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.

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.

Health education interventions to promote health literacy in adults with selected non-communicable diseases living in low-to-middle income countries: A systematic review and meta-analysis.

Rationale, Aims And Objectives: Health illiteracy is an important contributor to the burden of non-communicable diseases (NCDs); in particular in settings where health illiteracy is part of a perpetuating system of risk factors. Interventions that promote health literacy may provide an important tool in the primary and secondary prevention of NCDs. The objective of this systematic review was to evaluate the effectiveness of health literacy interventions on health literacy in the management of patients with selected NCDs living in low-to-middle income countries (LMIC).

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).

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.

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).

No association between common genetic variation in FOXP2 and language impairment in schizophrenia.

The FOXP2 gene is hypothesised to be involved in schizophrenia by affecting speech and language development. Associations between common single nucleotide polymorphisms (SNPs) in FOXP2 and language have been inconsistent. We tested five previously associated SNPs for association with language in the Western Australian Family Study of Schizophrenia (n = 709, including n = 333 with schizophrenia/spectrum disorder) and found no significant associations.

Rediscovering the value of families for psychiatric genetics research.

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.

Whole genome sequencing of 91 multiplex schizophrenia families reveals increased burden of rare, exonic copy number variation in schizophrenia probands and genetic heterogeneity.

The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.

Genetic variants in PPARGC1B and CNTN4 are associated with thromboxane A formation and with cardiovascular event free survival in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

Background And Aims: Elevated urinary 11-dehydro thromboxane B (TxB), a measure of thromboxane A formation in vivo, predicts future atherothrombotic events. To further understand this relationship, the genetic determinants of 11-dehydro TxB and their associations with cardiovascular morbidity were investigated in this study.

Methods: Genome-wide and targeted genetic association studies of urinary 11-dehydro TxB were conducted in 806 Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) participants.

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy).

Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.

Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis.

Exome array analysis suggests an increased variant burden in families with schizophrenia.

The exome array assays rare-but-recurrent, likely deleterious, exonic variants and represents an intermediary between single nucleotide polymorphism (SNP) arrays and sequencing for genetic association studies. Multiplex families with multiple affected individuals may be enriched for disease-associated variants of this class compared to unrelated populations. We present an exome array study of schizophrenia in 99 multiplex families (n=341, including 118 cases) from the Western Australian Family Study of Schizophrenia (WAFSS).

The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia.

Objective: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure.

Integrity of genome-wide genotype data from low passage lymphoblastoid cell lines.

We compared genotype data from the HumanExomeCore Array in peripheral blood mononuclear cells and low passage lymphoblastoid cell lines from the same 24 individuals to test for genotypic errors caused by the Epstein-Barr Virus transformation process. Genotype concordance across the 24 comparisons was 99.57% for unfiltered genotype data, and 99.

Meta-analysis of human methylation data for evidence of sex-specific autosomal patterns.

Background: Several individual studies have suggested that autosomal CpG methylation differs by sex both in terms of individual CpG sites and global autosomal CpG methylation. However, these findings have been inconsistent and plagued by spurious associations due to the cross reactivity of CpG probes on commercial microarrays. We collectively analysed 76 published studies (n = 6,795) for sex-associated differences in both autosomal and sex chromosome CpG sites.

Two further blood pressure loci identified in ion channel genes with a gene-centric approach.

Background: Blood pressure (BP) is highly heritable, but our understanding of the genetic causes underlying variations in BP is incomplete. In this study, we explored whether novel loci associated with BP could be identified using a genecentric approach in 3 community-based cohorts with accurate BP measurements.

Methods And Results: Genotyping of 1857 single nucleotide polymorphisms (SNPs) in 91 ion channel genes was performed in a discovery cohort (n=358).

Genome-wide analysis of blood pressure variability and ischemic stroke.

Background And Purpose: Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke.

Methods: A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available.

Activation of rhodopsin kinase.

The present study confirms our original assertion that peptides corresponding to the C-terminal sequence of rhodopsin are phosphorylated by rhodopsin kinase (RK), but only in the presence of photo-activated rhodopsin [Rho*, which is functionally equivalent to metarhodopsin II (Meta II)]. Under optimized conditions, the extent of peptide phosphorylation reached up to 60% that of Rho*. Rho* phosphorylation began to plateau within 15 min of the initiation of photolysis, whereas the peptide phosphorylation continued linearly for >60 min.