The Causal Effect of Adult Height on Late-Life Handgrip Strength: The Singapore Chinese Health Study.

Background: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias.

Methods: We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore.

Plasma fatty acid esters of hydroxy fatty acids and surrogate fatty acid esters of hydroxy fatty acids hydrolysis activity in children with or without obesity and in adults with or without coronary artery disease.

Aim: Fatty acid esters of hydroxy fatty acids (FAHFA) are a class of bioactive lipids with anti-inflammatory, antidiabetic and cardioprotective properties. FAHFA hydrolysis into its fatty acid (FA) and hydroxy fatty acid (HFA) constituents can affect the bioavailability of FAHFA and its subsequent biological effects. We aimed to investigate FAHFA levels and FAHFA hydrolysis activity in children with or without obesity, and in adults with or without coronary artery disease (CAD).

Disruption of Aldehyde Dehydrogenase 2 protects against bacterial infection.

Unlabelled: The (rs671) allele is one of the most common genetic mutations in humans, yet the positive evolutionary selective pressure to maintain this mutation is unknown, despite its association with adverse health outcomes. ALDH2 is responsible for the detoxification of metabolically produced aldehydes, including lipid-peroxidation end products derived from inflammation. Here, we demonstrate that host-derived aldehydes 4-hydroxynonenal (4HNE), malondialdehyde (MDA), and formaldehyde (FA), all of which are metabolized by ALDH2, are directly toxic to the bacterial pathogens and at physiological levels.

A five-safes approach to a secure and scalable genomics data repository.

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud.

Increased BMI and late-life mobility dysfunction; overlap of genetic effects in brain regions.

Background: How obesity earlier in life impacts upon mobility dysfunctions in late life is not well understood. Pernicious effects of excess weight on the musculoskeletal system and mobility dysfunctions are well-recognized. However, increasingly more data support the link of obesity to overall motor defects that are regulated in the brain.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

Trans-interaction of risk loci 6p24.1 and 10q11.21 is associated with endothelial damage in coronary artery disease.

Background And Aims: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1.

The association of genetic susceptibility to smoking with cardiovascular disease mortality and the benefits of adhering to a DASH diet: The Singapore Chinese Health Study.

Background: Understanding the genetic predisposition to cardiovascular disease (CVD) may help to improve clinical intervention strategies. Lifestyle factors, such as diet, may differ among ethnic groups and may, in turn, modify individuals' risks to diseases.

Objectives: We examined the genetic predisposition to ever smoking in relation to CVD mortality and assessed whether such an association could be modified by dietary intake.

NAFLD polygenic risk score and risk of hepatocellular carcinoma in an East Asian population.

It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC-PRS) derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population-level data of this risk in Asian populations are lacking.

Interaction between cigarette smoking and genetic polymorphisms on the associations with age of natural menopause and reproductive lifespan: the Singapore Chinese Health Study.

Study Question: Are there genetic variants that interact with smoking to reduce reproductive lifespan in East-Asian women?

Summary Answer: Our study corroborates several recently identified genetic loci associated with reproductive lifespan and highlights specific genetic predispositions that may interact with smoking status to adversely affect reproductive lifespan in East-Asian women.

What Is Known Already: Epidemiological data as well as evaluations on genetic predisposition to smoke indicate on the importance of smoking in adverse effects on reproductive lifespan in women. However, there are no previous smoking and gene interaction studies for reproductive traits in East-Asian women.

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

Aims: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.

Methods And Results: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.

The power of genetic diversity in genome-wide association studies of lipids.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.

Lipoprotein(a) as predictor of coronary artery disease and myocardial infarction in a multi-ethnic Asian population.

Background And Aims: The role of Lp(a) in multi-ethnic Asian populations with coronary artery disease (CAD) has not been well established. The aims of this study were (i) to investigate whether Lp(a) is a predictor of CAD, and (ii) amongst patients with CAD, to ascertain whether Lp(a) is a predictor of acute myocardial infarction (AMI) and severity of CAD.

Methods: We compared three cardiovascular phenotypes from patients recruited at coronary angiography.

Androgen-dependent tissue factor pathway inhibitor regulating protein: a review of its peripheral actions and association with cardiometabolic diseases.

The first genome-wide association study on coronary artery disease (CAD) in the Han Chinese population identified C6orf105 as a susceptibility gene. The C6orf105 gene was later found to encode for a protein that regulates tissue factor pathway inhibitor (TFPI) expression in endothelial cells in an androgen-dependent manner, and the novel protein was thus termed androgen-dependent TFPI-regulating protein (ADTRP). Since the identification of ADTRP, there have been several studies associating genetic variants on the ADTRP gene with CAD risk, as well as research providing mechanistic insights on this novel protein and its functional role.

The association of genetically determined serum glycine with cardiovascular risk in East Asians.

Background And Aims: Glycine is involved in a wide range of metabolic pathways and increased circulating glycine is associated with reduced risk of cardio-metabolic diseases in Europeans but the genetic association between circulating glycine and cardiovascular risk is largely unknown in East Asians.

Methods And Results: We conducted a genome-wide association study (GWAS) in Singaporean Chinese participants and investigated if genetically determined serum glycine were associated with incident coronary artery disease (CAD) (711 cases and 1,246 controls), cardiovascular death (1,886 cases and 21,707 controls) and angiographic CAD severity (as determined by the Modified Gensini score, N = 1,138).

Conclusion: Our study, a first in East Asians, suggest a protective role of glycine against CAD.

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

Aims: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.

Methods And Results: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000).

Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population.

Background: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging.