Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction.

Unlabelled: A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

The Influence of DNA Repair Genes and Prenatal Tobacco Exposure on Risk of Childhood Acute Lymphoblastic Leukemia: A Gene-Environment Interaction Study.

Background: Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicologic profile as a DNA-damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL.

Impact of childhood exposure to traffic related air pollution on adult cardiometabolic health: Exploring the role of perceived stress.

Background: Little is known about how childhood exposure to traffic-related air pollution (TRAP) and stress interact to affect adults' cardiometabolic health. We examined this interaction and assessed the impact of over 10 years of childhood TRAP exposure on cardiometabolic health.

Methods: From 2018 to 2023, 313 young adults from the Southern California Children's Health Study were enrolled in a follow-up assessment.

Children's Health in London and Luton (CHILL) cohort: a 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children's travel to school.

Background: The Ultra-Low Emission Zone (ULEZ), introduced in Central London in April 2019, aims to enhance air quality and improve public health. The Children's Health in London and Luton (CHILL) study evaluates the impact of the ULEZ on children's health. This analysis focuses on the one-year impacts on the shift towards active travel to school.

Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences.

Background: Air pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex.

Methods: We investigate sex-stratified effects of annual exposure to fine particulate matter (PM), nitrogen dioxide (NO), and ozone (O) at ages 9-10 years on longitudinal patterns of white matter microstructure over a 2-year period.

Association Between Cardiovascular Health and Subclinical Atherosclerosis Among Young Adults Using the American Heart Association's "Life's Essential 8" Metrics.

Background: This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults.

Methods And Results: This cross-sectional study included 240 young adults (age 24.2±1.

Does socioeconomic and environmental burden affect vulnerability to extreme air pollution and heat? A case-crossover study of mortality in California.

Background: Extreme heat and air pollution is associated with increased mortality. Recent evidence suggests the combined effects of both is greater than the effects of each individual exposure. Low neighborhood socioeconomic status ("socioeconomic burden") has also been associated with increased exposure and vulnerability to both heat and air pollution.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

An approach to identify gene-environment interactions and reveal new biological insight in complex traits.

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.