A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia

Vanhoye, Xavier; Bardel, Claire; Moulin, Philippe; Rollat‐Farnier, Pierre‐Antoine; Muntaner, Manon; Marmontel, Oriane; Dumont, Sabrina; Charrière, Sybil; Cornélis, François; Ducluzeau, Pierre Henri; Fonteille, Annie; Nobécourt, Estelle; Peretti, Noël; Schillo, F.; Wargny, Matthieu; Cariou, Bertrand; Meirhaeghe, Aline; Filippo, Mathilde Di

doi:10.1016/j.trsl.2022.12.002

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…However, due to different genetic background PRS set-up in a population cannot be applied to another, making the PRS poorly generalizable [ 80 ] and suggesting creating different PRS. In addition, thanks to NGS, PRS including more and more polymorphisms were constructed with the aim to improve diagnostic ability; the most recent score was constructed on 165 polymorphism, promising to outperform the previous ones [ 81 ].…”

Section: Genetics and Molecular Basismentioning

confidence: 99%

Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis

Taranto

Fortunato

2023

IJMS

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Genetics of Familial Hypercholesterolemia (FH) is ascribable to pathogenic variants in genes encoding proteins leading to an impaired LDL uptake by the LDL receptor (LDLR). Two forms of the disease are possible, heterozygous (HeFH) and homozygous (HoFH), caused by one or two pathogenic variants, respectively, in the three main genes that are responsible for the autosomal dominant disease: LDLR, APOB and PCSK9 genes. The HeFH is the most common genetic disease in humans, being the prevalence about 1:300. Variants in the LDLRAP1 gene causes FH with a recessive inheritance and a specific APOE variant was described as causative of FH, contributing to increase FH genetic heterogeneity. In addition, variants in genes causing other dyslipidemias showing phenotypes overlapping with FH may mimic FH in patients without causative variants (FH-phenocopies; ABCG5, ABCG8, CYP27A1 and LIPA genes) or act as phenotype modifiers in patients with a pathogenic variant in a causative gene. The presence of several common variants was also considered a genetic basis of FH and several polygenic risk scores (PRS) have been described. The presence of a variant in modifier genes or high PRS in HeFH further exacerbates the phenotype, partially justifying its variability among patients. This review aims to report the updates on the genetic and molecular bases of FH with their implication for molecular diagnosis.

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Section: Genetics and Molecular Basismentioning

confidence: 99%

Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis

Taranto

Fortunato

2023

IJMS

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“…We calculated a polygenic risk score (PRS) based on a 165-SNP score developed by Vanhoye et. al [23]. After merging the 165-SNP panel with our variants, we retrieved 124 SNPs along with their corresponding weights and harmonized risk alleles [24] to ensure consistency in direction of SNP effects.…”

Section: Sensitivity Analysis On Ldl Levels With Adjustment For Genet...mentioning

confidence: 99%

Effects of short-term restriction of animal products on blood biomarkers and cardiovascular disease risk

Loizidou

Barbounakis

Glentis

et al. 2023

Preprint

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Background. Dietary restriction (DR) is gaining ground as a means to prevent and treat a range of conditions and diseases. In our study we address the impact of periodic abstinence from animal products (periodic veganism) on markers of health. Methods. We profiled 200 periodic vegan (PV) individuals who switch between an omnivorous and a vegan diet, abstaining for 180–200 days annually, in a highly structured manner. We also profiled 211 non–vegan (NV), omnivorous individuals. Traits were measured at two timepoints, the first capturing a period of omnivory for both groups, the second capturing a period during which PV individuals only had followed a vegan diet for three to four weeks. We report results on blood lipids (total, LDL, and HDL cholesterol, triglycerides), glucose metabolism (glucose, insulin, HBA1c), renal function (urea, uric acid, creatinine), liver function (AST, ALT, γ–GT), bone/liver function (ALP), thyroid function (TSH), inflammation (CRP), complete blood counts, anthropometric traits and blood pressure. Results. Upon DR, PV individuals display decreased levels of total and LDL cholesterol [both β=-0.3, 95% CI:(-0.4, -0.2) mmol/L] and of CRP [β=-1.3, 95% CI:(-2.1, -0.5) mg/L] which drops by 28%. Compared to NV, PV individuals display consistently lower counts of total white blood cells (WBC) [β=-0.4, 95% C.I:(-0.6,-0.3) K/μL] and neutrophils [β=-0.4, 95% C.I:(-0.5,-0.2) x10^3/μl], but higher levels of ALP [β=5.9, 95% C.I:(2.7,9.1) U/L], suggesting detrimental effects on bone health. Conclusion. Harnessing dietary intake to prevent and treat disease is a promising approach that should also be explored for synergies with pharmacological therapies.

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“…В этом контексте особый интерес представляет одно из недавних исследований, в котором была разработана ШГР полигенной ГХС на основе всего 165 ВНП, ассоциированных с уровнем холестерина липопротеинов низкой плотности, что делает возможным ее применение с использованием таргетных панелей для секвенирования нового поколения. Данная ШГР объясняла 19 % вариабельности признака [17].…”

Section: том 3 № 5 2023unclassified

Personalized prevention: possibilities and limitations of polygenic risk assessment

Drapkina,

Limonova,

Garbuzova

et al. 2023

jour

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Noncommunicable diseases (NCDs) are the leading cause of mortality worldwide, with a vast majority of them having a multifactorial etiology, including genetics. That is why implementation of polygenic risk scores (PRS) in clinical practice with the aim of development of individual strategies for NCDs prevention seems promising. In this review we will discuss development and possible implications of PRSs.

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A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia

Cited by 5 publications

References 36 publications

Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis

Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis

Effects of short-term restriction of animal products on blood biomarkers and cardiovascular disease risk

Personalized prevention: possibilities and limitations of polygenic risk assessment

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