Gene-Environment Interaction Effects on Behavioral Variation and Risk of Complex Disorders: The Example of Alcoholism and Other Psychiatric Disorders

There have been few replicated examples of genotype x environment interaction effects on behavioral variation or risk of psychiatric disorder. We review some of the factors that have made detection of genotype x environment interaction effects difficult, and show how genotype x shared environment interaction (GxSE) effects are commonly confounded with genetic parameters in data from twin pairs reared together. Historic data on twin pairs reared apart can in principle be used to estimate such GxSE effects, but have rarely been used for this purpose. We illustrate this using previously published data from the Swedish Adoption Twin Study of Aging (SATSA), which suggest that GxSE effects could account for as much as 25% of the total variance in risk of becoming a regular smoker. Since few separated twin pairs will be available for study in the future, we also consider methods for modifying variance components linkage analysis to allow for environmental interactions with linked loci.

Personality and the genetic risk for alcohol dependence

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest. whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol. account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women.

Sun exposure and interaction with family history in risk of melanoma, Queensland, Australia

Sun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age-specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population-based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first-degree relatives without melanoma as controls. Data an lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important. (C) 2002 Wiley-Liss, Inc.

Melanoma in adolescents: A case-control study of risk factors in Queensland, Australia

The incidence of melanoma increases markedly in the second decade of life but almost nothing is known of the causes of melanoma in this age group. We report on the first population-based case-control study of risk factors for melanoma in adolescents (15-19 years). Data were collected through personal interviews with cases, controls and parents. A single examiner conducted full-body nevus counts and blood samples were collected from cases for analysis of the CDKN2A melanoma predisposition gene. A total of 201 (80%) of the 250 adolescents with melanoma diagnosed between 1987 and 1994 and registered with the Queensland Cancer Registry and 205 (79%) of 258 age-, gender- and location-matched controls who were contacted agreed to participate. The strongest risk factor associated with melanoma in adolescents in a multivariate model was the presence of more than 100 nevi 2 mm or more in diameter (odds ratio [OR] = 46.5, 95% confidence interval [Cl] = 11.4-190.8). Other risk factors were red hair (OR = 5.4, 95%Cl = 1.0-28.4); blue eyes (OR = 4.5, 95%Cl = 1.5- 13.6); inability to tan after prolonged sun exposure (OR = 4.7, 95%Cl = 0.9-24.6); heavy facial freckling (OR = 3.2, 95% Cl = 0.9-12.3); and family history of melanoma (OR = 4.0, 95%Cl = 0.8-18.9). Only 2 of 147 cases tested had germline variants or mutations in CDKN2A. There was no association with sunscreen use overall, however, never/rare use of sunscreen at home under the age of 5 years was associated with increased risk (OR = 2.2, 95%Cl = 0.7-7.1). There was no difference between cases and controls in cumulative sun exposure in this high-exposure environment. Factors indicating genetic susceptibility to melanoma, in particular, the propensity to develop nevi and freckles, red hair, blue eyes, inability to tan and a family history of the disease are the primary determinants of melanoma among adolescents in this high solar radiation environment. Lack of association with reported sun exposure is consistent with the high genetic susceptibility in this group. (C) 2002 Wiley-Liss, Inc.

Short communication: Extended shifts in ambulance work: influences on health

Shiftwork is a major source of stress for many worker's. This study highlights the role that organizational and psychosocial variables play in alleviating the negative health effects of 10 and 14-h shifts. It examines the direct and mediated effects of coping strategies, social support and control of shifts on work/non-work conflict and subjective health. Participants are 60 ambulance workers, aged 22 to SS years. A structural equation model with good fit demonstrates complex effects of social support from various sources (supervisors, co-workers and family), coping and control on work/non-work conflict and subjective health., Conceptually, the research contributes to the development of a theoretical framework that can assist in explaining how key psychosocial and organizational variables influence the psychological and physical symptoms experienced by shiftworkers. Copyright (C) 2002 John Wiley Sons, Ltd.

Air target detection via bistatic radar based on LEOS communication signals

The paper discusses the bistatic radar parameters for the case when the transmitter is a satellite emitting communication signals. The model utilises signals from an Iridium-like low earth orbiting satellite system. The maximum detection range, when thermal noise-limited, is discussed at the theoretical level and these results are compared with experimentation. Satellite-radar signal levels and the power of ground reflections are evaluated.

Usefulness of clinical risk markers and ischemic threshold to stratify risk in patients undergoing major noncardiac surgery

The risk of cardiac events in patients undergoing major noncardiac surgery is dependent on their clinical characteristics and the results of stress testing. The purpose of this study was to develop a composite approach to defining levels of risk and to examine whether different approaches to prophylaxis influenced this prediction of outcome. One hundred forty-five consecutive patients (aged 68 +/- 9 years, 79 men) with >1 clinical risk variable were studied with standard dobutamine-atropine stress echo before major noncardiac surgery. Risk levels were stratified according to the presence of ischemia (new or worsening wall motion abnormality), ischemic threshold (heart rate at development of ischemia), and number of clinical risk variables. Patients were followed for perioperative events (during hospital admission) and death or infarction over the subsequent 16 10 months. Ten perioperative events occurred in 105 patients who proceeded to surgery (10%, 95% confidence interval [CI] 5% to 17%), 40 being cancelled because of cardiac or other risk. No ischemia was identified in 56 patients, 1 of whom (1.8%) had a perioperative infarction. Of the 49 patients with ischemia, 22 (45%) had 1 or 2 clinical risk factors; 2 (9%, 95% CI 1% to 29%) had events. Another 15 patients had a high ischemic threshold and 3 or 4 risk factors; 3 (20%, 95% Cl 4% to 48%) had events. Twelve patients had a low ischemic threshold and 3 or 4 risk factors; 4 (33%, 95% CI 10% to 65%) had events. Preoperative myocardial revascularization was performed in only 3 patients, none of whom had events. Perioperative and long-term events occurred despite the use of beta blockers; 7 of 41 eta blocker-treated patients had a perioperative event (17%, 95% CI 7% to 32%); these treated patients were at higher anticipated risk than untreated patients (20 +/- 24% vs 10 +/- 19%, p = 0.02). The total event rate over late follow-up was 13%, and was predicted by dobutamine-atropine stress echo results and heart rate response. (C) 2002 by Excerpta Medica, Inc.

Myocardial infarction and type II diabetes - preferential treatment for high risk patients?

Objectives: To compare variability of blood glucose concentration in patients with type II diabetes with (cases) and without (controls) myocardial infarction. A secondary objective was identification of predictive factors for higher blood glucose on discharge from hospital. Design: A retrospective matched case-control study. Participants: Medical notes of 101 type II diabetic patients admitted with a myocardial infarction (MI) and 101 type II diabetic patients (controls) matched on gender and age with no MI were reviewed. Blood glucose concentrations over two consecutive 48-h periods were collected. Demographic data and therapy on admission/discharge were also collected. Results: Patient characteristics were comparable on recruitment excluding family history of cardiovascular disease (P =0.003), dyslipidaemia (P =0.004) and previous history of MI (P =0.007). Variability of blood glucose in cases was greater over the first 48 h compared with the second 48 h (P =0.03), and greater when compared with controls over the first 48 h (P =0.01). Cases with blood glucose on discharge >8.2 mmol / L (n =45) were less likely to have a history of previous MI (P =0.04), ischaemic heart disease (P =0.03) or hypertension (P =0.02). Conclusions: Type II diabetics with an MI have higher and more variable blood glucose concentrations during the first 48 h of admission. Only cardiovascular 'high risk' patients had target blood glucose set on discharge. The desirability of all MI patients with diabetes, having standardized-glucose infusions to reduce variability of blood glucose, should be evaluated in a randomized controlled trial.