Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention.

Background: Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies.

Objectives: This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS.

A lipidomic based metabolic age score captures cardiometabolic risk independent of chronological age.

Background: Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual's overall metabolic health.

Methods: Utilising comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,833, including 6630 males, 8203 females), we employed different machine learning models, to predict age, and calculated metabolic age scores (mAge). Furthermore, we defined the difference between mAge and age, termed mAgeΔ, which allow us to identify individuals sharing similar age but differing in their metabolic health status.

Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study.

Background: Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle.

Methods: We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men).

Genomic variation associated with cardiovascular disease progression following preeclampsia: a systematic review.

Background: Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE.

Interactions between the lipidome and genetic and environmental factors in autism.

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster.

A variant in the fibronectin (FN1) gene, rs1250229-T, is associated with decreased risk of coronary artery disease in familial hypercholesterolaemia.

Background: Increased risk of coronary artery disease (CAD) in familial hypercholesterolaemia (FH) is modified by factors beyond defects in the low-density lipoprotein receptor pathway. The rs1250229-T single nucleotide polymorphism (SNP) in the FN1 gene is associated with CAD in genome-wide association studies and is in linkage disequilibrium with another SNP (rs1250259-T) in FN1 that is associated with decrease fibronectin secretion.

Objective: We investigated whether rs1250229-T was also associated with prevalent CAD in patients with genetically confirmed FH.

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts.

Cascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a).

Objective: Elevated lipoprotein(a) [Lp(a)] is a common inherited condition associated with cardiovascular disease. This study investigated whether cascade testing for Lp(a) was effective in detecting new cases of elevated Lp(a) in families.

Methods: Relatives from adult probands with Lp(a) concentration ≥100 mg/dL were tested for elevated Lp(a) (≥50 mg/dL) via a cascade testing program in a tertiary hospital setting.

Evaluation of epigenetic age calculators between preeclampsia and normotensive pregnancies in an Australian cohort.

Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases. The associations between maternal DNA methylation age and preeclampsia (PE) have not been fully assessed. The aim of this study was to examine if increased maternal DNA methylation age (DNAmAge) was shown to be accelerated in women with PE when compared to women who had normotensive pregnancies.

APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.

Introduction: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood.

Methods: We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species.

Cascade testing for elevated lipoprotein(a) in relatives of probands with familial hypercholesterolaemia and elevated lipoprotein(a).

Background And Aims: Familial hypercholesterolaemia (FH) and elevated plasma lipoprotein(a) [Lp(a)] are inherited conditions independently associated with atherosclerotic cardiovascular disease. This study investigated the detection of new cases of elevated Lp(a) during cascade testing of relatives of probands with a definite diagnosis of FH and elevated Lp(a) (≥50 mg/dL).

Methods: Relatives from 62 adult probands were tested for FH genetically and for elevated Lp(a) using an immunoassay.

A Methylome and Transcriptome Analysis of Normal Human Scar Cells Reveals a Role for FOXF2 in Scar Maintenance.

Scars are maintained for life and increase in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scars. In this study, we combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance.

Is Mammographic Breast Density an Endophenotype for Breast Cancer?

Mammographic breast density (MBD) is a strong and highly heritable predictor of breast cancer risk and a biomarker for the disease. This study systematically assesses MBD as an endophenotype for breast cancer-a quantitative trait that is heritable and genetically correlated with disease risk. Using data from the family-based kConFab Study and the 1994/1995 cross-sectional Busselton Health Study, participants were divided into three status groups-cases, relatives of cases and controls.

Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits.

Autism spectrum disorders are complex, with a strong genetic basis. Genetic research in autism spectrum disorders is limited by the fact that these disorders are largely heterogeneous so that patients are variable in their clinical presentations. To address this limitation, we investigated the genetics of individual dimensions of the autism spectrum disorder phenotypes, or autistic-like traits.

Correction: High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies.

[This corrects the article DOI: 10.1371/journal.pbio.

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies.

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level.

Association of Known Melanoma Risk Factors with Primary Melanoma of the Scalp and Neck.

Background: Scalp and neck (SN) melanoma confers a worse prognosis than melanoma of other sites but little is known about its determinants. We aimed to identify associations between SN melanoma and known risk genes, phenotypic traits, and sun exposure patterns.

Methods: Participants were cases from the Western Australian Melanoma Health Study ( = 1,200) and the Genes, Environment, and Melanoma Study ( = 3,280).

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars.

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample.

Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study.

CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes.

A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia: enhancing the precision of risk assessment.

Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD); however, risk prediction and stratification remain a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk. The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation-positive (n = 251) and mutation-negative (n = 560) FH.

Familial and non-familial risk factors associated with incidence of colorectal cancer in young and middle-aged persons in Western Australia.

Aims: The aim of this study was to examine factors including family history, medical history and comorbidities associated with the risk of colorectal cancer (CRC) in young (18-49 years) and middle-age (50-69 years) individuals.

Methods: State records were used to identify individuals born in Western Australia between 1945 and 1996, and their first-degree relatives. Individuals in the cohort and their relatives were linked to State cancer registry, hospital and mortality data to identify diagnoses of CRC and other risk factors.

Familial and non-familial risk factors associated with colorectal cancer survival in young and middle-aged patients.

Background: Survival following colorectal cancer (CRC) survival may be influenced by a number of factors including family history, individual medical history, and comorbidities. The impact of these factors may vary based on the patient's age.

Methods: The study cohort consisted of individuals born in Western Australia between 1945 and 1996, who had been diagnosed with CRC prior to 2015 (n = 3220).