An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease.

Background: Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.

Results: We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system).

Project TENDR: Targeting Environmental Neuro-Developmental Risks The TENDR Consensus Statement.

Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented.

Prenatal Use of Acetaminophen and Child IQ: A Danish Cohort Study.

Background: Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy, and recently has been linked to hyperactivity and behavioral problems in children. We examine whether prenatal use of acetaminophen affects children's intelligence quotient (IQ).

Methods: We studied 1,491 mothers and children enrolled in the Danish National Birth Cohort (DNBC; 1996-2002).

Part 3. Modeling of Multipollutant Profiles and Spatially Varying Health Effects with Applications to Indicators of Adverse Birth Outcomes.

The highly intercorrelated nature of air pollutants makes it difficult to examine their combined effects on health. As such, epidemiological studies have traditionally focused on single-pollutant models that use regression-based techniques to examine the marginal association between a pollutant and a health outcome. These relatively simple, additive models are useful for discerning the effect of a single pollutant on a health outcome with all other pollutants held to fixed values.

Menopause accelerates biological aging.

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790).

Identification of genetic modifiers of age-at-onset for familial Parkinson's disease.

Parkinson's disease (PD) is the most common cause of neurodegenerative movement disorder and the second most common cause of dementia. Genes are thought to have a stronger effect on age-at-onset of PD than on risk, yet there has been a phenomenal success in identifying risk loci but not age-at-onset modifiers. We conducted a genome-wide study for age-at-onset.

Identification of Effects of Regulatory Actions on Air Quality in Goods Movement Corridors in California.

Few studies have assessed the impact of regulatory actions on air quality improvement through a comprehensive monitoring effort. In this study, we designed saturation sampling of nitrogen oxides (NOX) for the counties of Los Angeles and Alameda (San Francisco Bay) before (2003-2007) and after (2008-2013) implementation of goods movement actions in California. We further separated the research regions into three location categories, including goods movement corridors (GMCs), nongoods movement corridors (NGMCs), and control areas (CTRLs).

Synergistic effects of air pollution and psychosocial stressors on adolescent lung function.

Research on synergism of stress and air pollution on adolescent lung function is uncommon. Our study found statistically significant synergism between select psychosocial stressors and air pollution on the lung function of adolescents.

Lifetime occupational and leisure time physical activity and risk of Parkinson's disease.

Introduction: While regular exercise has been shown to alleviate the motor symptoms of Parkinson's disease (PD), it remains unclear whether a physically active lifestyle may prevent PD.

Methods: To examine physical activities across the lifespan and risk of PD, we relied on data from a population-based case-control study that enrolled 357 incident PD cases and 341 controls. We assessed physical activity levels via self-report of (1) overall physical activity (PA) over 4 age periods; (2) competitive sports; and (3) occupational histories.

Psychosocial stressors and lung function in youth ages 10-17: an examination by stressor, age and gender.

Background: Research on the impact of psychosocial stressors on child and adolescent lung function is uncommon, and has primarily relied either on parents' own stress measures or parent-reported stressors the child experienced, which may be a poor proxy for perceived stress in older children and adolescents.

Methods: We performed multivariate linear regression of spirometry measures (FVC, FEV1 and FEF25-75) and psychosocial stressors in 584 adolescents in the Los Angeles Family and Neighborhood Survey. We examined family conflict, unsafe neighborhood or school, and the absence of a father in models stratified by gender, adjusting for PM2.

A connectionist modeling study of the neural mechanisms underlying pain's ability to reorient attention.

Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work.

Risk of Childhood Cancer by Maternal Birthplace: A Test of the Hispanic Paradox.

Importance: The Hispanic epidemiologic paradox is the phenomenon that non-US-born Hispanic mothers who immigrate to the United States have better pregnancy outcomes than their US-born counterparts. It is unknown whether this advantage extends to childhood cancer risk.

Objective: To determine whether the risk for childhood cancers among Hispanic children varies by maternal birthplace.

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

Background: Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD.

Objective: Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients.

The Influence of Pre-natal Supplement Initiation on Preterm Birth Among Majority Hispanic Women in Los Angeles County: The Role of Nativity.

Objectives Despite being encouraged to take pre-natal supplements, suboptimal micronutrient intake is common in pregnancy, especially among Hispanic women. In this study, we assessed whether initiation and timing of pre-natal vitamin use influences the risk of preterm birth. Methods Women who gave birth to singletons in 2003 in Los Angeles County, California, were enrolled into a population-based case-control study.

Smoking in pregnancy and risk of cancer among young children: A population-based study.

Smoking during pregnancy is a plausible risk factor for childhood cancer, yet previous studies have yielded conflicting results, and few prospective studies have been published. Data on maternal smoking were obtained from California birth certificates. We linked California birth certificates (births 2007-2011) with California Cancer Registry records for childhood cancer cases (diagnosed January 2007-September 2013) that were ages 5 or younger at diagnosis (N cases = 2,021).

Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children's Oncology Group.

Background: Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma.

Methods: Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group.

Multi-pollutant exposure profiles associated with term low birth weight in Los Angeles County.

Research indicates that multiple outdoor air pollutants and adverse neighborhood conditions are spatially correlated. Yet health risks associated with concurrent exposure to air pollution mixtures and clustered neighborhood factors remain underexplored. Statistical models to assess the health effects from pollutant mixtures remain limited, due to problems of collinearity between pollutants and area-level covariates, and increases in covariate dimensionality.

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease.

At the start of the postgenomics era, most Parkinson's disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case-control study of incident PD in central California.

Medical Record Review to Differentiate between Idiopathic Parkinson's Disease and Parkinsonism: A Danish Record Linkage Study with 10 Years of Follow-Up.

Background. The electronic medical records provide new and unprecedented opportunities for large population-based and clinical studies if valid and reliable diagnoses can be obtained, to determine what information is needed to distinguish idiopathic PD from Parkinsonism in electronic medical records. Methods.

Editor's Choice-Medically managed patients with non-ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease.

Background: Medically managed individuals represent a high-risk group among patients with non-ST-elevation acute myocardial infarction (NSTE-AMI). We hypothesized that prognosis in this group is heterogeneous, depending on whether medical management was decided with or without coronary angiography (CAG).

Methods: Using data from the French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction (FAST-MI), we analysed data from 798 patients with NSTE-AMI who were medically managed (i.

Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study.

Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996-2002) for average 12.

Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients.

It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging ("epigenetic clock") to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts.

In Utero and Early-Life Exposure to Ambient Air Toxics and Childhood Brain Tumors: A Population-Based Case-Control Study in California, USA.

Background: Little is known about the influence of environmental factors on the etiology of childhood brain tumors.

Objectives: We examined risks for brain tumors in children after prenatal and infant exposure to monitored ambient air toxics.

Methods: We ascertained all cases of medulloblastoma, central nervous system primitive neuroectodermal tumor (PNET), and astrocytoma before 6 years of age diagnosed in 1990-2007 from the California Cancer Registry and selected controls randomly from birth rolls matched by birth year.

A case-control study of sporadic retinoblastoma in relation to maternal health conditions and reproductive factors: a report from the Children's Oncology group.

Background: The early age at retinoblastoma occurrence, the most common eye malignancy in childhood, suggests that perinatal factors may contribute to its etiology.

Methods: In a large multicenter study of non-familial retinoblastoma, we conducted structured interviews with the parents of 280 cases and 146 controls to elicit information on health during the perinatal period. We used unconditional logistic regression to assess associations between retinoblastoma and parental fertility treatment, birth control use in the year prior to pregnancy, maternal health conditions and the use of prescription medications during pregnancy, and whether mothers breastfed the index child.