February 2014)

J. W. Balder, MD, PhD, P. J. Lansberg, MD, PhD, M. H. Hof, MSc, A

Whole-Gene Duplication of PCSK9 as a Novel Genetic Mechanism for Severe Familial Hypercholesterolemia Michael A. Iacocca, BSc, Jian Wang, MD, Samantha.

Jennifer Kerkhof, Laila C

Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred Rossella Spina,

Meredith Kilgore, PhD, Paul Muntner, PhD, J

Bariatric surgery improves lipoprotein profile in morbidly obese patients by reducing LDL cholesterol, apoB, and SAA/PON1 ratio, increasing HDL cholesterol,

Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial

Eveline Oestreicher Stock, MD, Christine T

Vitamin D deficiency in patients with chronic and acute urticaria: A systematic review and meta-analysis Tsung-Yu Tsai, MD, Yu-Chen Huang, MD Journal.

Paul D. Thompson, MD, John Rubino, MD, Matthew J. Janik, MD, Diane E

Ian S. Currie, BSc, MBChB, MD, PhD, Sonia J

Genome-wide Transcriptome Profiling Reveals the Functional Impact of Rare De Novo and Recurrent CNVs in Autism Spectrum Disorders Rui Luo, Stephan J.

An assessment by the Statin Intolerance Panel: 2014 update

Task-sharing interventions for cardiovascular risk reduction and lipid outcomes in low- and middle-income countries: A systematic review and meta-analysis

Gene-Expression Variation Within and Among Human Populations

Lipid and lipoprotein reference values from 133,450 Dutch Lifelines participants: Age- and gender-specific baseline lipid values and percentiles Jan.

Arpita Ghosh, Fei Zou, Fred A. Wright

A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients Stephen.

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: Results.

Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis Hayden N. Box, MD, Breann.

Volume 24, Issue 4, Pages (July 2018)

The risk of cardiovascular events with increased apolipoprotein CIII: A systematic review and meta-analysis Moritz C. Wyler von Ballmoos, MD, MPH, Bernhard.

Yousef Rezaei, MD American Journal of Kidney Diseases

Optimal high-density lipoprotein cholesterol cutoff for predicting cardiovascular disease: Comparison of the Korean and US National Health and Nutrition.

Cardiovascular autonomic dysfunction in women with polycystic ovary syndrome: a systematic review and meta-analysis Juan Gui, Rui-hao Wang Reproductive.

Fatal Anaphylaxis: Mortality Rate and Risk Factors

Characteristics of Neutral and Deleterious Protein-Coding Variation among Individuals and Populations Wenqing Fu, Rachel M. Gittelman, Michael J. Bamshad,

The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study Michael Davidson, MD, Michael Stevenson, RPh, PhD, Andrew Hsieh,

Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia Merel L. Hartgers, MD, Joep.

CAG Expansion in the Huntington Disease Gene Is Associated with a Specific and Targetable Predisposing Haplogroup Simon C. Warby, Alexandre Montpetit,

Sokunthea Peou, PharmD, Brittany Milliard-Hasting, MD, Sachin A

Familial hypercholesterolemia in a European Mediterranean population—Prevalence and clinical data from 2.5 million primary care patients Alberto Zamora,

The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection:

Simple renal cyst and abdominal aortic aneurysm

Primer of statistics in dental research: Part I

Diabetes is associated with an increased risk of cardiovascular disease in patients with familial hypercholesterolemia Martine Paquette, MSc, Sophie.

Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia Merel L. Hartgers, MD, Joep.

Individualized low-density lipoprotein cholesterol reduction with alirocumab titration strategy in heterozygous familial hypercholesterolemia: Results.

Tsung-Yu Tsai, MD, Yu-Chen Huang, MD

Figure 1. Identification of three tumour molecular subtypes in CIT and TCGA cohorts. We used CIT multi-omics data ( Figure 1. Identification of.

Clinical effectiveness of laparoscopic fundoplication in a U. S

No evidence of large genetic effects on steroid response in asthma patients Michael Mosteller, PhD, Louise Hosking, BSc, Kay Murphy, PhD, Judong Shen,

LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design Dirk J. Blom, MD, PhD, Zahi A. Fayad,

Jason L. Stein, Neelroop N. Parikshak, Daniel H. Geschwind Neuron

Presentation transcript:

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 80-88 (January 2019) DOI: 10.1016/j.jacl.2018.10.006 Copyright © 2018 National Lipid Association Terms and Conditions

Journal of Clinical Lipidology 2019 13, 80-88DOI: (10. 1016/j. jacl Copyright © 2018 National Lipid Association Terms and Conditions

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 2019 13, 80-88DOI: (10.1016/j.jacl.2018.10.006) Copyright © 2018 National Lipid Association Terms and Conditions

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 2.54. 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 2019 13, 80-88DOI: (10.1016/j.jacl.2018.10.006) Copyright © 2018 National Lipid Association Terms and Conditions

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 2019 13, 80-88DOI: (10.1016/j.jacl.2018.10.006) Copyright © 2018 National Lipid Association Terms and Conditions

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 2019 13, 80-88DOI: (10.1016/j.jacl.2018.10.006) Copyright © 2018 National Lipid Association Terms and Conditions