Sex-related differences in single nucleotide polymorphisms associated with dyslipidemia in a Korean population

Lee, Gyeonghee; Jeon, Hye Kyung; Yoo, Hae Young

doi:10.1186/s12944-022-01736-5

Cited by 7 publications

(4 citation statements)

References 58 publications

(59 reference statements)

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“…Gene–alcohol–drinking interaction was shown on blood glucose level and type-II diabetes (T2D) via one PRS-based study [ 32 ] and two genetic-variant-level studies [ 33 , 34 ]. Additionally, gene–sex interaction effects have been reported for traits such as APOB [ 35 , 36 ], height [ 37 ], total cholesterol level [ 35 , 38 , 39 ], height [ 40 , 41 ], psychiatric health [ 42 , 43 ], and T2D [ 44 , 45 ], all of which were exclusively detected by LDER-GE.…”

Section: Resultsmentioning

confidence: 99%

LDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information

Dong,

Jiang,

et al. 2024

Briefings in Bioinformatics

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Gene–environment (GE) interactions are essential in understanding human complex traits. Identifying these interactions is necessary for deciphering the biological basis of such traits. In this study, we review state-of-art methods for estimating the proportion of phenotypic variance explained by genome-wide GE interactions and introduce a novel statistical method Linkage-Disequilibrium Eigenvalue Regression for Gene–Environment interactions (LDER-GE). LDER-GE improves the accuracy of estimating the phenotypic variance component explained by genome-wide GE interactions using large-scale biobank association summary statistics. LDER-GE leverages the complete Linkage Disequilibrium (LD) matrix, as opposed to only the diagonal squared LD matrix utilized by LDSC (Linkage Disequilibrium Score)-based methods. Our extensive simulation studies demonstrate that LDER-GE performs better than LDSC-based approaches by enhancing statistical efficiency by ~23%. This improvement is equivalent to a sample size increase of around 51%. Additionally, LDER-GE effectively controls type-I error rate and produces unbiased results. We conducted an analysis using UK Biobank data, comprising 307 259 unrelated European-Ancestry subjects and 966 766 variants, across 217 environmental covariate-phenotype (E-Y) pairs. LDER-GE identified 34 significant E-Y pairs while LDSC-based method only identified 23 significant E-Y pairs with 22 overlapped with LDER-GE. Furthermore, we employed LDER-GE to estimate the aggregated variance component attributed to multiple GE interactions, leading to an increase in the explained phenotypic variance with GE interactions compared to considering main genetic effects only. Our results suggest the importance of impacts of GE interactions on human complex traits.

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Section: Resultsmentioning

confidence: 99%

LDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information

Dong,

Jiang,

et al. 2024

Briefings in Bioinformatics

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“…For instance, higher HDL-C levels in women correlate with greater expression of the lysine demethylase 6A gene, the silencing of which reduces apoA-I expression and HDL-C levels [79]. In addition, certain sex-specific single nucleotide polymorphisms in CETP and apoA-V genes are related to dyslipidemia [80].…”

Section: Role Of Geneticsmentioning

confidence: 99%

Sex aspects in lipoprotein metabolism, dyslipidemia, and lipid-lowering therapy: A comprehensive review

Zimodro,

Mucha,

Berthold

et al. 2024

Preprint

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Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

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“…Several studies have discovered that males and females show dissimilar lipid metabolism, such as a greater percentage of men than women with elevated TG concentration in the blood, or the tendency for middle-aged women to have higher levels of HDL-C than men [10][11][12]. Interestingly, a single nucleotide polymorphism (SNP) in APOA5 was associated with dyslipidemia only in male subjects [13].…”

Section: Introductionmentioning

confidence: 99%

Associations between the Genetic Heritability of Dyslipidemia and Dietary Patterns in Korean Adults Based on Sex Differences

Kim,

Jeon,

Lee

et al. 2023

Nutrients

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Dyslipidemia can be defined as an abnormality in serum lipid levels that is substantially linked to genetic variations and lifestyle factors, such as diet patterns, and has distinct sex-specific characteristics. We aimed to elucidate the genetic impact of dyslipidemia according to sex and explore the associations between genetic variants and dietary patterns in large-scale population-based cohorts. After performing genome-wide association studies (GWASs) in male, female, and entire cohorts, significant single nucleotide polymorphisms (SNPs) were identified in the three groups, and genetic risk scores (GRSs) were calculated by summing the risk alleles from the selected SNPs. After adjusting for confounding variables, the risk of dyslipidemia was 2.013-fold and 2.535-fold higher in the 3rd quartile GRS group in the male and female cohorts, respectively, than in the 1st quartile GRS group. While instant noodle and soft drink intake were significantly associated with GRS related to hyperlipidemia in male cohorts, coffee consumption was substantially related to GRS related to hyperlipidemia in female cohorts. Considering the influence of genetic factors and dietary patterns, the findings of this study suggest the potential for implementing sex-specific strategic interventions to avoid dyslipidemia.

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Sex-related differences in single nucleotide polymorphisms associated with dyslipidemia in a Korean population

Cited by 7 publications

References 58 publications

LDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information

LDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information

Sex aspects in lipoprotein metabolism, dyslipidemia, and lipid-lowering therapy: A comprehensive review

Associations between the Genetic Heritability of Dyslipidemia and Dietary Patterns in Korean Adults Based on Sex Differences

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