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Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. T … hese NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an AUC of 0.86. CONCLUSIONS: This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD patients. We have identified multiple novel SNPs associated with CAA/L and related …

Association of Nongenetic Factors With Breast Cancer Risk in Genetically Predisposed Groups of Women in the UK Biobank Cohort.

IMPORTANCE: The association between noninherited factors, including lifestyle factors, and the risk of breast cancer (BC) in women and the association between BC and genetic makeup are only partly characterized. A study using data on current genetic stratification may help in the characterization. OBJECTIVE: To examine the association between healthier lifestyle habits and BC risk in genetically predisposed groups. DESIGN, SETTING, AND PARTICIPANTS: Data from UK Biobank, a prospective cohort comprising 2728 patients with BC and 88 489 women without BC, were analyzed. The data set used for th

Sleep disturbances as risk factors for neurodegeneration later in life.

The relationship between sleep disorders and neurodegeneration is complex and multi-faceted. Using over one million electronic health records (EHRs) from Wales, UK, and Finland, we mined biobank data to identify the relationships between sleep disorders and the subsequent manifestation of neurodegenerative diseases (NDDs) later in life. We then examined how these sleep disorders' severity impacts neurodegeneration risk. Additionally, we investigated how sleep attributed risk may compensate for the lack of genetic risk factors (i.e. a lower polygenic risk score) in NDD manifestation. We found t

Life-course exposure to PM2.5 components and genetic susceptibility on the risk of atrial fibrillation and subsequent heart failure.

AIMS: The life-course joint effects of specific fine particulate matter (PM2.5) components and genetic susceptibility on the progression from atrial fibrillation (AF) to heart failure (HF) remain uncertain. We aimed to investigate these associations for both incident AF and its subsequent progression to HF. METHODS AND RESULTS: In this prospective study of 464 541 UK Biobank participants, we estimated life-course residential exposures to PM2.5 and its key components-including elemental carbon (EC), organic carbon (OC), ammonium (NH₄⁺), nitrate (NO₃⁻), and sulfate (SO₄²⁻)-using a validated spa

Predictive Performance of an Updated Polygenic Risk Score for Age-Related Macular Degeneration.

PURPOSE: A recent genome-wide association study of age-related macular degeneration (AMD) identified new AMD-associated risk variants. These variants now can be incorporated into an updated polygenic risk score (PRS). This study aimed to assess the performance of an updated PRS, PRS2023, in an independent cohort of older individuals with retinal imaging data and to compare performance with an older PRS, PRS2016. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 4175 participants of European ancestry, 70 years of age or older, with genotype and retinal imaging data. METHODS: We used lo

Genome-Wide Polygenic Score and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease: A Nested Case-Control Study.

Genome-wide polygenic scores (GPSs) integrate information from many common DNA variants into a single measure of inherited susceptibility, and can identify individuals who are at substantially elevated risk of developing important common diseases., For coronary artery disease, about 8% of the population can be identified who are at triple the normal risk based on genetic variation alone. Among these high polygenic score individuals, adherence to a healthy lifestyle or use of statins may offset increased inherited risk.,

Communicating Personal Melanoma Polygenic Risk Information: Participants' Experiences of Genetic Counseling in a Community-Based Study.

Personalized polygenic risk information may be used to guide risk-based melanoma prevention and early detection at a population scale, but research on communicating this information is limited. This mixed-methods study aimed to assess the acceptability of a genetic counselor (GC) phone call in communicating polygenic risk information in the Melanoma Genomics Managing Your Risk randomized controlled trial. Participants (n = 509) received personalized melanoma polygenic risk information, an educational booklet on melanoma prevention, and a GC phone call, which was audio-recorded. Participants co

Polygenic Risk Score and Risk Factors for Preeclampsia and Gestational Hypertension.

Preeclampsia and gestational hypertensive disorders (GHD) are common complications of pregnancy that adversely affect maternal and offspring health, often with long-term consequences. High BMI, advanced age, and pre-existing conditions are known risk factors for GHD. Yet, assessing a woman's risk of GHD based on only these characteristics needs to be reevaluated in order to identify at-risk women, facilitate early diagnosis, and implement lifestyle recommendations. This study demonstrates that a risk score developed with machine learning from the case-control genetics dataset can be used as an

Neuroanatomical correlates of genetic risk for obesity in children.

Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, ex

The roles of lifestyle factors and genetic risk in the association between night shift work and cholelithiasis: a prospective cohort study.

BACKGROUND: Night shift work has been associated with adverse health outcomes. Whether night shift work is associated with cholelithiasis remains uncertain, and the roles of genetic risk and lifestyle factors in cholelithiasis risk are unclear. METHODS: We conducted a prospective analysis of 219,810 UK Biobank participants. Cox proportional hazards models were used to estimate the association between night shift work and incident cholelithiasis. Polygenic risk score analyses and causal mediation analyses were performed to investigate the roles of the genetic risk and lifestyle factors in chol

Rare penetrant mutations confer severe risk of common diseases.

UNLABELLED: We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ∼10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unifi

Eating Disorders and Parkinson's Disease-2: Genetic Epidemiology and Shared Genomics.

OBJECTIVE: Individuals with anorexia nervosa (AN) share premorbid traits with Parkinson's Disease (PD) (e.g., anxiety) and exhibit a two-fold relative risk of a reported family history of PD. Published estimates of intra- and inter-disorder genetic architecture were extracted and compared prior to conducting novel analyses to provide evidence for cross-disorder genetic risk. METHODS: National register or meta-analytic familial, twin, and common variant genome-wide studies were searched; estimates and findings were extracted and compared. Novel cross-disorder conditional and conjunctional fals

Genomic structural equation modeling reveals latent phenotypes in the human cortex with distinct genetic architecture.

Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for 34 brain regions recently reported in the ENIGMA cortical GWAS. Genomic SEM uses the empirical genetic covariance estimate

Air Pollution and Incident Cardiovascular Disease: Modification by Genetic Susceptibility and the Mitigating Role of Physical Activity.

BACKGROUND: The interplay and joint effects of air pollution, genetic predisposition, and physical activity (PA) on incident cardiovascular disease (CVD) remain poorly understood. This study aimed to examine the associations between various air pollutants and CVD and assessed potential modification by genetic susceptibility and PA. METHODS: This prospective cohort study included 330 481 UK Biobank participants without baseline CVD. Annual average concentrations of particulate matter <2.5 μm (PM2.5), PM10, PM2.5-10, nitrogen oxides, and nitrogen dioxide were estimated using land-use regression

Аллергические фенотипы и астма в множестве склерозов: эпидемиологические и генетические связи.

Множественный склероз (MS) и аллергические расстройства (AD) классически рассматриваются как иммунологическое различие, и предварительные исследования указывают на потенциальные обратные связи и дублирование генетических факторов. ЦЕЛИ: Сопоставление распространенности астмы и диетических и экологических аллергических фенотипов у людей с MS (PwMS) с нетронутыми мерами контроля, сопоставление распространенности AD с клиническими курсами MS и оценка связей между генетическим риском MS, HLA-DRB1*15:01 и оценкой генетического риска, не связанного с MHC (GRS), и AD в PwMS. Мы проанализировали резул

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) and allergic disorders (ADs) are classically seen as immunologically distinct, and prior studies suggest … MS clinical course, and evaluate associations between MS genetic risk, HLA-DRB1*15:01 and a non-MHC genetic risk score (GRS), and ADs in PwMS. METHODS: We analyzed survey and genotype data from 1542 PwMS and 700 controls from the Accelerated Cure Project. Logistic regression models were adjusted for key confounders. Genetic analyses included 1252 unrelated non-Hisp …

Cardiovascular health, genetic susceptibility, and the risk of ischemic stroke: A large prospective cohort study.

BACKGROUND: Ischemic stroke (IS) remains a major cause of death and disability. We assessed the association between cardiovascular health (CVH), quantified by Life's Essential 8 (LE8), and incident IS, and examined whether polygenic risk score (PRS) modifies this association. METHODS: We studied 234,991 UK Biobank participants with no history of ischemic stroke at baseline (median age 58 years [IQR, 50-64]; range, 37-73), evaluating CVH with the LE8 score, categorized as low (< 50), intermediate (50-79), or high (≥80). Genetic risk was assessed using a GWAS-derived PRS, classified into low (Q

Mapping Gastroesophageal Reflux Disease and Coronary Artery Disease: A Comprehensive Analysis of Multivariable Mendelian Randomization and Shared Genetic Etiology.

AIMS: We employed a robust genetic approach to provide a better understanding of whether Gastroesophageal reflux disease (GERD) contributes to coronary artery disease (CAD) risk from a genetic perspective. METHODS: Multivariable Mendelian Randomization (MVMR) was applied to explore causal links between GERD and CAD using genetic instruments derived from genome-wide association studies (GWAS). The MVMR models were adjusted for key metabolic confounders, including low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), systolic blood pressure (SBP), and glycated hemoglobin (HbA1c).

Effects of polygenic risk for Alzheimer's disease on rate of cognitive decline in normal aging.

Most people's cognitive abilities decline with age, with significant and partly genetically driven, individual differences in rate of change. Although APOE ɛ4 and genetic scores for late-onset Alzheimer's disease (LOAD) have been related to cognitive decline during preclinical stages of dementia, there is limited knowledge concerning genetic factors implied in normal cognitive aging. In the present study, we examined three potential genetic predictors of age-related cognitive decline as follows: (1) the APOE ɛ4 allele, (2) a polygenic score for general cognitive ability (PGS-cog), and (3) a po

Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer's disease.

BACKGROUND: Genetic risk for Alzheimer's disease (AD) can be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the epsilon 4 allele increases the risk of developing late-onset AD but is not a definitive predictor of the disease, or by autosomal dominant mutations (eg, the presenilins), which almost inevitably result in early-onset familial AD. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients. METHODS: Data were compared fro

The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study.

BACKGROUND: The relationship between psychotic disorders and cannabis use is heavily debated. Shared underlying genetic risk is one potential explanation. We investigated the genetic association between psychotic disorders (schizophrenia and bipolar disorder) and cannabis phenotypes (lifetime cannabis use and cannabis use disorder). METHODS: We used genome-wide association summary statistics from individuals with European ancestry from the Psychiatric Genomics Consortium, UK Biobank, and International Cannabis Consortium. We estimated heritability, polygenicity, and discoverability of each ph