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Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors.

ABSTRACT: Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors present the current state of knowledge on the potential genetic links between psoriasis and cardiovascular risk factors. The understanding of the processes linking psoriasis with cardiovascular risk factors can lead to improvement of psoriasis management in the future.

SUBMITTER: Purzycka-Bohdan D

PROVIDER: S-EPMC8396451 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors.

Purzycka-Bohdan Dorota D Kisielnicka Anna A Bohdan Michał M Szczerkowska-Dobosz Aneta A Sobalska-Kwapis Marta M Nedoszytko Bogusław B Nowicki Roman J RJ

International journal of molecular sciences 20210823 16

Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors presen ...[more]

PMID: 34445769

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Project description:Cardiovascular (CV)- and lifestyle-associated risk factors (RFs) are increasingly recognized as important for Alzheimer's disease (AD) pathogenesis. Beyond the ε4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV-associated genes also increase risk for AD. Using large genome-wide association studies and validated tools to quantify genetic overlap, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with AD and one or more CV-associated RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist hip ratio (WHR), total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL). In fold enrichment plots, we observed robust genetic enrichment in AD as a function of plasma lipids (TG, TC, LDL, and HDL); we found minimal AD genetic enrichment conditional on BMI, T2D, CAD, and WHR. Beyond APOE, at conjunction FDR < 0.05 we identified 90 SNPs on 19 different chromosomes that were jointly associated with AD and CV-associated outcomes. In meta-analyses across three independent cohorts, we found four novel loci within MBLAC1 (chromosome 7, meta-p = 1.44 × 10-9), MINK1 (chromosome 17, meta-p = 1.98 × 10-7) and two chromosome 11 SNPs within the MTCH2/SPI1 region (closest gene = DDB2, meta-p = 7.01 × 10-7 and closest gene = MYBPC3, meta-p = 5.62 × 10-8). In a large 'AD-by-proxy' cohort from the UK Biobank, we replicated three of the four novel AD/CV pleiotropic SNPs, namely variants within MINK1, MBLAC1, and DDB2. Expression of MBLAC1, SPI1, MINK1 and DDB2 was differentially altered within postmortem AD brains. Beyond APOE, we show that the polygenic component of AD is enriched for lipid-associated RFs. We pinpoint a subset of cardiovascular-associated genes that strongly increase the risk for AD. Our collective findings support a disease model in which cardiovascular biology is integral to the development of clinical AD in a subset of individuals.

Project description:ObjectivesPsoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.MethodsGenome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.ResultsWe identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP = 0.63), which was similar to the heritability of PsC (h2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.ConclusionKey biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Project description:Background: Cardiovascular disease (CVD) is a complex disease resulting from multiscale risk factors including genetics, age, and psychosocial factors (PSFs) such as depression and social isolation. However, previous research has lacked in operationalizing multiscale risk factors to determine individual and interactive associations over the life course. Therefore, this study aimed to evaluate individual and interactive associations of multiscale risk factors for CVD outcomes including genetics and PSFs at middle and older-aged stages of the life course. Methods: Baseline data from the Canadian Longitudinal Study on Aging (CLSA; n = 9,892 with genome-wide genotyping data) was used for this investigation. A 39 single nucleotide polymorphism polygenic risk score (PRS) for CVD was constructed. PSFs consisted of: (1) Depressive symptoms categorized into: "none" (Group 1, reference), "current" (Group 2), "clinical depression with no current symptoms" (Group 3), and "potential, recurrent depression" (Group 4); and (2) Social isolation index as a binary variable comprised of marital status, living arrangements, retirement status, contacts, and social participation. Heart-related disorders (HRD: myocardial infarction, angina and heart disease) was the primary outcome of interest and peripheral/vascular-related disorders (PVRD: stroke, peripheral vascular disease and hypertension) was the secondary outcome. Multivariable logistic regression models adjusted for socio-demographic factors were conducted stratified by age group (middle-aged: 45-69 years, older-aged: ≥70 years). Results: PRS was associated with HRD among middle- and older-aged participants [OR (95% confidence interval)] [1.06 (1.03-1.08), 1.06 (1.03-1.08), respectively]. Most depressive symptoms groups compared to the reference associated with HRD and PVRD, but only Group 4 associated with PVRD among older-aged [1.69 (1.08-2.64)]. Social isolation was associated with only PVRD among middle-aged [1.84 (1.04-3.26)]; however, socially isolated CLSA participants were underrepresented in the genotyped cohort (1.2%). No significant PRS*PSFs interactions were observed. Conclusions: Genetics and PSFs are independently associated with CVD. Varying observations across age groups underscores the need to advance research on multiscale risk factors operating both at a given point in time and over the life course. Future cohort studies may benefit from use of mobile assessment units to enable better reach to socially isolated participants for collection of biospecimens.

Dataset Information

Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors.

Publications

Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors.

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