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Biomedical subjects

N L Pedersen

Publications and source records attributed to N L Pedersen.

At least 73 records · Page 4Linked to original sources

The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry.

BACKGROUND: The relative importance of genetic influences on longevity was studied on data from the population-based Swedish Twin Registry. METHODS: A sample of 3,656 identical and 6,849 like-sexed fraternal twin pairs was studied regarding mortality rates and within-pair similarity for age at death. Genetic and environmental contributions to variation in longevity, expressed by integrated mortality rates, were estimated from a subsample of 1,734 twin pairs reared together and 130 twin pairs reared apart from the cohorts born 1886 to 1900. RESULTS: The intraclass correlation coefficients suggested that the genetic effect was small, and, for males, perhaps absent. Among pairs in which both twins died relatively young and among pairs in which both twins lived until very old age, the variance in age at death seemed to have no genetic component. Model fitting procedures based on twins reared apart and twins reared together indicated that most of the variance in longevity was explained by environmental factors. CONCLUSIONS: Over the total age range examined, a maximum of around one third of the variance in longevity is attributable to genetic factors, and almost all of the remaining variance is due to nonshared, individual specific environmental factors. The evidence that genetic factors play a minor role depending upon age at death merits further examination.

Adult↗

Longitudinal and genetic effects in the relationship between pulmonary function and cognitive performance.

Previous studies have found cognitive deficits in patients with impaired pulmonary function, and recent data from healthy older adults suggest an association of pulmonary function with cognitive function. This 6-year longitudinal study evaluated genetic and environmental sources of covariation in the association of pulmonary function and cognitive performance. The sample included 222 Swedish twin pairs (60% women) with a mean age of 62.3 (+/- 7.7) years (age range: 40-84). Hierarchical multiple regression analyses, controlling for the effects of age, gender, and height, were employed to predict performance on cognitive tests of fluid intelligence (Digit Symbol, Block Design, Digit Span-Backward) and crystallized intelligence (Information) from forced expiratory volume in one second (FEV1). Bivariate cross-twin correlations were used to evaluate the contribution of genetic and environmental factors in the association of pulmonary function and cognitive performance. Results indicated that FEV1 predicted performance on tests of fluid intelligence but not crystallized intelligence at the initial assessment and at the 6-year follow-up. Cross-twin correlational analyses indicated that genetic effects accounted for a greater share of the association of pulmonary function and cognitive performance than environmental effects, but environment also accounted for a substantial share of the covariance.

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↗

Self-rated health among cardiovascular drug users in a study of Swedish twins.

The aim of this study was to analyse the relationship between self-perceived health and cardiovascular disease with and without drug treatment. Mental health and genetic effects were controlled for in the analyses. The data for these analyses were collected in 1984 as part of the Swedish Adoption/Twin Study of Aging (SATSA). In the first set of analyses, 1147 persons (mean age 60 years, 72% older than 50 years) were included. In the second part of the study, twin pairs discordant with respect to having a cardiovascular disease and/or drug use were included in the analyses. Cardiovascular disease was related to poor, self-rated health among both men and women. The proportion with bad health was largest among those with a drug-treated disease. In multivariate analyses, a strong relationship between cardiovascular disease, drug therapy and low self-rated health remained after controlling for mental health. The co-twin control analyses indicate that cardiovascular drugs have at most a marginal negative effect on health beyond the effects of the disease and genetic liability to self-perceived poor health.

Adult↗

Multivariate genetic analysis of the causes of temperance board registrations. In all Swedish male-male [correction of male-female] twin pairs born 1926-1949.

BACKGROUND: The Temperance Boards in Sweden registered individuals for three reasons: public drunkenness, driving under the influence of alcohol and committing a crime in connection with alcohol. We wanted to ascertain whether these three forms of alcohol-related problems result from similar or different genetic and environmental risk factors. METHOD: We conducted a trivariate twin analysis of these three causes of registration in all male-male [corrected] twin pairs of known zygosity born in Sweden, 1926-1949 (n = 5177 twin pairs). RESULTS: Prevalences of registration for public drunkenness, drink-driving and alcohol-related crime were, respectively, 9.0, 3.6 and 4.0%. The best-fitting model had one general genetic and one general familial-environmental factor with specific genetic risk factors for drink-driving and specific familial-environmental risk factors for alcohol-related crime. CONCLUSIONS: The three causes for alcohol registration in Sweden largely reflect the same genetic and environmental risk factors. Estimated heritabilities were similar for the three forms of registration. However, specific genetic risk factors exist for drink-driving and specific familial-environmental risk factors for alcohol-related crime. Genetic factors are somewhat less important and familial-environmental factors more important for public drunkenness than for drink-driving and alcohol related crime.

Alcoholic Intoxication↗

Dementia and occupational exposure to magnetic fields.

OBJECTIVES: The purpose of the present report was to assess whether occupational magnetic field exposure is a risk factor for dementia, in particular for Alzheimer's disease. METHODS: Case-control analyses were applied to 77 dementia cases, 55 of whom had Alzheimer's disease, ascertained from the population-based Swedish twin register. Two reference groups were derived, with 228 and 238 persons, respectively. Occupations were linked to a job-exposure matrix based on magnetic field measurements. Primary occupation, last occupation before reference date, and the occupation with the highest magnetic field exposure during the subject's lifetime were evaluated. RESULTS: For primary occupation, all relative risk estimates were close to unity. For last occupation, at the exposure level > or = 0.2 microT, a relative risk was found for dementia estimated at 3.3 [95% confidence interval (95% CI) 1.3-8.6] and 3.8 (95% CI 1.4-10.2) for reference groups 1 and 2, respectively. The relative risk for Alzheimer's disease was estimated at 2.4 (95% CI 0.8-6.9) and 2.7 (95% CI 0.9-7.8), respectively. For the occupation with the highest magnetic field exposure, the relative risk estimates were close to unity for reference group 1 and slightly elevated for reference group 2. The relative risk estimates were greater for the subjects who were younger at onset (< or =75 years). CONCLUSIONS: These results only partially support previous findings, but they indicate that occupational magnetic field exposure may possibly influence the development of dementia.

Aged↗

Substantial genetic influence on cognitive abilities in twins 80 or more years old.

General and specific cognitive abilities were studied in intact Swedish same-sex twin pairs 80 or more years old for whom neither twin had major cognitive, sensory, or motor impairment. Resemblance for 110 identical twin pairs significantly exceeded resemblance for 130 fraternal same-sex twin pairs for all abilities. Maximum-likelihood model-fitting estimates of heritability were 62 percent for general cognitive ability, 55 percent for verbal ability, 32 percent for spatial ability, 62 percent for speed of processing, and 52 percent for memory. There was also evidence for the significant influence of idiosyncratic experience as the environmental component that most determines individual differences in cognitive abilities late in life.

Aged↗

Cancer in twins: genetic and nongenetic familial risk factors.

BACKGROUND: Familial clustering has been observed for cancers that occur at specific sites. Most findings, which leave little doubt about the involvement of a heritable (i.e., genetic) component in the development of some cancers, are based on data from "cancer-prone" families or interviews with subjects who have cancer. The study of twins should be of value in cancer epidemiology because twins either are genetically identical or share half of their segregating genes. PURPOSE: We linked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk. METHODS: Same-sex twin pairs with both individuals alive and living in Sweden in 1959-1961 or 1970-1972 were identified in the old cohort (born from 1886 through 1925) or the young cohort (born from 1926 through 1958), respectively, of the Swedish Twin Registry; pairs for whom zygosity (i.e., the number of eggs that gave rise to the twins) could be determined were considered further. The association of cancer with combined genetic and nongenetic familial factors was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer at one of several specific sites with pairs in which neither twin had that cancer. Heritable effects alone were tested by comparing monozygotic (one egg) and dizygotic (two eggs) twin pairs. Statistical methods used in quantitative genetics and standard methods for epidemiologic research were used in parallel to analyze the data. RESULTS AND CONCLUSIONS: In the 10503 twin pairs from the old cohort, 361.7 cases of malignant cancer were identified; 918 malignant cancers were identified in the 12883 twin pairs from the young cohort. When cancer sites with a total number of at least 200 cases and at least one twin pair concordant (i.e., both twins affected) for the site were evaluated, namely, cancers of the stomach, colon and rectum, lung, female breast, and prostate, as well as total cancer, profound genetic and/or nongenetic familial effects were identified in twins from the old cohort. Similar findings were obtained for twins in the young cohort for cancers of the prostate and female breast, as well as for total cancer. Genetic and nongenetic familial effects were also identified in twins from both cohorts for in situ cancer of the cervix. The increase in risk of colon and rectum, breast, cervical, and especially prostate cancer, but not stomach or lung cancer, tended to be greater if a monozygotic rather than a dizygotic twin were affected. IMPLICATIONS: The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general.

Adult↗

Temperance board registration for alcohol abuse in a national sample of Swedish male twins, born 1902 to 1949.

BACKGROUND: Temperance boards were established in Sweden to register and follow up individuals who were seen in legal or medical settings with problems of alcohol abuse. These records, available in a large epidemiologic twin population, have provided an objective and validated measure of alcohol abuse. METHODS: We examined Swedish temperance board registrations from 1929 to 1974 (n = 2516 individual twins) in all male-male Swedish twin pairs of known zygosity from the population-based Swedish Twin Registry; these twin pairs were born from 1902 to 1949 (n = 8935 pairs). RESULTS: The lifetime prevalence and probandwise concordance rates for temperance board registrations were 13.2% and 47.9%, respectively, in monozygotic twins and 14.6% and 32.8%, respectively, in dizygotic twins. Model fitting suggested that genetic and familial-environmental risk factors accounted for 54% (95% confidence interval [CI], 47%-61%) and 14% (95% CI, 8%-19%) of the liability to temperance board registration, respectively; these estimates were stable across birth cohorts. High genetic liability was reflected by large numbers of temperance board registrations and registrations for criminal alcohol use. Elevated familial-environmental liability was indicated by an early age at first registration. CONCLUSIONS: Genetic factors are of major etiologic importance for alcohol abuse in men, while familial environmental factors play a significant but less important role. The etiologic importance of these factors has remained constant in Sweden for men who were born in the first half of the 20th century.

Adult↗

Can personality explain genetic influences on life events?

Previous research in the Swedish Adoption/Twin Study of Aging (SATSA) has found genetic influences on life events (R. Plomin, P. Lichtenstein, N.L. Pedersen, G.E. McClearn, & J.R. Nesselroade, 1990). The present study extends this finding by examining sex differences in genetic and environmental contributions to life events and by examining personality as a mediator of genetic influences on life events in SATSA. Analyses were based on 320 twin pairs, including identical and fraternal twins reared together and apart (mean age = 58.6 years). Controllable, desirable, and undesirable life events were revealed significant genetic variance for women. There was no significant genetic variance for either sex for uncontrollable events. Multivariate analyses of personality (as indexed by Neuroticism, Extraversion, and Openness to Experience) and life events suggest that all of the genetic variance on controllable, desirable, and undesirable life events for women is common to personality. Thus, in this sample of older adult women, genetic influences on life events appear to be entirely mediated by personality.

Adult↗

Heritability for Alzheimer's disease: the study of dementia in Swedish twins.

BACKGROUND: Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease. METHODS: At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models. RESULTS: Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences. CONCLUSIONS: Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.

Age of Onset↗

Moderate genetic influences on plasma levels of plasminogen activator inhibitor-1 and evidence of genetic and environmental influences shared by plasminogen activator inhibitor-1, triglycerides, and body mass index.

Both genes and environmental factors have been reported to influence plasma levels of plasminogen activator inhibitor-1 (PAI-1). However, the relative importance of genetic influences (i.e., heritability) on plasma PAI-1 levels has not yet been investigated. Furthermore, PAI-1 levels are correlated with body mass index (BMI) and triglycerides. These correlations could reflect genetic and/or environmental factors in common to PAI-1, triglycerides, and BMI. We applied multivariate genetic analysis methods to assess the relative importance of genetic and environmental influences on plasma PAI-1 levels and to test the significance of genetic and/or environmental influences shared by PAI-1, triglycerides, and BMI in 217 pairs of middle-aged and elderly twins, of whom 113 pairs were reared apart and 121 pairs were women. The heritability estimate for PAI-1 levels was 42%. Individual-specific environmental factors explained 36% of the variance for PAI-1 levels. The remaining variance of PAI-1 was explained by rearing and residual-familial environmental factors. Furthermore, a genetic correlation of 1.00 between PAI-1 and triglycerides, a rearing environmental correlation of 1.00 between PAI-1 and BMI, a residual-familial environmental correlation of 1.00 between PAI-1 and triglycerides, and a genetic correlation of 0.63 between PAI-1 and BMI, were found. In conclusion, the present results suggest that genetic influences on plasma PAI-1 are moderate. Genetic and shared rearing or residual-familial environmental factors shared by PAI-1, BMI, and triglycerides explain the phenotypic association between these measures. It appears that all the genetic influences for PAI-1 are more or less shared with those for triglycerides and BMI.

Adoption↗

Associations between insulin-like growth factor-I (IGF-I), IGF-binding protein-1, insulin and other metabolic measures after controlling for genetic influences: results from middle-aged and elderly monozygotic twins.

It has previously been shown that the serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic effects to various degrees. From a clinical and preventive point of view, however, it is important to identify potentially modifiable non-genetic factors influencing the levels of these measures. Because monozygotic twin pairs share the same genetic background, differences in phenotypic levels within monozygotic twin paris are believed to be due to non-genetic influences. Accordingly, the associations between intrapair differences in one phenotype and intrapair differences in another phenotype are also due to non-genetic influences. The present sample of 97 pairs of monozygotic twins from the population-based Swedish Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non-genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and insulin after controlling for the genetic influences. IGFBP-1 and glucose were significant predictors for the levels of IGF-I. IGFBP-1 and glucose together explained about one quarter of the non-genetic variation of IGF-I. However, when IGFBP-1 was dropped from the regression model, insulin was the only independent predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF-I. For IGFBP-1, insulin and IGF-I, were the significant non-genetic predictors. Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height, glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5% respectively of the non-genetic variation.

Aged↗

Genetic and environmental architecture of the features of the insulin-resistance syndrome.

The contribution of genetic and environmental effects to the clustering of metabolic factors contained in insulin-resistance syndrome (IRS) is still unclear. To explore the genetic architecture of IRS, we examined a population of elderly twins from the Swedish Adoption/Twin Study of Aging. A sample of 289 pairs of twins (mean age 65.5 years; range 52-86 years), of whom 140 pairs had been reared apart, was studied. The features contained in the IRS consisted of body-mass index (BMI), insulin resistance, triglycerides, HDL cholesterol, and systolic blood pressure. Intraclass correlations, cross-twin correlations, and model-fitting analyses were used to evaluate the relative importance of genetic and environmental influences for variation in and covariation among the components of the syndrome. All of the five principal metabolic components contained in IRS are more or less influenced by a single latent genetic factor, whereas only three of the components (triglycerides, insulin resistance, and HDL cholesterol) are influenced by a latent individual-specific environmental factor. The genetic factor reflected influences of importance to BMI and insulin resistance and to a lesser degree to triglycerides, HDL cholesterol, and systolic blood pressure, whereas the individual-specific environmental factor reflected influences in common to triglycerides and HDL cholesterol and to a lesser degree to insulin resistance. Systolic blood pressure was related to IRS, albeit weakly, only through genetic effects. In conclusion, IRS appears to be influenced by different sets of genetic and environmental mechanisms. The set of genetic influences in common to all the components may initiate the abnormalities underlying IRS.

Aged↗

Models of spouse similarity: applications to fluid ability measured in twins and their spouses.

Genetic influences have consistently been reported to be the principal explanation for resemblance among relatives for intelligence, with shared environmental effects playing a much smaller role. However, crucial to understanding the nature of environmental influences are the mechanisms of assortative mating. Phenotypic assortment, albeit widely assumed or modeled in biometrical analyses, may be less important than other assortment processes, such as social homogamy. Consequently, effects of shared environment may play a greater role than prior studies have suggested. The goal of this study was to resolve environmental and genetic influences on fluid ability based on alternative models of assortment by examining the similarity of monozygotic (MZ) and dizygotic (DZ) twins and their spouses. Raven's Progressive Matrices scores were available from a population-based Swedish sample of 138 twin kinships. The effects of both social homogamy and phenotypic assortment were tested simultaneously in each of two alternate assortment models. A factor/delta path model represented social homogamy as a common factor and phenotypic assortment as a delta path, while a delta/delta path model represented both social homogamy and phenotypic assortment as delta paths. Overall, the factor/delta path model was found to be superior. Results suggested that social homogamy completely explained spouse similarity; phenotypic assortment was not significant. The results of these analyses suggest the presence of shared environmental effects among twins and their spouses, which would have been underestimated if only phenotypic modeled phenotypic assortment may have underestimated the effects of environment.

Adult↗

The treated incidence of psychotic and affective illness in twins compared with population expectation: a study in the Swedish Twin and Psychiatric Registries.

Twin studies of psychiatric illness assume that the genetic and environmental risk factors for psychiatric illness are similar in twins and non-twins and in monozygotic (MZ) and dizygotic (DZ) twins. To test this assumption, we examine whether the treated incidence of psychiatric illness in twins deviates from population expectations or differs between MZ and DZ twins. Using first admissions to the Swedish Psychiatric Registry for the years 1979-83 for all twins born 1886-1958 from the Swedish Twin Registries, we calculated Standardized Morbidity Ratios (SMRs) using national incidence rates together with individually computed person-years at risk in the twin cohort. The diagnoses examined, for which there was more than 393000 person-years of risk, were schizophrenia, other non-affective psychoses (ONAP), bipolar affective illness (BPAI), unipolar affective illness (UPAI) and neurotic depression (ND). The SMRs (and 95% Cls) for all twins were: schizophrenia 0.86 (0.69-1.06), ONAP 1.05 (0.88-1.24), BPAI 1.09 (0.90-1.32), UPAI 1.05 (0.85-1.29) and ND 0.99 (0.88-1.10). This pattern of results did not differ substantially when examined separately by gender or birth cohort. Relative risks for first admissions for MZ v. same-sex DZ twins or same v. opposite-sex DZ twins did not differ significantly from unity for any of the disorders examined. In Sweden, the treated incidence of psychotic and affective disorders in twins does not differ from that found in the general population and does not differ across zygosity groups. These results support the validity of the twin method for the study of psychotic and affective disorders.

Adult↗

Sources of covariation among Mini-Mental State Examination scores, education, and cognitive abilities.

An adoption/twin design was used to address issues concerning the relationship between education and Mini-Mental State Examination (MMSE) performance. Data on general cognitive abilities, education, and MMSE from 110 identical twin pairs and 177 fraternal pairs aged 50 through 88 were analyzed using multivariate quantitative genetic methods. Genetic influences account for 32% and 19% of the variation in MMSE for men and women, respectively. Furthermore, all of the genetic variation in MMSE is in common with genetic variation for cognitive abilities and education. Finally, correlations between education and MMSE (.21 and .16 for men and women, respectively), which were reduced to near zero when cognitive abilities were partialed out, are primarily attributable to genetic effects for cognitive abilities. These results support the hypothesis that the association between education and MMSE performance predominantly reflects genetically mediated cerebral capacity rather than test bias or health-endangering life styles in less educated individuals.

Cognition↗

A co-twin--control study of response to widowhood.

The effects of long-term and recent conjugal bereavement were investigated in a sample of 2,104 Swedish twins followed between 1984 and 1993. In co-twin-control analyses, the bereaved twin experienced significantly more depressive symptoms, more loneliness, and less life satisfaction than the married co-twin. This association existed for recently widowed (< 3 years) of both sexes. Long-term widowed (> 5 years) reported more loneliness than married individuals, and for women there was also a difference in life satisfaction. There were no effects of bereavement on perceived physical health. Individual analyses, which included all respondents regardless of the co-twin's bereavement status, showed the same pattern of results. There was also evidence for an anticipation effect of widowhood indicated by elevated depressive symptoms prior to the spouse's death. Finally, longitudinal analyses showed that it is more stressful to be bereaved when young-old than old-old, but revealed no age differences in adaptation.

Age Factors↗