Gamma-heavy chain disease associated with MALT lymphoma of the duodenum

BACKGROUND: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. METHODS: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). CONCLUSIONS: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.     

Genetic and environmental influences on antisocial behavior: A meta-analysis of twin and adoption studies.

A meta-analysis of 51 twin and adoption studies was conducted to estimate the magnitude of genetic and environmental influences on antisocial behavior. The best fitting model included moderate proportions of variance due to additive genetic influences (.32), nonadditive genetic influences (.09), shared environmental influences (.16), and nonshared environmental influences (.43). The magnitude of familial influences (i.e., both genetic and shared environmental influences) was lower in parent-offspring adoption studies than in both twin studies and sibling adoption studies. Operationalization, assessment method, zygosity determination method, and age were significant moderators of the magnitude of genetic and environmental influences on antisocial behavior, but there were no significant differences in the magnitude of genetic and environmental influences for males and females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Production of androgenetic haploids in zebrafish with ultraviolet light

Anal cancer is more commonly found in homosexual and bisexual men than cervical cancer is in women. Invasive anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development of anal cancer. We characterized the prevalence and risk factors for ASIL in 346 HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of visible anal lesions, and human papillomavirus (HPV) tests were performed, and data on HIV serostatus, CD4 count, and medical and lifestyle history were collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV-positive men, the RR for ASIL increased with lower CD4 levels but was elevated even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared with HIV-negative men. High-level HPV infection, as measured by detection of both hybrid capture (HC) group A and group B types, was another significant risk factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV-negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV-negative men with anal HPV infection and HIV-positive men, regardless of CD4 level, are at high risk for ASIL.     

Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives

We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.     

Cancer incidence in a cohort of infertile women

Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.     

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.     

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.     

Long-term stability of communication deviance.

Communication deviance (CD), forms of communication that are not bizarrely thought disordered but are hard to follow and that make difficult the consensual sharing of attention and meaning, has been hypothesized as a nonspecific contributor of rearing parents to psychopathology of offspring, including schizophrenia. This hypothesis, or an alternative of genetic transmission, would gain plausibility if CD has long-term stability. CD was evaluated, using tape-recorded and reliably scored Rorschachs in 158 Finnish adoptees, and retested after a median interval of 11 years. Adolescent CD was not stably correlated with follow-up CD. However, initial CD at a mean age of 32 and follow-up CD were significantly correlated. Gender, genetic risk for schizophrenia, and DSM-III-R (American Psychiatric Association, 1987) psychiatric diagnoses had no effect on adult CD stability. CD appears to be a stable, traitlike feature of adult but not adolescent functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study

Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations are risk factors for coronary heart disease. We investigated environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertained families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether mendelian inheritance of a major gene could best explain the familial distributions of these 2 hemostatic factors. Age- and gender-adjusted familial correlations for PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to 0.21); the spouse correlation was positive but not statistically significant (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major gene associated with higher PAI-1 concentrations in 65% of individuals from these families. Demographic, anthropometric, lifestyle, and metabolic characteristics together explained 37% to 47% of the variation in PAI-1 antigen levels, and the inferred major gene explained an additional 17% of the variance. Positive and statistically significant age- and gender-adjusted familial correlations in first-degree relatives indicated a possible heritable component influencing plasma fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation analysis did not provide statistical evidence of a major gene controlling fibrinogen level. These family data suggest that there are modest familial and genetic effects on the concentration of PAI-1.     

Ebstein's malformation of the tricuspid valve: genetic and environmental factors. The Baltimore-Washington Infant Study Group

Ebstein's anomaly is a specific structural deformity of the tricuspid valve, and its rarity has hampered etiologic evaluation. Cases of Ebstein's anomaly registered in the Baltimore Washington Infant Study (BWIS), a regional case-control study of cardiovascular malformations (CVM) in infancy, are reviewed. Between 1981 and 1989 a total of 4,390 CVM cases, including 47 Ebstein cases, and 3,572 controls were registered. The prevalence of Ebstein's anomaly was 5.2 per 100,000 livebirths. Additional cardiac anomalies were present in 38.3% of Ebstein cases. Non-cardiac malformations were present in 19.1% of Ebstein cases vs. 25.5% of other CVM, and 1.7% of controls. Case-fatality by 1 year of age was 23.4% in Ebstein vs. 18.1% in other CVM. Interviews of parents of Ebstein cases, other CVM, and controls (n = 44, 3,335, and 3,572, respectively) elicited information on family history of malformations, maternal illnesses, reproductive history, therapeutic drugs, parental lifestyle, and environmental exposures during the periconceptional period. Case-control analyses suggest genetic, reproductive, and environmental risk factors: twins [odds ratio (OR) 8.2, 95% confidence interval (CI) 2.6-25.3]; family history of CVM (OR 6.4, 95% CI 1.8-22.2); white race (OR 2.9 with non-whites as reference, 95% CI 1.2-7.0); previous miscarriages (OR 2.0, 95% CI 1.2-3.3); maternal exposure to benzodiazepines (OR 5.4, 95% CI 1.5-19.1); and varnishing (OR 3.4, 95% CI 1.3-9.1). Additional multicenter investigations are warranted to elucidate the role of genetic, reproductive, and environmental factors in the etiology of this anomaly.     

Child and adolescent conduct disorder substantially shares genetic influences with three socioemotional dispositions.

In a representative sample of twin children and adolescents, we tested the hypothesis that a substantial proportion of the genetic and environmental influences underlying conduct disorder (CD) are shared with three socioemotional dispositions: Prosociality, Negative Emotionality, and Daring. Caretaker ratings of each dispositional dimension were uniquely associated with a latent CD dimension that included both caretaker- and youth-reports of CD as indicators. Behavior genetic analyses indicated that moderate-to-high additive genetic and moderate nonshared environmental influences underlie all three dispositions and CD, with modest shared environmental influences on Prosociality. Forty percent of the additive genetic influences and all of the nonshared environmental influences on the latent CD dimension were shared in common with the three socioemotional dispositions. The finding that CD shares a substantial proportion of its genetic influences with three distinct socioemotional dispositions suggests new perspectives on the heterogeneous etiology of CD and new approaches to exploring its specific etiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Industrial accidents are related to relative body weight: the Israeli CORDIS study

OBJECTIVES: The accident rate might be influenced by intrinsic characteristics of the workers, by risks inherent in the work environment, or a combination of these factors. As increased weight may be associated with sleep disturbances and fatigue, a high body mass index (BMI) might be an independent risk factor for accidents in industrial workers. METHODS: 3801 men were examined and followed up for two years for the occurrence of accidents. The objective environmental conditions were recorded and translated into a single score of ergonomic stress levels. Height and weight were recorded, as were possible confounding factors including measures of fatigue, type A personality, total night time sleep, job satisfaction, somatic complaints, smoking, and education levels. RESULTS: Both BMI and ergonomic stress levels independently predicted involvement in accidents (two or more) with those in the highest BMI quartile who worked in an environment with high ergonomic stress levels having a 4-6 times increased risk of accidents compared with those in the lowest BMI quartile who worked in an environment with low ergonomic stress levels (95% confidence interval (95% CI) 2.4-9.0, P < 0.001). Although increasing somatic complaints and a low educational level also were predictors of accidents, they did not mediate the effect of the BMI on the accident rate. Increasing age, less smoking, and decreased sleep hours were significantly associated with an increased BMI, but the association of BMI and involvement in accidents also could not be explained by those factors or the other confounders. CONCLUSIONS: BMI independently influences the accident rate. Further studies warranted to confirm these findings and to explore mechanisms supporting biological plausibility.     

Metals pollution in marine sediments of the United Arab Emirates creeks along the Arabian Gulf shoreline

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.     

Genetic and environmental influences on observed personality: Evidence from the German Observational Study of Adult Twins.

Previous behavior-genetic research on adult personality relied primarily on self-reports or peer reports that may be subject to contrast effects, resulting in biased estimates of genetic and environmental influences. In the German Observational Study of Adult Twins (GOSAT), personality traits of 168 monozygotic (MZ) and 132 dizygotic (DZ) twin pairs were rated on 35 adjective scales, largely markers of the Big 5. The ratings were provided by 120 judges who never met the twins but observed videotaped behaviors of 1 twin of each pair in 1 of 15 different settings. The aggregated video-based trait ratings were highly reliable, and substantial correlations were obtained between MZ as well as DZ twins. Model-fit analyses suggested about 40% genetic, 25% shared environmental, and 35% nonshared environmental influence. Extraversion was the only trait that seemed not to be influenced by shared environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The prevalence of non-insulin-dependent diabetes mellitus and the associated risk factors in a population of Mexico, D. F

Non-insulin-dependent diabetes mellitus (NIDDM) is a chronic disabling disease, that shortens length of life and implies a high burden for a community. Its prevalence goes from 0 per cent in Papua, New Guinea to 34 per cent in Pima Indians. There are very few prevalence studies in Mexico, and the strength of association of the known risk factors with the occurrence of the disease is not established. A prevalence cross sectional study was carried out with users of a first level medical care unit, with a meter measure of capillary glucose levels. Those with a previous diagnosis of diabetes or whose capillary glucose level were 200 mg or over were considered diabetics. Hyperglycemia was when the levels were recorded between 121 and 199 mg. The crude prevalence of NIDDM was 5.6 per cent (CI 95% 4.5-6.8), With almost no sex difference. Hyperglycemia prevalence was 2.9 per cent (CI 95% 2.0-3.7). Age was the main risk factor for the development of NIDDM. Those between 40 and 59 years showed a high risk (OR 10.8; CI 95% 5.4-22.0; p < 0.0001), and it was greater for the 60 years or elder (OR 20.6; CI 95% 9.8-44.1; p < 0.0001). Weight was also an important risk factor, with a 2.7 fold greater risk for obese persons (CI 95% 1.6-4.6; p < 0.0001). Other, risk factors were familiar history of diabetes (OR 1.5; CI 95% 0.9-2.3; p = 0.096), and overcrowding (OR 1.9; CI 95% 1.0-3.4; p = 0.03). In order to analyze independently each variable, a logistic regression model was applied, and a similar strength of association was observed for the crude model, but for obesity whose effect was modified by age. When only new cases were analyzed in the former model, the association with obesity was maintained. There is a need to develop prevalence studies of NIDDM in Mexico and to measure the strength of association with the known and the not jet well known risk factors of this disease in order to establish health policies according to the Mexican reality.     

Breastfeeding, maternal smoking and lower respiratory tract infections

The objective of the study was to assess the relationship between breastfeeding and lower respiratory tract infections (LRTIs) during the first year of life, with special reference to maternal smoking. A cohort of 3,754 children born in 1992-1993 in the City of Oslo, Norway was recruited and data were collected at birth, 6 and 12 months of age. Complete information was obtained from 3,238 children (follow-up rate 86%). The main outcome was an episode of a LRTI, such as pneumonia, bronchitis or bronchiolitis, based on a self-administered questionnaire addressed to parents when the child was 6 and 12 months old. The outcome was specified as physician-diagnosed. In logistic regression analysis adjusting for confounding, maternal smoking increased the risk of LRTIs in children breastfed for 0-6 months (odds ratio (AOR) 1.7; 95% confidence interval (95% CI) 1.2-2.4), but not essentially when the child was breastfed for more than 6 months (AOR 1.1; 95% CI 0.7-1.6). Short-term breastfeeding (0-6 months) and no maternal smoking was related to an adjusted AOR of LRTIs of 1.3 (95% CI 1.0-1.7), and short-term breastfeeding combined with maternal smoking was related to an adjusted AOR of 2.2 (95% CI 1.6-3.1), as compared with long-term breastfeeding and no maternal smoking. The present study indicates a protective effect of long-term breastfeeding on the risk of lower respiratory tract infection during the first year of life. The results suggest that the protective effect is strongest in children exposed to environmental tobacco smoke.     

Prosocial behavior from early to middle childhood: Genetic and environmental influences on stability and change.

Prosocial behavior is important for the functioning of society. This study investigates the extent to which environment shared by family members, nonshared environment, and genetics account for children's prosocial behavior. The prosocial behavior of twins (9,424 pairs) was rated by their parents at the ages of 2, 3, 4, and 7 and by their teachers at age 7. For parent ratings, shared environmental effects decreased from .47 on average at age 2 to .03 at age 7, and genetic effects increased from .32 on average to .61. The finding of weak shared environmental effects and large heritability at age 7 was largely confirmed through the use of teacher ratings. Using longitudinal genetic analyses, the authors conclude that genetic effects account for both change and continuity in prosocial behavior and nonshared environment contributes mainly to change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Risk for Separation Anxiety Disorder Among Girls: Paternal Absence, Socioeconomic Disadvantage, and Genetic Vulnerability.

The authors examined genetic and environmental influences, including the contributions of 2 measured aspects of the shared environment of twins (paternal absence, socioeconomic disadvantage) on the development of mother-reported separation anxiety disorder (SAD) history in a sample of 1,887 female twin pairs. Four different symptom categories of SAD were considered. Results revealed that all 4 SAD symptom categories were significantly heritable, whereas the contribution of shared environmental influences to the variation in risk was significant for only 2 of the 4 SAD categories. Paternal absence was found to have an important influence in vulnerability for SAD, whereas the effect of socioeconomic disadvantage was less robust. Evidence for race differences in the etiology of SAD was not found. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Segregation analysis reveals a major gene effect controlling systolic blood pressure and BMI in an Israeli population

It has been suggested that genetic factors control blood pressure level at all ages. However, the evidence is limited because of the composite nature of blood pressure and the heterogeneity of the studied samples. The purpose of the present study is to test for genetic influences on systolic blood pressure (SBP) level in a community-based Israeli family study. Segregation analysis was performed on 622 adults from 208 pedigrees. Age, sex, and body mass index (BMI) were significant covariates of SBP. Segregation analysis rejected the environmental transmission model but not the mixed Mendelian transmission model. The best-fitting genetic model was the mixed codominant model, with a heritability of 0.32 and an allele frequency of 0.18 for high SBP level. We further tested whether SBP and BMI shared a common major gene effect. Using bivariate segregation analysis involving two traits and a single locus, we found evidence for a single-locus pleiotropic effect on SBP and BMI. The allele frequency of this major locus was 0.24. The residual genetic correlation resulting from additive polygenes and the environmental correlation between these two traits were not different from zero after taking into account the shared major gene effect. The proportion of phenotypic variation attributable to this major gene effect increased with age for SBP but decreased with age for BMI.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.