Novel genetic loci underlying human intracranial volume identified through genome-wide association.

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals.

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent.

Nonlinear associations between plasma cholesterol levels and neuropsychological function.

Objective: Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery.

Method: Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease.

Lifetime Cocaine and Opiate Use and Chronic Kidney Disease.

Background: More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with reduced kidney function, albuminuria and rapid kidney function decline among urban-dwelling adults.

Methods: Our prospective cohort included 2,286 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants who were community-dwelling adults residing in Baltimore, MD.

Racial differences in microRNA and gene expression in hypertensive women.

Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension.

Association between Race, Household Income and Grip Strength in Middle- and Older-Aged Adults.

Background: Poor grip strength is an indicator of frailty and a precursor to functional limitations. Although poor grip strength is more prevalent in older disabled African American women, little is known about the association between race and poverty-related disparities and grip strength in middle-aged men and women.

Methods: We examined the cross-sectional relationship between race, socioeconomic status as assessed by household income, and hand grip strength in men and women in the Healthy Aging in Neighborhoods of Diversity across the Life Span study.

Dietary Magnesium and Kidney Function Decline: The Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

Background: Prior studies suggest that certain aspects of the diet related to magnesium intake, such as dietary acid load, protein intake and dietary patterns rich in fruits and vegetables, may impact kidney disease risk. We hypothesized that lower dietary magnesium intake would be prospectively associated with more rapid kidney function decline.

Methods: Among participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.

Dietary Habits and Risk of Kidney Function Decline in an Urban Population.

Objective: Explore the association between following a Dietary Approaches to Stop Hypertension (DASH)-accordant diet and kidney end points among urban adults.

Design: Prospective cohort study.

Setting: Healthy Aging in Neighborhoods of Diversity across the Life Span study.

Racial disparities in adult all-cause and cause-specific mortality among us adults: mediating and moderating factors.

Background: Studies uncovering factors beyond socio-economic status (SES) that would explain racial and ethnic disparities in mortality are scarce.

Methods: Using prospective cohort data from the Third National Health and Nutrition Examination Survey (NHANES III), we examined all-cause and cause-specific mortality disparities by race, mediation through key factors and moderation by age (20-49 vs. 50+), sex and poverty status.

Indicators of subjective social status: Differential associations across race and sex.

Background: Subjective social status (SSS), or perception of rank on the social hierarchy, is an important indicator of various health outcomes. However, the psychosocial influences on this construct are unclear, and how these influences vary across different sociodemographic groups is poorly understood.

Methods: Participants were 2077 African-American and Whites (M age=47.

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults.

Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex.

Relationship of Physical Intimate Partner Violence with Mental Health Diagnoses in the Nationwide Emergency Department Sample.

Objectives: We examined associations of physical intimate partner violence (PIPV) with selected mental health disorders using a nationally representative sample of emergency department (ED) discharges corresponding to men and women (18-64 years) from the 2010 Nationwide Emergency Department Sample.

Methods: PIPV was determined using International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) external cause of injury code E967.3 (battering by spouse or partner).

Sex, Race, and Socioeconomic Disparities in Patients With Aortic Stenosis (from a Nationwide Inpatient Sample).

Aortic stenosis (AS) is the third most prevalent cardiovascular disease following hypertension and coronary artery disease. The primary objective of this cross-sectional study is to examine gender, racial, and socioeconomic disparities in AS-related health care utilization in patients aged ≥50 years using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. AS was identified among inpatient discharges with International Classification of Diseases, Ninth Revision, Clinical Modification, code 424.

Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases.

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies.

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals.

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV).

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants.

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif.

Race Differences in Diet Quality of Urban Food-Insecure Blacks and Whites Reveals Resiliency in Blacks.

Introduction: Evidence from epidemiological studies shows a link between food insecurity and diet intake or quality. However, the moderating effect of race in this relation has not yet been studied.

Methods: Food insecurity (USDA Food Security Module) and diet quality (Healthy Eating Index-2010; HEI) were measured in 1741 participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study.

Diet quality and cognitive function in an urban sample: findings from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study.

Objective: Poor diet quality contributes to morbidity, including poor brain health outcomes such as cognitive decline and dementia. African Americans and individuals living in poverty may be at greater risk for cognitive decrements from poor diet quality.

Design: Cross-sectional.

Race, Neighborhood Economic Status, Income Inequality and Mortality.

Mortality rates in the United States vary based on race, individual economic status and neighborhood. Correlations among these variables in most urban areas have limited what conclusions can be drawn from existing research. Our study employs a unique factorial design of race, sex, age and individual poverty status, measuring time to death as an objective measure of health, and including both neighborhood economic status and income inequality for a sample of middle-aged urban-dwelling adults (N = 3675).

Alternative Pathway Analyses Indicate Bidirectional Relations between Depressive Symptoms, Diet Quality, and Central Adiposity in a Sample of Urban US Adults.

Background: Temporality between socioeconomic status (SES), depressive symptoms (DS), dietary quality (DQ), and central adiposity (CA) is underexplored.

Objectives: Alternative pathways linking SES to DQ, DS, and CA were tested and models compared, stratified by race and sex.

Methods: With the use of data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (baseline age: 30-64 y; 2 visits; mean follow-up: 4.

Serum Uric Acid and Its Association with Longitudinal Cognitive Change Among Urban Adults.

Uric acid, a waste metabolite among humans, was linked to various cognitive outcomes. We describe sex and age-group specific associations of baseline serum uric acid (SUAbase) and significant change in SUA (ΔSUA: 1 versus 0 = decrease versus no change; 2 versus 0 = increase versus no change) with longitudinal annual rate of cognitive change among a large sample of urban adults. Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, 2004-2009 (visit 1) and 2009-2013 (visit 2) were used.

Subclinical carotid atherosclerosis and neurocognitive function in an urban population.

Background And Aims: Examine age, sex, race, and socioeconomic status as modifiers of the association between carotid intimal medial thickness (IMT) and neurocognitive performance in a socioeconomically diverse, biracial, urban, adult population.

Methods: Participants were 1712 community-dwelling adults (45% men, 56% African-American, 38% below poverty threshold, aged 30-64 years) enrolled in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants underwent initial carotid ultrasonography followed by cognitive testing on up to two occasions over 4 years.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

Background: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.