Robust and Powerful Affected Sibpair Test for Rare Variant Association.

Advances in DNA sequencing technology facilitate investigating the impact of rare variants on complex diseases. However, using a conventional case-control design, large samples are needed to capture enough rare variants to achieve sufficient power for testing the association between suspected loci and complex diseases. In such large samples, population stratification may easily cause spurious signals. One approach to overcome stratification is to use a family-based design. For rare variants, this strategy is especially appropriate, as power can be increased considerably by analyzing cases with affected relatives. We propose a novel framework for association testing in affected sibpairs by comparing the allele count of rare variants on chromosome regions shared identical by descent to the allele count of rare variants on nonshared chromosome regions, referred to as test for rare variant association with family-based internal control (TRAFIC). This design is generally robust to population stratification as cases and controls are matched within each sibpair. We evaluate the power analytically using general model for effect size of rare variants. For the same number of genotyped people, TRAFIC shows superior power over the conventional case-control study for variants with summed risk allele frequency f < 0.05; this power advantage is even more substantial when considering allelic heterogeneity. For complex models of gene-gene interaction, this power advantage depends on the direction of interaction and overall heritability. In sum, we introduce a new method for analyzing rare variants in affected sibpairs that is robust to population stratification, and provide freely available software.

The genetic architecture of dog ownership: large-scale genome-wide association study in 97,552 European-ancestry individuals.

Dog ownership has been associated with several complex traits and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through meta-analysis of 31,566 Swedish twins in five discovery cohorts and additional 65,986 European-ancestry individuals in three replication cohorts from Sweden, Norway, and the UK. Association test with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified two suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphisms-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002, 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence the dog ownership among European-ancestry individuals.

Gender differences in lifetime alcohol dependence: results from the national epidemiologic survey on alcohol and related conditions.

BACKGROUND: An extensive clinical literature has noted gender differences in the etiology and clinical characteristics of individuals with alcohol dependence (AD). Despite this knowledge, many important questions remain. METHODS: Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093), we examined differences in sociodemographic characteristics, psychiatric and medical comorbidities, clinical correlates, risk factors, and treatment-utilization patterns of men (N = 2,974) and women (N = 1,807) with lifetime AD. RESULTS: Men with lifetime AD were more likely than women to be diagnosed with any substance use disorder and antisocial personality disorder, whereas women were more likely to have mood and anxiety disorders. After adjusting for sociodemographic characteristics and gender differences in psychiatric comorbidity in the general population, AD was associated with externalizing disorders and any mood disorder among women only. Men with AD met more criteria, had longer episodes, and were younger at the age of first drink. There were no gender differences in remission rates. Women with AD were more likely to have a family and a spouse with history of alcohol use disorders. Treatment rates were low for both genders, and women were more likely to report social stigmatization as a treatment barrier. CONCLUSIONS: There are important gender differences in the psychiatric comorbidities, risk factors, clinical characteristics, and treatment-utilization patterns among individuals with lifetime AD.

Child physical abuse and adult mental health: a national study.

This study characterizes adults who report being physically abused during childhood, and examines associations of reported type and frequency of abuse with adult mental health. Data were derived from the 2000-2001 and 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the U.S. population. Weighted means, frequencies, and odds ratios of sociodemographic correlates and prevalence of psychiatric disorders were computed. Logistic regression models were used to examine the strength of associations between child physical abuse and adult psychiatric disorders adjusted for sociodemographic characteristics, other childhood adversities, and comorbid psychiatric disorders. Child physical abuse was reported by 8% of the sample and was frequently accompanied by other childhood adversities. Child physical abuse was associated with significantly increased adjusted odds ratios (AORs) of a broad range of DSM-IV psychiatric disorders (AOR = 1.16-2.28), especially attention-deficit hyperactivity disorder, posttraumatic stress disorder, and bipolar disorder. A dose-response relationship was observed between frequency of abuse and several adult psychiatric disorder groups; higher frequencies of assault were significantly associated with increasing adjusted odds. The long-lasting deleterious effects of child physical abuse underscore the urgency of developing public health policies aimed at early recognition and prevention.

Epidemiology of chronic and nonchronic major depressive disorder: results from the national epidemiologic survey on alcohol and related conditions.

BACKGROUND: Burden related to major depressive disorder (MDD) derives mostly from long-term occurrence of symptoms. This study aims to examine the prevalence, sociodemographic correlates, patterns of 12-month and lifetime psychiatric comorbidity, lifetime risk factors, psychosocial functioning, and mental health service utilization of chronic major depressive disorder (CMDD) compared to nonchronic major depressive disorder. METHODS: Face-to-face interviews were conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093). RESULTS: The 12-month and lifetime prevalence of CMDD within the population meeting criteria for MDD was 26.5% and 24.0%, respectively. Individuals reporting a chronic course of MDD were socioeconomically and educationally disadvantaged, tended to be older, report loss of spouse or history of divorce, live in rural areas, have public assistance, low self-esteem, worse overall health and more likely to report comorbidities, most importantly dysthymia, generalized anxiety disorder, avoidant, and dependant personality disorder. Individuals with chronic MDD were more likely to report familial but not childhood onset risk factors for MDD. Those suffering CMDD were more likely to seek and receive mental health care than other forms of MDD, even though it took longer to start treatment. CONCLUSION: Chronic course of MDD is related to still worse socioeconomic conditions, educational achievement, more comorbidities, and family risk factors, although other courses of MDD carried greater risk of unmet treatment.

Subtypes of disordered gamblers: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

AIMS: To derive empirical subtypes of problem gamblers based on etiological and clinical characteristics described in the Pathways Model, using data from a nationally representative survey of US adults. DESIGN & MEASUREMENT: Data were collected from structured diagnostic face-to-face interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV version IV (AUDADIS-IV). SETTING: The study utilized data from US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). PARTICIPANTS: All disordered gambling participants (n = 581) from a nationally representative cross-sectional sample of civilian non-institutionalized adults aged 18 years or older. FINDINGS: Latent class analyses indicated that the best-fitting model was a three-class solution. Those in the largest class (class 1: 50.76%, n = 295) reported the lowest overall levels of psychopathology including gambling problem severity and mood disorders. In contrast, respondents in class 2 (20.06%, n = 117) had a high probability of endorsing past-year substance use disorders, moderate probabilities of having parents with alcohol/drug problems and of having a personality disorder, and the highest probability for past-year mood disorders. Respondents in class 3 (29.18%, n = 169) had the highest probabilities of personality and prior-to-past year mood disorders, substance use disorders, separation/divorce, drinking-related physical fights and parents with alcohol/drug problems and/or a history of antisocial personality disorder (ASPD). CONCLUSIONS: Three subtypes of disordered gamblers can be identified, roughly corresponding to the subtypes of the Pathways Model, ranging from a subgroup with low levels of gambling severity and psychopathology to one with high levels of gambling problem severity and comorbid psychiatric disorders.

Gender, HIV status, and psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: More than 30 years after the onset of the human immunodeficiency virus (HIV) epidemic, there is no information on the prevalence of psychiatric disorders among HIV-positive individuals in the general population. We sought to compare the prevalence of 12-month psychiatric disorders among HIV-positive and HIV-negative adults stratified by sex and to examine the differential increase in risk of a psychiatric disorder as a function of the interaction of sex and HIV status. METHOD: Face-to-face interviews were conducted between 2004 and 2005 with participants in the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2, a large nationally representative sample of US adults (34,653). The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. RESULTS: When compared with their HIV-negative same-sex counterparts, HIV-positive men were more likely to have any mood disorder (odds ratio [OR] = 6.10; 95% confidence interval [CI], 2.99-12.44), major depressive disorder/dysthymia (OR = 3.77; 95% CI, 1.16-12.27), any anxiety disorder (OR = 4.02; 95% CI, 2.12-7.64), and any personality disorder (OR = 2.50; 95% CI, 1.34-4.67). In relation to their same-sex HIV-negative counterparts, the effect of HIV status on the odds of any mood disorder (OR = 7.17; 95% CI, 2.52-20.41), any anxiety disorder (OR = 3.45; 95% CI, 1.27-9.38), and any personality disorder (OR = 2.66; 95% CI, 1.16-6.10) was significantly greater for men than women. CONCLUSIONS: HIV status was significantly more strongly associated with psychiatric disorders in men than in women. HIV-positive men had a higher prevalence than HIV-negative men of most psychiatric disorders. By contrast, HIV-positive women were not significantly more likely than HIV-negative women to have psychiatric disorders.

Exercise and mental illness: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

BACKGROUND: Regular exercise is thought to be associated with low rates of mental illness, but this association has been inadequately studied. The purpose of this study was to test the hypotheses that the recommended amount of self-reported vigorous exercise would be cross-sectionally associated with reduced prevalence and incidence of various DSM-IV psychiatric disorders, as well as increased rates of remission. METHOD: Data were collected from 2001 to 2005 as part of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a 2-wave face-to-face survey conducted by the National Institute on Alcohol Abuse and Alcoholism. For this study, the sample consisted of 23,505 nondisabled adults aged between 18 and 65 years. RESULTS: Individuals who engaged in vigorous exercise at Wave 2 were significantly more likely than were nonexercisers to be diagnosed with a current psychiatric disorder (adjusted odds ratio [AOR] = 1.22, 95% CI, 1.12-1.34 for the nationally recommended amount vs no exercise), significantly less likely to attain remission from a psychiatric disorder between waves (AOR = 0.77, 95% CI, 0.65-0.91), and significantly more likely to relapse or be newly diagnosed with a psychiatric disorder between waves (AOR = 1.15, 95% CI, 1.02-1.30). Alcohol dependence and bipolar II disorder were the disorders most strongly associated with exercise. CONCLUSIONS: This investigation suggests that the pursuit of vigorous exercise is associated with a vulnerability to mental illness. This surprising finding may be due to reward-related factors that influence both exercise engagement and the expression of certain psychiatric disorders. Prospective trials will be helpful in further clarifying the associations between exercise and mental illness, as the relationships between the 2 are more complex than previously believed.

Racial and ethnic differences in diabetes mellitus among people with and without psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: This study examined racial/ethnic differences in the prevalence of diabetes mellitus in a nationally representative sample of adults with and without common psychiatric disorders. METHOD: Data were drawn from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (N=34,653). Logistic regression models adjusting for sociodemographic variables and diabetes risk factors were used to examine racial/ethnic differences in 12-month prevalence rates of diabetes by psychiatric status. RESULTS: Among people without psychiatric disorders, African Americans, Hispanics and American Indians/Alaska Natives, but not Asians/Pacific Islanders, had significantly higher rates of diabetes than non-Hispanic whites even after adjusting for sociodemographic variables and diabetes risk factors. In the presence of psychiatric disorders, these health disparities persisted for African Americans and Hispanics, but not for American Indians/Alaska Natives. No significant interactions between race/ethnicity and psychiatric disorders in the odds of diabetes were found across any group. CONCLUSION: Policies and services that support culturally appropriate prevention and treatment strategies are needed to reduce racial/ethnic disparities in diabetes among people with and without psychiatric disabilities.

Mental health of victims of intimate partner violence: results from a national epidemiologic survey.

OBJECTIVE: This study assessed the national incidence and mental health correlates of recent intimate partner violence among adults interviewed by the wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. METHODS: Data were collected about minor and severe forms of intimate partner violence among adults who reported being married, recently married, or in a romantic relationship in the past 12 months (N=25,626). RESULTS: A total of 1,608 individuals reported being victims of intimate partner violence, including 5.8% of men and 5.6% of women. New onset of axis I disorders was significantly more common among victims of intimate partner violence than among nonvictims (22.5% and 9.7%, respectively; OR=2.6) and was related to frequency of violent acts. CONCLUSIONS: Intimate partner violence is common, and victimization, especially if recurrent, markedly increases the risk for developing several psychiatric disorders.