American Journal of Epidemiology - current issueTable of contents Subscriptions Editorial Board Cover Towards Reducing Disparities in Disparities ResearchRowland Hogue, C. J.
Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data SetsPereira, T. V., Patsopoulos, N. A., Salanti, G., Ioannidis, J. P. A.
Genetic effects for common variants affecting complex disease risk are subtle. Single genome-wide association (GWA) studies are typically underpowered to detect these effects, and combination of several GWA data sets is needed to enhance discovery. The authors investigated the properties of the discovery process in simulated cumulative meta-analyses of GWA study-derived signals allowing for potential genetic model misspecification and between-study heterogeneity. Variants with null effects on average (but also between-data set heterogeneity) could yield false-positive associations with seemingly homogeneous effects. Random effects had higher than appropriate false-positive rates when there were few data sets. The log-additive model had the lowest false-positive rate. Under heterogeneity, random-effects meta-analyses of 2–10 data sets averaging 1,000 cases/1,000 controls each did not increase power, or the meta-analysis was even less powerful than a single study (power desert). Upward bias in effect estimates and underestimation of between-study heterogeneity were common. Fixed-effects calculations avoided power deserts and maximized discovery of association signals at the expense of much higher false-positive rates. Therefore, random- and fixed-effects models are preferable for different purposes (fixed effects for initial screenings, random effects for generalizability applications). These results may have broader implications for the design and interpretation of large-scale multiteam collaborative studies discovering common gene variants.
Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC ReviewTaioli, E., Garza, M. A., Ahn, Y. O., Bishop, D. T., Bost, J., Budai, B., Chen, K., Gemignani, F., Keku, T., Lima, C. S. P., Le Marchand, L., Matsuo, K., Moreno, V., Plaschke, J., Pufulete, M., Thomas, S. B., Toffoli, G., Wolf, C. R., Moore, C. G., Little, J.
Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.
Genetic Variations in Xenobiotic Metabolic Pathway Genes, Personal Hair Dye Use, and Risk of Non-Hodgkin LymphomaZhang, Y., Hughes, K. J., Zahm, S. H., Zhang, Y., Holford, T. R., Dai, L., Bai, Y., Han, X., Qin, Q., Lan, Q., Rothman, N., Zhu, Y., Leaderer, B., Zheng, T.
From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T>A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A>G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies.
Body Size, Recreational Physical Activity, and B-Cell Non-Hodgkin Lymphoma Risk Among Women in the California Teachers StudyLu, Y., Prescott, J., Sullivan-Halley, J., Henderson, K. D., Ma, H., Chang, E. T., Clarke, C. A., Horn-Ross, P. L., Ursin, G., Bernstein, L.
Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.
Epidemiologic Reviews - current issueThe Burden of Mental DisordersEaton, W. W., Martins, S. S., Nestadt, G., Bienvenu, O. J., Clarke, D., Alexandre, P.
In the last decade, there has been an increase in interest in the burden of chronic and disabling health conditions that are not necessarily fatal, such as the mental disorders. This review systematically summarizes data on the burden associated with 11 major mental disorders of adults. The measures of burden include estimates of prevalence, mortality associated with the disorders, disabilities and impairments related to the disorders, and costs. This review expands the range of mental disorders considered in a report on the global burden of disease, updates the literature, presents information on the range and depth of sources of information on burden, and adds estimates of costs. The purpose is to provide an accessible guide to the burden of mental disorders, especially for researchers and policy makers who may not be familiar with this subfield of epidemiology.
Dementia of the Alzheimer TypeJalbert, J. J., Daiello, L. A., Lapane, K. L.
Dementia of the Alzheimer type is a progressive, fatal neurodegenerative condition characterized by deterioration in cognition and memory, progressive impairment in the ability to carry out activities of daily living, and a number of neuropsychiatric symptoms. This narrative review summarizes the literature regarding descriptive epidemiology, clinical course, and characteristic neuropathological changes of dementia of the Alzheimer type. Although there are no definitive imaging or laboratory tests, except for brain biopsy, for diagnosis, brief screening instruments and neuropsychiatric test batteries used to assess the disease are discussed. Insufficient evidence exists for the use of biomarkers in clinical practice for diagnosis or disease management, but promising discoveries are summarized. Optimal treatment requires both nonpharmacological and pharmacological interventions, yet none have been shown to modify the disease's clinical course. This review describes the current available options and summarizes promising new avenues for treatment. Issues related to the care of persons with dementia of the Alzheimer type, including caregiver burden, long-term care, and the proliferation of dementia special care units, are discussed. Although advances have been made, more research is needed to address the gaps in our understanding of the disease.
Dementia Prevention: Methodological Explanations for Inconsistent ResultsColey, N., Andrieu, S., Gardette, V., Gillette-Guyonnet, S., Sanz, C., Vellas, B., Grand, A.
The prevention of neurodegenerative dementias, such as Alzheimer disease, is a growing public health concern, because of a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiologic research, including modifiable lifestyle factors, such as social contacts, leisure activities, physical exercise, and diet, as well as some preventive pharmacologic strategies, such as hormone replacement therapy, nonsteroidal antiinflammatory drugs, and Ginkgo biloba. Some factors have been targeted by interventions tested in randomized controlled trials, but many of the results are in conflict with observational evidence. The aim of this paper is to review the epidemiologic data linking potential protective factors to dementia or cognitive decline and to discuss the methodological limitations that could explain conflicting results. A thorough review of the literature suggests that, even if there are consistent findings from large observational studies regarding preventive or risk factors for dementia, few randomized controlled trials have been designed specifically to prove the protective effects of interventions based on such factors on dementia incidence. Because of the multifactorial origin of dementia, it appears that multidomain interventions could be a suitable candidate for preventive interventions, but designing such trials remains very challenging for researchers.
Schizophrenia: A Concise Overview of Incidence, Prevalence, and MortalityMcGrath, J., Saha, S., Chant, D., Welham, J.
Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7–43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.
Population-based Cohort Studies on Premorbid Cognitive Function in SchizophreniaMacCabe, J. H.
Many previous studies have found associations between poor cognitive function and schizophrenia. However, the majority of these studies used retrospective data, leading to the possibility of selection and recall biases. Retrospective studies are also unable to distinguish whether cognitive deficits exist prior to the onset of schizophrenia, suggesting that they are important in etiology, or following onset, suggesting that they are secondary to the disorder or its treatment. The current review used a systematic search strategy to identify and summarize the results of all studies that have used population-based cohorts to examine associations between prospectively collected data on premorbid cognitive functioning in childhood or adolescence and subsequent risk for schizophrenia. Three broad categories of study have addressed these questions: birth cohort designs with cognitive testing during childhood, army conscript designs with cognitive performance measured at conscription, and studies using school grades. Birth cohort and conscript studies are consistent in reporting strong associations between poor performance on cognitive batteries and increased risk of schizophrenia. Studies on school performance have been less consistent, although the largest such study showed strong associations across all school subjects. In conclusion, children and adolescents with poor cognitive abilities in childhood are at increased risk of schizophrenia. This suggests that poor cognitive function is either directly causal or associated with causal factors that are involved in etiology.
Psychosis and PlaceMarch, D., Hatch, S. L., Morgan, C., Kirkbride, J. B., Bresnahan, M., Fearon, P., Susser, E.
One important line of epidemiologic inquiry implicating social context in the etiology of psychosis is the examination of spatial variation in the distribution of psychotic illness. The authors conducted a systematic review of evidence from urbanicity and neighborhood studies regarding spatial variation in the incidence of psychosis in developed countries since 1950. A total of 44 studies (20 of urbanicity and 24 of neighborhood) were culled from three databases with similar time frames: Medline (1950–2007), PsychInfo (1950–2007), and Sociological Abstracts (1952–2007). With a special emphasis on social factors potentially relevant to etiology, the authors elucidated contributions, limitations, and issues related to study design, measurement, and theory. Evidence from both arenas supports a possible etiologic role for social context. Studies of urbanicity indicate that early-life exposure may be important; dose-response relations, spatial patterning of schizophrenia, and interactions with other factors may exist. Neighborhood studies indicate heterogeneity in rates, hint at spatial patterning of schizophrenia, and offer intriguing evidence implying more proximal social (as opposed to physical) exposures. The authors encourage the exploration of social pathways engaging theory, methodological advances, and the life-course perspective. They also propose a conceptual shift from studies of spatial variation in outcomes to research addressing the etiologic effect of exposures shaped by place as a reservoir of risk or resilience.
Epidemiology and Infection - Current IssueVolume 137 Issue 12 Tue, 01 Dec 2009 00:00:00 -0000
Epidemiology and Infection, Volume 137 Issue 12 Increased frequency in 2007 - now 8 issues per year!
Epidemiology and Infection publishes original reports and reviews on all aspects of infection in humans and animals. Particular emphasis is given to the epidemiology, prevention and control of infectious diseases. The field covered is broad and includes the zoonoses, tropical infections, food hygiene, vaccine studies, statistics and the clinical, social and public-health aspects of infectious disease. Papers covering microbiology and immunology which have an epidemiological relevance are part of this broad field. Papers come from medical and veterinary scientists worldwide. It has become the key periodical in which to find the latest reports on recently discovered infections and new technology. For those concerned with policy and planning for the control of infections, the papers on mathematical modelling of epidemics caused by historical, current and emergent infections, will be of particular value. To celebrate 100 years of the journal, a series of important papers has been selected and each, together with a modern commentary on the paper by an expert, will be published on-line. This journal has now moved over to electronic submission, using the Scholar One system. Click here to go to the submission website. Guidance on how to upload your manuscript is available on the site by clicking "User Tutorials".
Online manuscript submission (now) available, please go to http://mc.manuscriptcentral.com/cup/hyg
HYG volume 137 issue 12 Cover and Front matterMiscellaneous Epidemiology and Infection, Volume 137 Issue 12 , pp f1-f2Abstract
HYG volume 137 issue 12 Cover and Back matterMiscellaneous Epidemiology and Infection, Volume 137 Issue 12 , pp b1-b2Abstract
Surveillance for antimicrobial resistant organisms: potential sources and magnitude of biasReview ArticlesO. R. REMPEL, K. B. LAUPLAND, Epidemiology and Infection, Volume 137 Issue 12 , pp 1665-1673Abstract
Surveillance for severe community-associated methicillin-resistant Staphylococcus aureus infectionResearch ArticlesP. WIERSMA, M. TOBIN D'ANGELO, W. R. DALEY, J. TUTTLE, K. E. ARNOLD, S. M. RAY, J. L. LADSON, S. N. BULENS, C. L. DRENZEK, Epidemiology and Infection, Volume 137 Issue 12 , pp 1674-1678Abstract
Rates of Stenotrophomonas maltophilia colonization and infection in relation to antibiotic cycling protocolsBrief ReportA. L. PAKYZ, B. M. FARR, Epidemiology and Infection, Volume 137 Issue 12 , pp 1679-1683Abstract
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