Search

PurposeSymptoms of urinary irritation, urgency, frequency and obstruction, known as lower urinary tract symptoms, are common in urological practice. However, little is known about the etiology or pathogenesis of lower urinary tract symptoms, especially the relative contributions of genetic and environmental factors to the development of these symptoms. We used a classic twin study design to examine the relative contributions of genetic and environmental factors to the occurrence of lower urinary tract symptoms in middle-aged men.Materials and methodsTwins were members of the Vietnam Era Twin Registry. We used a mail survey to collect data on lower urinary tract symptoms using the I-PSS (International Prostate Symptom Score) instrument. Twin correlations and biometric modeling were used to determine the relative genetic and environmental contributions to variance in I-PSS total score and individual items.ResultsParticipants were 1,002 monozygotic and 580 dizygotic middle-aged male twin pairs (mean age 50.2 years, SD 3.0). Nearly 25% of the sample had an I-PSS greater than 8, indicating at least moderate lower urinary tract symptoms. The heritability of the total I-PSS was 37% (95% CI 32-42). Heritability estimates ranged from 21% for nocturia to 40% for straining, with moderate heritability (34% to 36%) for urinary frequency and urgency.ConclusionsGenetic factors provide a moderate contribution (20% to 40%) to lower urinary tract symptoms in middle-aged men, suggesting that environmental factors may also contribute substantially to lower urinary tract symptoms. Future research is needed to define specific genetic and environmental mechanisms that underlie the development of these symptoms and conditions associated with lower urinary tract symptoms.

Objectives. We examined the association between race and hepatitis C virus (HCV) evaluation and treatment of veterans in the Northwest Network of the Department of Veterans Affairs (VA). Methods. In our retrospective cohort study, we used medical records to determine antiviral treatment of 4263 HCV-infected patients from 8 VA medical centers. Secondary outcomes included specialty referrals, laboratory evaluation, viral genotype testing, and liver biopsy. Multiple logistic regression was used to adjust for clinical (measured through laboratory results and International Classification of Diseases, Ninth Revision, codes) and sociodemographic factors. Results. Blacks were less than half as likely as Whites to receive antiviral treatment (odds ratio [OR] = 0.38; 95% confidence interval [CI] = 0.23, 0.63). Both had similar odds of referral and liver biopsy. However, Blacks were significantly less likely to have complete laboratory evaluation (OR = 0.67; 95% CI = 0.52, 0.88) and viral genotype testing (OR = 0.68; 95% CI = 0.51, 0.90). Conclusions. Race is associated with receipt of medical care for various medical conditions. Further investigation is warranted to help understand whether patient preference or provider bias may explain why HCV-infected Blacks were less likely to receive medical care than Whites. (doi: 10.2105/AJ PH.2007.113225)

Major Depressive Disorder (MDD) is a complex neuropsychiatric disease with known genetic associations, but without known links to rare variation in the human genome. Here we aim to identify rare genetic variants associated with MDD using deep whole-genome sequencing data in an independent population. We report the sequencing of 1,688 whole genomes in a large sample of male-male Veteran twins. Depression status was classified based on a structured diagnostic interview according to DSM-III-R diagnostic criteria. Searching only rare variants in genomic regions from recent GWAS on MDD, we used the optimised sequence kernel association test and Fisher's Exact test to fine map loci associated with severe depression. Our analysis identified one gene associated with severe depression, basic helix loop helix e22 (PAdjusted = 0.03) via SKAT-O test between unrelated severely depressed cases compared to unrelated non-depressed controls. The same gene BHLHE22 had a non-silent variant rs13279074 (PAdjusted = 0.032) based on a single variant Fisher's Exact test between unrelated severely depressed cases compared to unrelated non-depressed controls. The gene BHLHE22 shows compelling genetic evidence of directly impacting the severe depression phenotype. Together these results advance understanding of the genetic contribution to major depressive disorder in a new cohort and link a rare variant to severe forms of the disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. Methods We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. Results When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. Conclusions The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease.

Background: Military veterans provide a large and diverse population to examine the extent to which compulsory physical activity (PA) in early adulthood is associated with PA later in life. Methods: We assessed self-reported and objectively measured PA and sedentary time in the 900 veterans and 2036 nonveterans with valid data from the 2003-2006 National Health and Nutrition Examination Surveys. Analyses were adjusted for the complex survey design and age, race/ethnicity, education, marital status, and poverty. Results: Based on self-report, the proportion of veterans and nonveterans meeting PA Guidelines did not differ significantly (51.1% vs. 43.9%, P = .26). However, a greater proportion of veterans reported regular vigorous leisure-time activity (30.4% vs. 19.6%, P = .04) and muscle-strengthening activities (24.4 vs. 16.7, P = .051). Based on objective PA monitoring, activity levels between veterans and nonveterans also did not differ significantly, although mean counts and minutes per day were numerically greater in nonveterans. By self-report (P = .02) and PA monitors (P = .065), estimated sedentary time was greater in veterans than in demographically similar nonveterans. Conclusions: Veterans were no more likely than nonveterans to meet PA Guidelines, but may have been more likely to perform vigorous activities and conversely, to spend more time in sedentary activities. [ABSTRACT FROM AUTHOR]

Little is known about the population genetics of water balance. A recent meta-genome-wide association study on plasma sodium concentration identified novel loci of high biological plausibility, yet heritability of the phenotype has never been convincingly shown in European ancestry. The present study linked the Vietnam Era Twin Registry with the Department of Veterans Affairs VistA patient care clinical database. Participants (n = 2,370, 59.6% monozygotic twins and 40.4% dizygotic twins) had a median of seven (interquartile range: 3-14) plasma sodium determinations between October 1999 and March 2017. Heritability of the mean plasma sodium concentration among all twins was 0.41 (95% confidence interval: 0.35-0.46) and 0.49 (95% confidence interval: 0.43-0.54) after exclusion of 514 twins with only a single plasma sodium determination. Heritability among Caucasian (n = 1,958) and African-American (n = 268) twins was 0.41 (95% confidence interval: 0.34-0.47) and 0.36 (95% confidence interval: 0.17-0.52), respectively. Exclusion of data from twins who had been prescribed medications known to impact systemic water balance had no effect. The ability of the present study to newly detect substantial heritability across multiple racial groups was potentially a function of the cohort size and relatedness, exclusion of sodium determinations confounded by elevated plasma glucose and/or reduced glomerular filtration rate, transformation of plasma sodium for the independent osmotic effect of plasma glucose, and use of multiple laboratory determinations per individual over a period of years. Individual-level plasma sodium concentration exhibited longitudinal stability (i.e., individuality); the degree to which individual-level means differed from the population mean was substantial, irrespective of the number of determinations. In aggregate, these data establish the heritability of plasma sodium concentration in European ancestry and corroborate its individuality. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. Methods: We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. Results: When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. Conclusions: The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease. [ABSTRACT FROM AUTHOR]

Background: The media has devoted significant attention to anecdotes of individuals who post messages on Facebook prior to suicide. However, it is unclear to what extent social media is perceived as a source of help or how it compares to other sources of potential support for mental health problems.Objective: This study aimed to evaluate the degree to which military veterans with depression use social media for help-seeking in comparison to other more traditional sources of help.Methods: Cross-sectional self-report survey of 270 adult military veterans with probable major depression. Help-seeking intentions were measured with a modified General Help-Seeking Questionnaire. Facebook users and nonusers were compared via t tests, Chi-square, and mixed effects regression models. Associations between types of help-seeking were examined using mixed effects models.Results: The majority of participants were users of social media, primarily Facebook (n=162). Mean overall help-seeking intentions were similar between Facebook users and nonusers, even after adjustment for potential confounders. Facebook users were very unlikely to turn to Facebook as a venue for support when experiencing either emotional problems or suicidal thoughts. Compared to help-seeking intentions for Facebook, help-seeking intentions for formal (eg, psychologists), informal (eg, friends), or phone helpline sources of support were significantly higher. Results did not substantially change when examining users of other social media, women, or younger adults.Conclusions: In its current form, the social media platform Facebook is not seen as a venue to seek help for emotional problems or suicidality among veterans with major depression in the United States. [ABSTRACT FROM AUTHOR]