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Biomedical subjects

P Lichtenstein

Publications and source records attributed to P Lichtenstein.

At least 37 records · Page 2Linked to original sources

Increased risks of circulatory diseases in late pregnancy and puerperium.

We studied a nationwide Swedish cohort with 654,957 women who had 1,003,489 deliveries from 1987 through September 1995 to assess late pregnancy and puerperal risks of circulatory diseases. We used standardized incidence rate ratios to calculate relative risks [with 95% confidence intervals (CIs)]. Compared with unexposed (nonpregnant and early pregnant) women, relative risks of venous thrombosis and pulmonary embolism during the third trimester were 6.7 (95% CI = 5.7--7.8) and 2.7 (95% CI = 1.7--4.2), respectively. Around delivery (from 2 days before to 1 day after delivery), the relative risks of all assessed circulatory diseases were dramatically increased: venous thrombosis, 115.1 (95% CI = 96.4--137.0); pulmonary embolism, 80.7 (95% CI = 53.9--117.9); subarachnoid hemorrhage, 46.9 (95% CI = 19.3--98.4); intracerebral hemorrhage, 95.0 (95% CI = 42.1--194.8); cerebral infarction, 33.8 (95% CI = 10.5--84.0); and myocardial infarction, 27.0 (95% CI = 0.6--180.0). During the rest of the first 6 weeks postpartum, the risks declined but were still substantially increased for all diseases, with the exception of subarachnoid hemorrhage. The results suggest that the increased risk for circulatory diseases related to pregnancy is mainly confined to a few days around delivery.

Adolescent↗

Genetic probes of three theories of maternal adjustment: I. Recent evidence and a model.

Studies focusing on genetic and social influences on maternal adjustment will illumine mother's marriage, parenting, and the development of psychopathology in her children. Recent behavioral genetic research suggests mechanisms by which genetic and social influences determine psychological development and adjustment. First, heritable, personal attributes may influence individuals' relationships with their family members. These genetically influenced family patterns may amplify the effects of adverse, heritable personal attributes on adjustment. Second, influences unique to siblings may be the most important environmental determinants of adjustment. We derive three hypotheses on maternal adjustment from integrating these findings from genetic studies with other contemporary research on maternal adjustment. First, mother's marriage mediates the influence of her heritable, personal attributes on her adjustment. Second, mother's recall of how she was parented is partially genetically influenced, and both her relationships with her spouse and her child mediate the impact of these genetically influenced representations on her current adjustment. Third, characteristics of mother's spouse are important influences on difference between her adjustment and that of her sister's. These sibling-specific influences are unrelated to mother's heritable attributes. The current article develops this model, and [figure: see text] the companion article describes the Twin Mom Study that was designed to test it as well, as its first findings. Data from this study can illumine the role of family process in the expression of genetic influence and lead to specific family interventions designed to offset adverse genetic influences.

Adaptation, Psychological↗

Genetic probes of three theories of maternal adjustment: II. Genetic and environmental influences.

This is the first report of the Twin Mom Study, an investigation of three hypotheses concerning influences on maternal adjustment. These hypotheses concern the role of the marital and parent-child relationships in mediating genetic influences on maternal adjustment and on the importance of the mothers' marital partners as a specifiable source of influences on their adjustment not shared with their sisters. The study's sample of 150 monozygotic (MZ) twins and 176 dizygotic (DZ) twins was drawn randomly from the Swedish Twin Registry and is, with some small exceptions, likely to be representative of women in the Swedish population. The sample included the marital partners of these twins and their adolescent children. Self-report and coded videotapes were a source of information about family process. Results reported in this first report focus on comparability of American and Swedish samples on scales measuring psychiatric symptoms, and on an analysis of genetic and environmental influences on nine measures of mothers' adjustment. Results suggest comparability between the US and Sweden. Genetic influences were found for all measures of adjustment, particularly in the psychological manifestations of anxiety and for smoking. The pattern of findings also underscored the importance of influences unique to each sibling within the twin pair, thus focusing attention on the potential role of marital partners in maternal adjustment. Results also suggested that experiences shared by the twin sisters, experiences unrelated to their genetic similarity, may influence their fearfulness and alcohol consumption. Our model did not include these influences and thus must be amended.

Adaptation, Psychological↗

Tall or short? Twenty years after preeclampsia exposure in utero: comparisons of final height, body mass index, waist-to-hip ratio, and age at menarche among women, exposed and unexposed to preeclampsia during fetal life.

Women exposed to preeclampsia during fetal life have lower risk of breast cancer, compared with unexposed women, possibly through fetal programming. Hypothetically, preeclampsia exposure could affect well-known risk factors for breast cancer, such as pubertal development or adult anthropometry. Women born in a defined geographic area of Sweden from 1973 through 1978, with verified preeclampsia exposure (n = 230) and nonexposure (n = 359) during fetal life, answered questions about anthropometric measures, smoking, parity, and age at menarche in a telephone interview in early adulthood. Compared with unexposed offspring, female offspring of women who had preeclampsia were lighter and shorter for gestational age, but in young adulthood there were no differences in height, body mass index, waist-to-hip ratio, or age at menarche. When analyzing the effects of other maternal and fetal characteristics, the results indicate that approximately 50% of the variance in final height was explained by parental heights and birth length for gestational age. Young-adult body mass index was weakly associated with maternal body mass index, maternal smoking, and birth weight for gestational age, which together explained 12% of the variance. Neither of the assessed maternal or fetal characteristics were significantly associated with age at menarche or waist-to-hip ratio. These data indicate that neither adult anthropometry nor age at menarche is in the causal pathway between intrauterine preeclampsia exposure and the reduced risk of breast cancer.

Adolescent↗

Heritability of cervical tumours.

Development of cervical cancer is strongly associated with genital infection of oncogenic types of human papillomavirus (HPV). However, the majority of women infected with HPV never develop cancer; thus, additional factors appear to be necessary. The relative importance of genetic and environmental factors to the development of cervical tumours is not known. Therefore, we have estimated the heritability of liability to this disease. The Swedish Cancer Register and the National Family Register were used to identify biological and adoptive mothers and full, half- and adoptive sisters of cases with cervical tumours, as well as age-matched controls. Tetrachoric correlations were calculated and model fitting techniques used to estimate the relative importance of shared genes and shared familial environment. Shared genes (heritability) explain 27% (95% CI 26%-29%) of the total variation in liability to the disease. A significant effect of shared familial environment was seen among sisters but not among mother/daughter relations. Sister-specific shared environment accounts for 2% (95% CI 1%-4%) of the variance. Our results indicate that development of cervical tumours depends, to a significant extent, on inherited genetic factors. Genetic predisposing factors may influence the likelihood of, sensitivity to or persistence of HPV infection, as well as the rate of tumour development.

Cohort Studies↗

Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland.

BACKGROUND: The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. METHODS: We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. RESULTS: At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). CONCLUSIONS: Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites suggests major gaps in our knowledge of the genetics of cancer.

Adult↗

Genetic effects on the liability of developing pre-eclampsia and gestational hypertension.

Genetic factors are known to be important in the etiology of pre-eclampsia and possibly also gestational hypertension, but the degree of genetic influence has not been quantified. To estimate the genetic and environmental effects on the liability of developing pre-eclampsia and gestational hypertension, we cross-linked the population-based Swedish Twin Register and the Swedish Medical Birth Register. We included female twin pairs with known zygosity, both of whom gave birth in Sweden from 1973 through 1993; in all 917 monozygotic and 1,199 dizygotic twin pairs. For pre-eclampsia, the estimates of heritability and nonshared environmental effect were 0. 54 (95% confidence interval 0-0.71) and 0.46 (0.29-0.67), respectively; corresponding estimates for gestational hypertension were 0.24 (0-0.53) and 0.76 (0.47-1.00), respectively. When considering both diseases as a single entity (pregnancy-induced hypertensive diseases), the heritability estimate was 0.47 (0.13-0. 61). These results suggest that genetic factors are important in the development of pre-eclampsia as well as gestational hypertension. The heritability estimates can be of importance when planning genetic linkage studies. In efforts to identify women with elevated risk of developing pre-eclampsia during pregnancy, a question about family history of pre-eclampsia should be included.

Adolescent↗

Parents' perception of mental development and behavioural problems in 8 to 9-year-old children.

UNLABELLED: A slow maturational rate may be an underlying antecedent of a psychiatric disorder. If this is correct, differences in behavioural problems could be related to the maturity level in children of the same chronological age. The aim of the study was to compare the parents' perceptions and assessments of their children's maturational status and behavioural problems. A population based on a nationwide sample from the Swedish twin-register of 8 to 9-y-old children (n = 1079) was used. The parents completed a questionnaire including their views on their child's maturity level, the Swedish version of the Child Behaviour Checklist (CBCL) and an Attention Deficit Hyperactivity Disorder (ADHD) checklist based on the DSM-III-R criteria. Multivariate analyses showed a statistically significant relationship between immaturity reported by the parents and several behavioural problems reported on the CBCL: somatic complaints, anxious and depressed, social problems, thought problems, attention problems, behaviour problems and aggressive behaviour. There was also a statistically significant relationship between the maturity factor and the CBCL grouping of syndromes (internalizing, externalizing, total behaviour problems score) as well as between the maturity factor and ADHD. CONCLUSION: We conclude that at least from the parents' point of view the behaviour problems in their children may be related to maturity.

Adult↗

Genetic influence on birthweight and gestational length determined by studies in offspring of twins.

OBJECTIVE: To determine the relative importance of genetic effects on birthweight, gestational length and small for gestational age. DESIGN: A cohort study, using individual record linkage between the population-based Swedish Twin and Birth Registers to estimate twin similarities in twins with known zygosity. POPULATION: Included were 868 monozygotic and 1141 dizygotic female twin pairs, born in Sweden before 1959, who both delivered single births from 1973-1993. METHODS: Quantitative genetic methods, offspring birthweight, gestational length and small for gestational age birth in twin sisters. MAIN OUTCOME MEASURES: Twin similarities measured as probandwise concordance rates and intra-class correlations for birthweight, gestational length and small for gestational age births. RESULTS: Concordance rates and intra-class correlations for birthweight, gestational length and small for gestational age were consistently higher in monozygotic compared with dizygotic twins. Model fitting suggested heritability estimates in the range from 25% to 40%. CONCLUSIONS: This study suggests genetic effects not only for birthweight and fetal growth, but also for gestational length. The mediation of these genetic effects may partly be due to similarities in maternal antropometric measures, lifestyle and medical complications during pregnancy. The study does not distinguish between fetal and maternal genetic effects.

Birth Weight↗

Aetiology of teenage childbearing: reasons for familial effects.

The aims of the present study were to evaluate the contribution of the genetic and environmental factors to the risk of teenage childbearing, and to study whether life style, socio-economic conditions, and personality traits could explain possible familial effects. We linked two population-based registers: the Swedish Twin Register and the Swedish Medical Birth Register. The study covers female twin pairs born between 1953 and 1958, having their first infant before the age of 30 years (n = 1885). In order to separate familial effects from other environmental influences, and genetic effects from shared environmental effects, only complete twin pairs with known zygosity were included, in all 260 monozygotic and 370 dizygotic twin pairs. We used quantitative genetic analyses to evaluate the importance of genetic and environmental effects for liability to teenage childbearing. Logistic regression analyses were used to estimate the effects of life style, socio-economic situation, and personality on the probability of teenage childbearing, and to study whether psychosocial factors could explain possible familial effects. Fifty-nine percent (0-76%) of the variance in being a teenage mother was attributable to heritable factors; 0% (0-49%) was due to shared environmental factors; and 41% (23-67%) was explained by non-shared environmental factors. Thus, the data were consistent with the hypothesis that the familial aggregation of teenage childbearing is completely explained by genetic factors, although the alternative hypothesis that familial aggregation is entirely explained by shared environmental factors cannot be ruled out. Significant effects of smoking habits, housing conditions, and educational level were found in relation to liability to teenage childbearing. However, the familial effects on risk of teenage childbearing were not mediated through similarities in life style and socio-economic factors. When studying risk factors for teenage childbearing, it is recommended to include life style and socio-economic variables as well as information about family history of teenage childbearing. Twin Research (2000) 3, 23-27.

Adolescent↗

Heritability and prevalence of specific fears and phobias in childhood.

Fears and phobias are relatively common in childhood. Both environmental and genetic theories have tried to explain the etiology behind these conditions. However, data supporting the different theories are sparse. To investigate the relative importance of genetic and environmental influences on specific phobias and fears, parental reports of animal, situational, and mutilation fears and phobias were completed for 1106 pairs of 8- to 9-year-old Swedish twins. The prevalence of specific phobias was 7.3% for boys and 10.0% for girls. Genetic. shared environmental, and nonshared environmental effects contributed to individual differences in fears and phobias in young children, but the magnitude of the effects differed between sexes. Shared environmental effects contributed to a general susceptibility for fearfulness. Genetic and nonshared environmental effects, on the other hand, contributed both to the general susceptibility and specific fearfulness, even though these effects primarily were fear specific. These results indicate that both heritable factors as well as environmental factors such as trauma, vicarious learning, and/or negative information are important for differences in fearfulness and phobias--at least in children.

Age Distribution↗

DNA copy number losses at 1p32-pter in monozygotic twins concordant for breast cancer.

To find similarities that may possibly indicate novel mutations, we performed comparative genomic hybridization (CGH) analysis following degenerate oligonucleotide primed polymerase chain reaction (PCR) for DNA obtained from unique material of breast cancer that developed in monozygotic twin-pairs. Polymerase chain reaction amplification was successful in 12 samples for 11 patients, including 3 pairs. Six samples exhibited DNA copy number changes. Gains (76%) were more frequent than losses (24%). Gains or high-level amplifications in 8q were present in all but 1 of the abnormal cases. Frequent gains were detected with a minimal common overlapping region at 5p (4 cases), at 1q25-qter (3 cases), and at 20q12-qter (2 cases). The most frequent loss, detected in half of the abnormal cases, was at 1p32-pter. One twin-pair showed similar changes in 4 chromosomal locations involving loss of 1p32-pter and gains in 1q25-qter, 5, and 8q.

Base Sequence↗

Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry.

Case-control studies of lifestyle factors have been inconclusive in the study of endometrial cancer, and prospective data are scarce. Our aim was to examine the associations of physical activity, weight and weight change, fruit, vegetable, and alcohol consumption, socio-economic status, parity and presence of diabetes mellitus with the risk of endometrial cancer in a cohort study. In 1967, 11,659 women in the Swedish Twin Registry, born 1886-1925, answered a 107-item questionnaire, including questions about diet, physical activity and other lifestyle factors. Complete follow-up through 1992 was attained through record linkage to the Swedish Cancer and Death Registers. The relative risks for endometrial cancer were estimated in proportional hazards models that adjusted confidence limits for correlated outcomes. We observed 133 incident cases of endometrial cancer in the cohort. There was no clear pattern of risk over strata of alcohol or fruit and vegetable intake, although the data suggest an increased risk with very low fruit and vegetable intake. Increasing physical activity markedly decreased the risk of endometrial cancer (p for trend < 0.01), independently of weight and parity; the risk in the highest quartile, relative to the sedentary category, was 0.2 (95% CI 0.3-0.8). As expected, higher weight in middle age increased the risk (p for trend < 0.01), as did higher weight in early adulthood. Contrary to previous findings, weight gain did not have an effect independent of weight at enrollment. We did not find a genetic component to endometrial cancer. Our results confirm that environmental factors are the most important, especially physical activity, parity, and weight in young and middle age.

Adult↗

Genetic and environmental influences on recurrent headaches in eight to nine-year-old twins.

The major objective of the present study was to estimate genetic and environmental influences on recurrent headaches in prepubescent twins. A nationwide cohort of 8 to 9-year-old Swedish twins (n = 1,480) was screened for nonsymptomatic and recurrent headaches through a questionnaire mailed to their parents (75% response frequency). Among positives, 79% of headaches were classified as migraine or tension-type headache in close accordance with the International Headache Society criteria. The prevalences of migraine and nonmigrainous headaches were 2.4% and 11.3%, respectively, and without significant differences between the sexes or zygosity types. Inheritance on liability to recurrent headaches was estimated to 70% (a2 = 0.70, 95% CI = 0.54-0.82) for boys and girls but the genetic effect was found to be uncorrelated between the sexes. We conclude that genetic and individual specific effects are important for recurrent headaches of migrainous and nonmigrainous types in prepubescent children, and that different genetic etiologies might exist for boys and girls.

Child↗

A twin study of mortality after spousal bereavement.

BACKGROUND: Previous research has shown an increased risk of mortality after spousal bereavement, with the highest risk in the first weeks or months closest to the loss. One difficult issue in these designs is appropriate covariates and control groups. METHOD: This study is based on 1993 pairs of twins discordant for marital status and on 35860 married individuals from the Swedish Twin Registry born between 1886 and 1958 and followed for marital and vital status between 1981 and 1993. RESULTS: Spousal bereavement was a risk factor for mortality for both men and women using the still married co-twin as a control to the widowed proband, and controlling for earlier health status and health-related risk factors. The mortality risk was higher for young-old (under 70 years) individuals, and for recently widowed than for longer-term widowed. Young-old women had a pattern with increased mortality risk during the first years after bereavement, but also a markedly decreased risk if they survived 4 years after bereavement, as compared to married women. CONCLUSIONS: The results support a causal effect of bereavement on mortality. The decrease in risk for long-term young-old women is congruent with reports by widows of psychological growth after bereavement, involving increased sense of mastery and competence after learning to live in new sets of circumstances following the loss of their husband.

Adult↗

Hypospadias is related to birth weight in discordant monozygotic twins.

PURPOSE: Hypospadias is a common urogenital malformation in boys. The etiology is unknown but genetic and environmental factors are involved. Because monozygotic twins have the same genetic constitution, we studied disease discordant twin pairs to evaluate environmental risk factors while controlling for genetic effects. MATERIALS AND METHODS: We used questionnaires to identify 28 male twins discordant for hypospadias at 4 pediatric surgical clinics in Sweden. Using deoxyribonucleic acid fingerprinting, and histopathological examination of the placenta and fetal membranes 18 twin pairs were diagnosed as monozygotic. RESULTS: In 16 of the 18 monozygotic pairs discordant for hypospadias the twin with the lowest birth weight has hypospadias. Mean difference in birth weight was 498 gm. (t = 3.8, p <0.01). CONCLUSIONS: Environmental factors associated with low birth weight are involved in the etiology of hypospadias.

Birth Weight↗

No paternal effect on monozygotic twinning in the Swedish Twin Registry.

Previous research has provided evidence for a genetic effect in monozygotic twinning, indicated by an increased risk for monozygotic women to have monozygotic offspring. However, since the biological mechanism for this trait is unknown, it is not clear if there exists a paternal inheritance. In this study we investigated twin pregnancies in offspring born in 1941-1996 to male twins in the Swedish Twin Registry and population controls born in 1926-1980. In total 4,225,331 offspring, of which 89,286 were twins, were studied. There was neither an increase in the probability for monozygotic men to have like-sexed twin offspring risk ratio (RR = 0.95; 95% CI = 0.77-1.13) nor an increase in the estimated number of monozygotic twin births. Thus, there is no evidence for a paternal effect on monozygotic twinning, suggesting that the gene(s) increasing the liability for division of the embryo are expressed in the mother and not in the fertilised egg.

Cohort Studies↗