Additional value of a combined genetic risk score to standard cardiovascular stratification

Pereira, Andreia; Mendonça, Maria Isabel; Borges, S; Silva, Célia Regina Sousa da; Freitas, S; Henriques, E; Rodrigues, M; Freitas, Ana Isabel; Guerra, G; Freitas, Carolina; Pereira, Décio; Brehm, António; Reis, Roberto Palma dos

doi:10.1590/1678-4685-gmb-2017-0173

Cited by 8 publications

(5 citation statements)

References 34 publications

(36 reference statements)

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“…The extent to which CAD GRSs can improve risk prediction beyond established clinical risk scores requires further investigation 47 . However, a major advantage of assessing germline genetic variation for cardiovascular risk assessment is that it only needs to be measured once and can be measured early in life, allowing for earlier intervention before other clinical risk factors may emerge 7,25,46 .…”

Section: Disucssionmentioning

confidence: 99%

“…Recent work suggests that genomic risk scores (GRSs), which summarize the association of millions of common genetic variants with risk of CAD into a single value, may be a useful tool for improving risk prediction of CAD 7,[22][23][24][25] . Here we tested the hypothesis that, among individuals with elevated lipoprotein(a), the risk of CAD would be modulated by a GRS for CAD, and that this may be useful for risk stratification.…”

Section: Introductionmentioning

confidence: 99%

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Polygenic modulation of lipoprotein(a)-associated cardiovascular risk

Trinder¹,

Brunham

2020

Preprint

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Aims: Elevated levels of lipoprotein(a) are one of the strongest inherited risk factors for coronary artery disease (CAD). However, there is variability in cardiovascular risk among individuals with elevated lipoprotein(a). The sources of this variability are incompletely understood. We assessed the effects of a genomic risk score (GRS) for CAD on risk of myocardial infarction among individuals with elevated lipoprotein(a). Methods: We calculated CAD GRSs for 408,896 individuals of British white ancestry from the UK Biobank using 6.27 million common genetic variants. Lipoprotein(a) levels were measured in 310,020 individuals. The prevalence and risk of myocardial infarction versus CAD GRS percentiles were compared for individuals with and without elevated lipoprotein(a) defined as ≥120 or 168 nmol/L (≈50 or 70 mg/dL, respectively). Results: Individuals with elevated lipoprotein(a) displayed significantly greater CAD GRSs than individuals without elevated lipoprotein(a), which was largely dependent on the influence of genetic variants within or near the LPA gene. Continuous levels of CAD GRS percentile were significantly associated with risk of myocardial infarction for individuals with elevated lipoprotein(a). Notably, the risk of myocardial infarction for males with elevated lipoprotein(a) levels, but a CAD GRS percentile in the lower quintile (<20th percentile), was less than the overall risk of myocardial infarction for males with non-elevated lipoprotein(a) levels (hazard ratio [95% CI]: 0.79 [0.64-0.97], p=0.02). Similar results were observed for females. Conclusion: These data suggest that CAD genomic scores influence cardiovascular risk among individuals with elevated lipoprotein(a) and may aid in identifying candidates for preventive therapies.

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Section: Disucssionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polygenic modulation of lipoprotein(a)-associated cardiovascular risk

Trinder¹,

Brunham

2020

Preprint

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“…A review study identified that genetic risk scores have aggregated multiple sets of results into a single genetic predictor for cardiovascular diseases (Smith et al., 2015). It is important to consider the interaction of genes in the body (Dudbridge et al., 2017), and studies have identified a higher predictive value of the genetic risk score for cardiovascular risk when compared to a single genetic variant assessed alone (Dron & Hegele, 2019; Pereira et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score

Silva,

Resende,

Louro

et al. 2023

Nutrition Bulletin

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Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity‐related genetic risk score and atherogenic risk in Brazilian children. This is a cross‐sectional study conducted in 544 children aged 4–9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity‐related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi‐structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual‐Energy X‐ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity‐related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

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“…Multivariate analysis showed that the GRS is an independent predictor of CHD onset (OR = 1.87, p < 0.0001). The tested GRS added prognostic value to TRFs in all risk subgroups [ 70 ].…”

Section: Modern Models Of Genetic Risk Calculators (2016–2020)mentioning

confidence: 99%

Genetic Risk Score for Coronary Heart Disease: Review

Semaev

Shakhtshneider

2020

JPM

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The present review deals with the stages of creation, methods of calculation, and the use of a genetic risk score for coronary heart disease in various populations. The concept of risk factors is generally recognized on the basis of the results of epidemiological studies in the 20th century; according to this concept, the high prevalence of diseases of the circulatory system is due to lifestyle characteristics and associated risk factors. An important and relevant task for the healthcare system is to identify the population segments most susceptible to cardiovascular diseases (CVDs). The level of individual risk of an unfavorable cardiovascular prognosis is determined by genetic factors in addition to lifestyle factors.

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Additional value of a combined genetic risk score to standard cardiovascular stratification

Cited by 8 publications

References 34 publications

Polygenic modulation of lipoprotein(a)-associated cardiovascular risk

Polygenic modulation of lipoprotein(a)-associated cardiovascular risk

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score

Genetic Risk Score for Coronary Heart Disease: Review

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