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P Lichtenstein

Publications and source records attributed to P Lichtenstein.

At least 19 recordsLinked to original sources
PubMed2006

Estimation of genetic and environmental factors for melanoma onset using population-based family data.

Estimation of genetic and environmental contributions to cancers falls in the framework of generalized linear mixed modelling with several random effect components. Computational challenges remain, however, in dealing with binary or survival phenotypes. In this paper, we consider the analysis of melanoma onset in a population of 2.6 million nuclear families in Sweden, for which none of the current survival-based methodologies is feasible. We treat the disease outcome as a binary phenotype, so that the standard proportional hazard model leads to a generalized linear model with the complementary-log link function. For rare diseases this link is very close to the probit link, and thus allows the use of marginal likelihood for the estimation of the variance components. We correct for the survival length bias by censoring the parent generation within each family at the time they attain the same cumulative hazard as the child generation, thus improving the validity of the estimates. Our finding that childhood shared environment in addition to genetic factors had a considerable effect on the development of melanoma is consistent with epidemiological studies.

Adolescent↗
PubMed2005

Is Swedish snus associated with smoking initiation or smoking cessation?

Nicotine replacement therapies (NRT) are an effective treatment for tobacco dependence, yet most smokers do not quit or remain abstinent. We investigated whether Swedish snus (snuff) use was associated with smoking cessation among males participating in a large population based twin study in Sweden. Snus use was associated with smoking cessation but not initiation. Given that snus delivers comparable nicotine concentrations but carries lesser cancer risk than cigarettes, snus may be a widely used, non-medical form of NRT. Evaluation of the efficacy of snus for smoking cessation should be evaluated in randomised clinical trials.

Adult↗
PubMed2004

Low birthweight and Type 2 diabetes: a study on 11 162 Swedish twins.

BACKGROUND: To investigate the association between low birthweight and diabetes in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed Swedish twins born between 1906 and 1958 was used in order to investigate the risk of developing Type 2 diabetes between and within twin pairs by utilizing random effects linear models. RESULTS: Between pairs there was a significant increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P = 0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of the heterogeneity of the within and between effects showed no significant difference between the estimates. CONCLUSIONS: The study suggests that reduced fetal growth increase the risk of Type 2 diabetes due to an in utero programming effect possibly caused by intrauterine malnutrition. However, it does not exclude the possibility of a common genetic mechanism.

Adult↗
PubMed2004

Estimation of genetic and environmental factors for binary traits using family data.

While the family-based analysis of genetic and environmental contributions to continuous or Gaussian traits is now straightforward using the linear mixed models approach, the corresponding analysis of complex binary traits is still rather limited. In the latter we usually rely on twin studies or pairs of relatives, but these studies often have limited sample size or have difficulties in dealing with the dependence between the pairs. Direct analysis of extended family data can potentially overcome these limitations. In this paper, we will describe various genetic models that can be analysed using an extended family structure. We use the generalized linear mixed model to deal with the family structure and likelihood-based methodology for parameter inference. The method is completely general, accommodating arbitrary family structures and incomplete data. We illustrate the methodology in great detail using the Swedish birth registry data on pre-eclampsia, a hypertensive condition induced by pregnancy. The statistical challenges include the specification of sensible models that contain a relatively large number of variance components compared to standard mixed models. In our illustration the models will account for maternal or foetal genetic effects, environmental effects, or a combination of these and we show how these effects can be readily estimated using family data.

Cluster Analysis↗
PubMed2003

Birth weight and risk of angina pectoris: analysis in Swedish twins.

OBJECTIVE: Intrauterine nutrition approximated by birth weight has been shown to be inversely associated with risk of coronary heart disease (CHD). By investigating the association within twin pairs discordant for disease, the influence of genetic and early environmental factors is substantially reduced. METHODS: We have investigated the association between birth weight and angina pectoris in same-sexed twins with known zygosity included in the population-based Swedish Twin Registry. Self-reports of birth weight and angina pectoris were collected in a telephone interview between 1998 and 2000. The cohort analyses were based on 4594 same-sexed twins, and the within-pair analyses included 55 dizygotic and 37 monozygotic twin pairs discordant for angina pectoris. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. RESULTS: Compared with birth weight between 2.0 and 2.9 kg, low birth weight (<2.0 kg) was associated with increased risk of angina pectoris in the twin cohort, (OR: 1.46; 95% CI: 1.14-1.87), but after adjustment for potential confounders the risk decreased, and did not reach significance. Within twin pairs discordant for angina pectoris, low birth weight was significantly associated with increased risk of angina pectoris within dizygotic twins (adjusted OR: 5.73; 95% CI: 1.59-20.67), but not within monozygotic twins (adjusted OR: 1.20; 95% CI: 0.40-3.58). CONCLUSIONS: The results suggest that genetic differences associated with foetal growth and adult risk of CHD may have affected previously reported associations between birth weight and CHD.

Aged↗
PubMed2002

The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies.

The Swedish Twin Registry (STR), which today has developed into a unique resource, was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases whilst controlling for genetic propensity to disease. Since that time, the Registry has been expanded and updated on several occasions, and the focus has similarly broadened to most common complex diseases. In the following, we will summarize the content of the database, describe for the first time recent data collection efforts and review some of the principal findings that have come from the Registry.

Cohort Studies↗
PubMed2001

Variation in genetic and environmental influences in serum lipid and apolipoprotein levels across the lifespan in Swedish male and female twins.

The contribution of genetic and environmental factors to variation in lipids and apolipoproteins has been estimated in previous twin and family studies. However, it is unclear whether there are sex and/or age differences in parameter estimates. We investigated a sample selected from the population-based Swedish Twin Registry of 725 like- and unlike-sex twin pairs, ages 17-85. Quantitative genetic methods were used to evaluate sex and age differences in genetic and environmental variation in lipid and apolipoprotein levels in three age groups, 17-49, 50-69, and 70-85. Heritabilities for lipids and apolipoproteins ranged from 35%-74%. Consistent sex differences were found in triglycerides. Females had higher heritabilities (56%) than males (35%) across the age groups. Total phenotypic variation increased across the age groups for cholesterol and apolipoprotein B due to an increase in unique environmental variance components. In contrast, in apolipoprotein A1 variance was highest in the middle age group and no differences were found in the phenotypic variance between age groups for triglycerides. We concluded that differences in phenotypic variation for cholesterol and apolipoprotein B were almost entirely due to the accumulation of environmental experiences throughout life, whereas there were no consistent patterns of differences in phenotypic variance for apolipoprotein A1 and triglycerides.

Adolescent↗
PubMed2001

Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarction.

BACKGROUND: Epidemiological studies that used birthweight as a crude marker of fetal growth have suggested that low birthweight is associated with increased risk of coronary heart disease. Through investigation of this association within same-sexed twin pairs, confounding by genetic and early environmental factors can be greatly decreased. We undertook a case-control study in twins discordant for acute myocardial infarction (AMI). METHODS: The case-control study was nested within the population-based Swedish Twin Registry and linked with the national cause-of-death and hospital-discharge registries. We manually retrieved birth records containing information on birth and maternal characteristics for 132 same-sexed twin pairs discordant for AMI and 118 individually matched control twin pairs. FINDINGS: In comparisons between AMI cases and external matched control twins, cases had significantly lower birthweight (mean 2556 [SD 500] vs 2699 [530] g, p=0.04), birth length (47.1 [2.8] vs 47.9 [2.7] cm, p=0.04), and head circumference (33.0 [1.8] vs 33.5 [2.0] cm, p=0.03) than controls. In within-pair comparisons between AMI cases and healthy co-twins, no significant differences in birth measurements were found (birthweight 2458 [510] vs 2534 [530] g, p=0.73; birth length 47.1 [2.8] vs 47.2 [2.8] cm, p=0.91; head circumference 33.0 [1.7] vs 33.0 [1.8] cm, p=0.92). INTERPRETATION: The lack of an association between birth characteristics and AMI within twin pairs suggests that previously reported associations may be influenced by genetic and early environmental factors, or possibly, by unmeasured maternal factors that operate independently of birthweight.

Birth Weight↗
PubMed2001

Fatty fish consumption and risk of prostate cancer.

Consumption of fatty fish might reduce the risk of prostate cancer, although epidemiological studies of fish consumption are rare. We studied the association between fish consumption and prostate cancer in a population-based prospective cohort of 6272 Swedish men. During 30 years of follow-up, men who ate no fish had a two-fold to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts did. Our results suggest that fish consumption could be associated with decreased risk of prostate cancer.

Adult↗
PubMed2001

[Swedish twin study surveys how antisocial behavior is developed. Hereditary factors are more important in girls, in older children and in aggressive behavior].

During the 20th century, political opinions and scientific theories rather than scientific results have incited swings in public discourse concerning the origin of criminal and other behaviors. Twin-studies, adoption-studies and animal studies have shown that both genes and environmental factors are important. A longitudinal study of all twins in Sweden born between May 1985 and December 1986 has been initiated to examine how genes and environmental factors influence the development of, inter alia, antisocial behavior. The study has shown that genetic factors in antisocial behavior are more important in girls, in aggressive behavior, and in older children. Further, genes and environmental factors of importance in childhood were important also in early adolescence.

Adolescent↗
PubMed2001

Physical activity and risk of renal cell cancer.

The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.

Aged↗
PubMed2001

Long-term tobacco smoking and colorectal cancer in a prospective cohort study.

Tobacco smoking has consistently been associated with colorectal adenomas, precursors of cancer, but the association with colorectal cancer itself has not been consistent. If colorectal cancer emerges only after a 35-year induction period, an association would unlikely be detected in studies where exposure assessment is of shorter duration. Most previous studies do not examine smoking of such duration and therefore do not account for the hypothesized 35-year induction period. By using the Cox proportional hazards models to estimate relative risks, we studied the association of long-term smoking and colorectal cancer risk in a population-based prospective cohort of 17,118 Swedish twins with up to 30 years of follow-up and information on smoking habits prior to baseline exposure assessment. Long-term heavy smoking was associated with a statistically significant 3-fold increased risk of colorectal cancer compared with never smoking (relative risk 3.1, 95% CI 1.4- 7.1). Examining colorectal cancer sub-sites separately, a non-significant 60% increased risk of colon cancer was observed only for heavy smokers and a statistically significant 5-fold increased risk was observed for rectal cancer. Our data lend some support to the hypothesis that heavy long-term cigarette smoking is associated with increased risk of colorectal cancer. Further elucidation of this association would be valuable from both etiologic and public health perspectives.

Adult↗
PubMed2001

Birth characteristics and breast cancer risk: a study among like-sexed twins.

High birth weight has been proposed to increase the risk of breast cancer. Birth weight and gestational age are positively associated with intrauterine estrogen exposure, which may initiate the carcinogenic process in mammary gland tissue and determine mammary gland cell mass later in life. In the present case-control study, we retrieved birth records for 96 female twin pairs where one twin had developed breast cancer. We used two control groups. In the external comparison, we used aged-matched twins as the control group, and in the within-pair comparison the control group included the healthy twin sisters. Odds ratio (OR) was used to estimate the relative risk, using 95% confidence intervals (CI). Compared with twins with gestational age less than 33 weeks, twins with gestational age of more than 40 weeks were at increased risk of breast cancer (OR = 8.4; 95% CI 1.3-54.4). In the within-pair comparison, mean birth weight and ponderal index were higher among cases compared with their co-twins (p = 0.07 and p = 0.05, respectively). The risk of breast cancer increased with birth weight. Compared with women with birth weight of less than 2,000 g, women with birth weight of at least 3,000 g had a nonsignificant increase in risk of developing breast cancer (OR = 3.5; 95% CI 0.7-18.5). The results give some support to the hypothesis that the fetal environment influences adult breast cancer risk.

Adult↗
PubMed2001

Estimation of genetic and environmental components in colorectal and lung cancer and melanoma.

Cancer has predominant environmental and somatic causes but the assessment of hereditary (genetic) causes is difficult, except for highly penetrant single-gene causes. Family studies are only partially informative in this regard because family members share diet and life-styles. Twin studies have been classically used to disentangle the effects of heredity and environment on disease etiology. We estimate the genetic and environmental components in colorectal and lung cancer and melanoma by comparing cancer risks in family members. The Swedish Family-Cancer Database, comprising more than 6 million individuals, was used as the source of family and cancer data. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modelling was used to derive estimates of the importance of genetic and environmental effects. The estimated genetic component ranged from 10% in colon and colorectal cancer to 18% in melanoma. For lung cancer, the share was 14%. If assortative mating were important for liability to cancer, these heritability estimates may be an underestimation of the true genetic effects. Non-shared environmental effect was 67-68% in colorectal cancer and melanoma, and 71% in lung cancer. Shared and childhood environments were equally important in colorectal cancer and melanoma, whereas no childhood effect was observed for lung cancer.

Adolescent↗
PubMed2001

Allelic imbalance on chromosomes 13 and 17 and mutation analysis of BRCA1 and BRCA2 genes in monozygotic twins concordant for breast cancer.

To study genetic changes associated with the development of breast cancer and the extent of its hereditary predisposition, paraffin-embedded tissue samples were obtained from monozygotic twin pairs concordant for breast cancer through the linked Swedish Twin and Cancer Registries. DNA samples extracted from the matched tumour and normal tissues of nine twin pairs were analysed for allelic imbalance using a series of microsatellite markers on chromosomes 13 and 17, containing loci with known tumour suppressor genes. Multiple losses of constitutional heterozygosity (LOH), consistent with a loss of large genomic region, the whole chromosome or chromosome arm, was found in at least three pairs of twins. One double mitotic crossover was identified in one tumour sample in a pair concordant for LOH at multiple loci on both chromosomes. Recombination breakpoints were mapped to regions delineated by D13S218 and D13S263, and D13S155 and D13S279, respectively. In general, no genetic effect of losing the same allele within a twin pair was found. However, for one marker at chromosome 13 (D13S328, between the BRCA2 and the RB-1 loci) and two markers on chromosome 17 (D17S786, distal to the p53 locus, and D17S855, an intragenic BRCA1 marker) the proportion of twin pairs with the same LOH was significantly higher than expected. These regions may reflect hereditary genomic changes in our sample set. In addition, tumour DNA samples from a subset of 12 twin pairs were analysed for BRCA1 and BRCA2 mutations using exon-by-exon single-strand conformation polymorphism analysis. Two unclassified BRCA2 variants, with a putative pathogenic effect, were identified, but no pathogenic alterations were found in the BRCA1 gene.

Adult↗
PubMed2001

Age and sex differences in genetic and environmental factors for self-rated health: a twin study.

OBJECTIVES: Self-rated health has been shown to be a predictor for future health status and mortality. The purpose of this study was to investigate age-group and sex differences in genetic and environmental sources of variation for self-rated health. METHODS: A sample of twins from the Swedish Twin Registry participated in a computer-assisted telephone interview with assessment of self-rated health. Structural equation model analyses on 1,243 complete twin pairs provided estimates of genetic and environmental components of variance. RESULTS: Individual differences primarily reflected individual specific environmental influences at all ages. The increase in total variance across age groups was primarily due to genetic influences in the age groups 45--74 years and greater environmental influences in the oldest age group (>74). No significant sex differences were found in variance components. DISCUSSION: Genetic variance in the two middle age groups (45--74) could reflect genetic susceptibility to age-dependent illnesses not yet expressed in the youngest group. The findings suggest that it might be more fruitful to explore the origins of individual differences for self-rated health in the context of an individual's age and birth cohort rather than in the context of sex.

Adolescent↗