CONTEXT Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an ...interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. OBJECTIVE To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. DATA SOURCES Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. STUDY SELECTION Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, ≥3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. DATA EXTRACTION Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14 250 participants, 1769 were classified as having depression; 12 481 as not having depression. RESULTS In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. CONCLUSION This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.
Little is known about the prevalence and correlates of hoarding behavior in the community. We estimated the prevalence and evaluated correlates of hoarding in 742 participants in the Hopkins ...Epidemiology of Personality Disorder Study. The prevalence of hoarding was nearly 4% (5.3%, weighted) and was greater in older than younger age groups, greater in men than women, and inversely related to household income. Hoarding was associated with alcohol dependence; paranoid, schizotypal, avoidant, and obsessive–compulsive personality disorder traits; insecurity from home break-ins and excessive physical discipline before 16 years of age; and parental psychopathology. These findings suggest that hoarding may be relatively prevalent and that alcohol dependence, personality disorder traits, and specific childhood adversities are associated with hoarding in the community.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Frailty is a well-recognized geriatric syndrome with various definitions and conceptual frameworks. This study aimed to use latent class analysis to discover potential subtypes of pre-frail and frail ...older people. Data from the I-Lan Longitudinal Aging Study (ILAS), a community-based cohort study was used for analysis. Latent class analysis was applied to characterize classes or subgroups with different frailty phenotypes among ILAS participants targeting older adults aged 65 and above, capable of completing a 6-meter walk, without severe major or life threatening diseases, and not institutionalized. Latent class analysis identified three distinct subgroups with different frailty phenotypes: non-mobility-type (weight loss and exhaustion), mobility-type frailty (slowness and weakness), and low physical activity. Comparing these groups with the robust group, people with mobility-type frailty had poorer body composition, worse bone health, poorer cognitive function, lower survival (hazard ratio: 6.82, p = 0.019), and poorer overall health outcomes (hazard ratio: 1.67, p = 0.040). People in the non-mobility-type group had poorer bone health and more metabolic serum abnormalities. In conclusion, mobility-type frailty was a better predictor of adverse outcomes. However, further investigation is needed to evaluate how these phenotypic subgroups may help in predicting prognosis or in developing interventions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The obesity-hypertension link over the life course has not been well characterized, although the prevalence of obesity and hypertension is increasing in the United States.
We studied the association ...of body mass index (BMI) in young adulthood, into middle age, and through late life with risk of developing hypertension in 1132 white men of The Johns Hopkins Precursors Study, a prospective cohort study. Over a median follow-up period of 46 years, 508 men developed hypertension. Obesity (BMI ≥30 kg/m(2)) in young adulthood was strongly associated with incident hypertension (hazard ratio, 4.17; 95% confidence interval, 2.34-7.42). Overweight (BMI 25 to <30 kg/m(2)) also signaled increased risk (hazard ratio, 1.58; 95% confidence interval, 1.28-1.96). Men of normal weight at age 25 years who became overweight or obese at age 45 years were at increased risk compared with men of normal weight at both times (hazard ratio, 1.57; 95% confidence interval, 1.20-2.07), but not men who were overweight or obese at age 25 years who returned to normal weight at age 45 years (hazard ratio, 0.91; 95% confidence interval, 0.43-1.92). After adjustment for time-dependent number of cigarettes smoked, cups of coffee taken, alcohol intake, physical activity, parental premature hypertension, and baseline BMI, the rate of change in BMI over the life course increased the risk of incident hypertension in a dose-response fashion, with the highest risk among men with the greatest increase in BMI (hazard ratio, 2.52; 95% confidence interval, 1.82-3.49).
Our findings underscore the importance of higher weight and weight gain in increasing the risk of hypertension from young adulthood through middle age and into late life.
This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder ...(OCD), to inform TTM classification.
We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders.
TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4).
TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.
•Trichotillomania was classified as an impulse control disorder, is now classified as obsessive-compulsive disorder related•Characterizing the strength of comorbid relations is one of several approaches to classify psychiatric conditions•The current study investigates the strength of relationships between TTM and other DSM-IV Axis I conditions•TTM was most strongly associated with OCD and other conditions previously conceptualized as impulse control disorders•TTM could also classified as a condition involving impaired impulse control/appetitive behavior, or as a grooming disorder
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bipolar, schizophrenia, and schizoaffective disorders are common, highly heritable psychiatric disorders, for which familial coaggregation, as well as epidemiological and genetic evidence, suggests ...overlapping etiologies. No definitive susceptibility genes have yet been identified for any of these disorders. Genetic heterogeneity, combined with phenotypic imprecision and poor marker coverage, has contributed to the difficulty in defining risk variants. We focused on families of Ashkenazi Jewish descent, to reduce genetic heterogeneity, and, as a precursor to genomewide association studies, we undertook a single-nucleotide polymorphism (SNP) genotyping screen of 64 candidate genes (440 SNPs) chosen on the basis of previous linkage or of association and/or biological relevance. We genotyped an average of 6.9 SNPs per gene, with an average density of 1 SNP per 11.9 kb in 323 bipolar I disorder and 274 schizophrenia or schizoaffective Ashkenazi case-parent trios. Using single-SNP and haplotype-based transmission/disequilibrium tests, we ranked genes on the basis of strength of association (
P<.01). Six genes (
DAO, GRM3, GRM4, GRIN2B, IL2RB, and
TUBA8) met this criterion for bipolar I disorder; only
DAO has been previously associated with bipolar disorder. Six genes (
RGS4, SCA1, GRM4, DPYSL2, NOS1, and
GRID1) met this criterion for schizophrenia or schizoaffective disorder; five replicate previous associations, and one,
GRID1, shows a novel association with schizophrenia. In addition, six genes (
DPYSL2, DTNBP1, G30/G72, GRID1, GRM4, and
NOS1) showed overlapping suggestive evidence of association in both disorders. These results may help to prioritize candidate genes for future study from among the many suspected/proposed for schizophrenia and bipolar disorders. They provide further support for shared genetic susceptibility between these two disorders that involve glutamate-signaling pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Often, when a data-generating process is too complex to specify fully, a standard likelihood-based inference is not available. However, a composite likelihood can provide an inference based on a ...partial specification of a data-generating process. Furthermore, its robustness to model specification and computational simplicity makes the composite likelihood method widely applicable. This study conducts a theoretical investigation of the composite likelihood ratio test (CLRT) when the parameters of interest may lie on the boundary of the parameter space. Our main result shows that the limiting distribution of the CLRT is equivalent to that of the likelihood ratio test of a normal mean problem, in which the restricted mean of a multivariate normal distribution is tested based on one observation from a multivariate normal distribution with an inverse Godambe information matrix. Furthermore, we illustrate our general theoretical result by applying it to a variety of examples. Lastly, our simulation results confirm that the limiting distribution of the CLRT performs well in finite samples.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
Composite likelihood has been widely used in applications. The asymptotic distribution of the composite likelihood ratio statistic at the boundary of the parameter space is a complicated mixture of ...weightedχ² distributions. In this paper we propose a conditional test with data-dependent degrees of freedom. We consider a modification of the composite likelihood which satisfies the second-order Bartlett identity. We show that the modified composite likelihood ratio statistic given the number of estimated parameters lying on the boundary converges to a simpleχ² distribution. This conditional testing procedure is validated through simulation studies.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
The case–control study design is one of the main tools for detecting associations between genetic markers and diseases. It is well known that population substructure can lead to spurious association ...between disease status and a genetic marker if the prevalence of disease and the marker allele frequency vary across subpopulations. In this paper, we propose a novel statistical method to estimate the association in case–control studies with unmeasured population substructure. The proposed method takes two steps. First, the information on genomic markers and disease status is used to infer the population substructure; second, the association between the disease and the test marker adjusting for the population substructure is modeled and estimated parametrically through polytomous logistic regression. The performance of the proposed method, relative to the existing methods, on bias, coverage probability and computational time, is assessed through simulations. The method is applied to an end-stage renal disease study in African Americans population.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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