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Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes.

BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants

Exclusive breastfeeding can attenuate body-mass-index increase among genetically susceptible children: A longitudinal study from the ALSPAC cohort.

Recent discoveries from large-scale genome-wide association studies (GWASs) explain a larger proportion of the genetic variability to BMI and obesity. The genetic risk associated with BMI and obesity can be assessed by an obesity-specific genetic risk score (GRS) constructed from genome-wide significant genetic variants. The aim of our study is to examine whether the duration and exclusivity of breastfeeding can attenuate BMI increase during childhood and adolescence due to genetic risks. A total sample of 5,266 children (2,690 boys and 2,576 girls) from the Avon Longitudinal Study of Parents …

Development of a polygenic risk score to improve detection of peripheral artery disease.

INTRODUCTION: Peripheral artery disease (PAD) is a major cause of cardiovascular morbidity and mortality, yet timely diagnosis is elusive. Larger genome-wide association studies (GWAS) have now provided the ability to evaluate whether genetic data, in the form of genome-wide polygenic risk scores (PRS), can help improve our ability to identify patients at high risk of having PAD. METHODS: Using summary statistic data from the largest PAD GWAS from the Million Veteran Program, we developed PRSs with genome data from UK Biobank. We then evaluated the clinical utility of adding the best-performi

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

IMPORTANCE: There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. OBJECTIVES: To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases

Genetically determined telomere length and multiple myeloma risk and outcome.

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been

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… Association between genetic risk score for telomere length and risk of breast cancer. Cancer Causes Control. 2016;27:1219–1228. doi: 10.1007/s10552-016-0800-z. 45. Giaccherini M, et al. Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms. …

Social isolation, loneliness, genetic risk, and incident dementia in people with type 2 diabetes mellitus: A population-based cohort study.

BackgroundSocial isolation and loneliness, two independent constructs of social disengagement, are becoming increasingly recognized factors for dementia risk.ObjectiveWe aimed to investigate whether these two constructs also associate with dementia risk in individuals with type 2 diabetes mellitus (T2DM), which is becoming more prevalent.MethodsThe longitudinal study included 24,986 participants (mean age: 60.0 ± 6.9 years, median follow-up: 12.0 years) with T2DM at baseline from the UK Biobank. Social isolation and loneliness were assessed using self-reported questionnaires. Genetic risk fact

Risk for Mood, Anxiety, and Psychotic Disorders in Individuals at High and Low Genetic Liability for Bipolar Disorder and Major Depression.

IMPORTANCE: The nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum. OBJECTIVE: To better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD). DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted with data for individuals born in Sweden to Swedish parents from 1960 to 1990, with follow-up through December 31, 2018. The data included family genetic risk scores for MD and BD and International Classification …

Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health.

There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background.We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries.We estimated 0.08 (95% CI 0.06-0.11) heritability and identified five loci associated with OSA (p<5.0×10-8): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains

Association of OPG, TNF-α, and IL-1B Gene Variants With Periodontitis in a South African Population.

AIM: This study aimed to investigate candidate single-nucleotide polymorphisms linked to periodontitis susceptibility in a Western Cape cohort, providing insights into population-specific host genetic factors. MATERIALS AND METHODS: This observational case-control study recruited a total of 150 South African participants. Saliva samples were genotyped using the OpenArray QuantStudio 12K Flex qPCR System. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium and tested for associations with clinical variables and disease status using Chi-square tests and logistic regress

Genetic links between female reproductive milestones and major depressive disorder: evidence from a common genetic factor model.

BACKGROUND: Major depressive disorder (MDD) is more prevalent in women and has been linked to female reproductive timing. However, the genetic mechanisms underlying these associations remain unclear. Reproductive milestones are temporally structured and biologically interrelated, suggesting a shared genetic architecture that may influence MDD susceptibility. METHODS: Using large-scale genome-wide association study (GWAS)data, we analyzed five key female reproductive milestones and their genetic relationships with MDD. We applied linkage disequilibrium score regression (LDSC), Genomic Structur

Toward a methodology for evaluating DNA variants in nuclear families.

The genetic underpinnings of most pediatric-cancer cases are unknown. Population-based studies use large sample sizes but have accounted for only a small proportion of the estimated heritability of pediatric cancers. Pedigree-based studies are infeasible for most human populations. One alternative is to collect genetic data from a single nuclear family and use inheritance patterns within the family to filter candidate variants. This approach can be applied to common and rare variants, including those that are private to a given family or to an affected individual. We evaluated this approach us

Prediction of Extraintestinal Manifestations in Inflammatory Bowel Disease Using Clinical and Genetic Variables with Machine Learning in a Latin IBD Group.

Extraintestinal manifestations (EIMs) significantly increase morbidity in inflammatory bowel disease (IBD) patients. In this study, we examined clinical and genetic factors associated with EIMs in 414 Latin IBD patients, utilizing machine learning for predictive modeling. In our IBD group (314 ulcerative colitis (UC) and 100 Crohn's disease (CD) patients), EIM presence was assessed. Clinical differences between patients with and without EIMs were analyzed using Chi-square and Mann-Whitney U tests. Based on the genetic data of 232 patients, we identified variants linked to EIMs, and the polygen

Genetic risk variants for social anxiety.

Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extrav

Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study.

OBJECTIVE: To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between individ … /L [95% CI 1.15-1.42]) and lower HDL concentrations (HR 0.70 per mmol/L [95% CI 0.55-0.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment. CONCLUSIONS: Incre …

Association of regular aerobic exercises and neuromuscular junction variants with incidence of frailty: an analysis of the Chinese Longitudinal Health and Longevity Survey.

BACKGROUND: Candidate genes of neuromuscular junction (NMJ) pathway increased risk of frailty, but the extent and whether can be offset by e … ividuals among them submitted saliva samples. NMJ pathway-related genes were genotyped and weighted genetic risk scores were constructed. RESULTS: During a median follow-up of 3.1 years (19 634 person-years), there were 1345 cases (19.2%) of incident frailty. Persistent aerobic exercises were associated with a 26% lesser frailty risk [adjusted hazard ratio (HR) = 0 …

Interactive effects of genetic liability and combat exposure on risk of alcohol use disorder among US service members.

BACKGROUND: An improved understanding of pathways to alcohol use disorder (AUD) among service members may inform efforts to reduce the substantial impact of AUD on this population. This study examined whether the relationship between a service-related risk factor (combat exposure) and later AUD varied based on individual differences in genetic liability to AUD. METHODS: The sample consisted of 1203 US Army soldiers of genetically determined European ancestry who provided survey and genomic data in the Army STARRS Pre/Post Deployment Study (PPDS; 2012-2014) and follow-up survey data in wave 1

Genetic Susceptibility to NSAID-Related Gastrointestinal Adverse Events in Korean Patients: An Exploratory Genome-Wide Association Study.

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but can cause clinically significant gastrointestinal adverse events (GI-AEs). However, genetic susceptibility to NSAID-related GI toxicity remains insufficiently characterized in East Asian populations. This exploratory study aimed to identify genetic loci associated with grade ≥ 2 NSAID-related GI-AEs in Korean patients treated with commonly used NSAIDs. Methods: We conducted an exploratory genome-wide association study in a multicenter Korean cohort of NSAID-treated patients recruited from four Korean hospi

Genetic risk accentuates dietary effects on hepatic steatosis, inflammation and fibrosis in a population-based cohort.

BACKGROUND & AIMS: Steatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has a differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank. METHODS: We included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-

Chronic migraine: Genetics or environment?

BACKGROUND: The transition from episodic migraine to chronic migraine, migraine chronification, is usually a gradual process, which involves multiple risk factors. To date, studies of the genetic risk factors for chronic migraine have focused primarily on candidate-gene approaches using healthy individuals as controls. AIMS AND METHODS: In this study, we used a large cohort of migraine families and unrelated migraine patients (n > 2200) with supporting genotype and whole-genome sequencing data. We evaluated whether there are any genetic variants, common or rare, with a specific association to

Genetic variation within endolysosomal system is associated with late-onset Alzheimer's disease.

Late-onset Alzheimer's disease is the most common dementia type, yet no treatment exists to stop the neurodegeneration. Evidence from monogenic lysosomal diseases, neuronal pathology and experimental models suggest that autophagic and endolysosomal dysfunction may contribute to neurodegeneration by disrupting the degradation of potentially neurotoxic molecules such as amyloid-β and tau. However, it is uncertain how well the evidence from rare disorders and experimental models capture causal processes in common forms of dementia, including late-onset Alzheimer's disease. For this reason, we set