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Nancy L Pedersen

Publications and source records attributed to Nancy L Pedersen.

At least 55 records · Page 3Linked to original sources

Chronic fatigue in a population sample: definitions and heterogeneity.

BACKGROUND: Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation. METHOD: We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42-64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis. RESULTS: Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness. CONCLUSIONS: Our data are consistent with the 'existence' of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition - impairing chronic fatigue not due to a known cause - would represent a way forward.

Adult↗

Twin analyses of chronic fatigue in a Swedish national sample.

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits. METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness. RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects. CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

Adult↗

Age at onset and familial risk for major depression in a Swedish national twin sample.

BACKGROUND: In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD). METHOD: Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models. RESULTS: Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to approximately 35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD. CONCLUSION: In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.

Age of Onset↗

Quantitative genetic analysis of latent growth curve models of cognitive abilities in adulthood.

Though many cognitive abilities exhibit marked decline over the adult years, individual differences in rates of change have been observed. In the current study, biometrical latent growth models were used to examine sources of variability for ability level (intercept) and change (linear and quadratic effects) for verbal, fluid, memory, and perceptual speed abilities in the Swedish Adoption/Twin Study of Aging. Genetic influences were more important for ability level at age 65 and quadratic change than for linear slope at age 65. Expected variance components indicated decreasing genetic and increasing nonshared environmental variation over age. Exceptions included one verbal and two memory measures that showed increasing genetic and nonshared environmental variance. The present findings provide support for theories of the increasing influence of the environment with age on cognitive abilities.

Adoption↗

Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions.

Lipid levels in plasma strongly influence the risk for coronary heart disease. To localise and subsequently identify genes affecting lipid levels, we performed four genome-wide linkage scans followed by combined linkage/association analysis. Genome-scans were performed in 701 dizygotic twin pairs from four samples with data on plasma levels of HDL- and LDL-cholesterol and their major protein constituents, apolipoprotein AI (ApoAI) and Apolipoprotein B (ApoB). To maximise power, the genome scans were analysed simultaneously using a well-established meta-analysis method that was newly applied to linkage analysis. Overall LOD scores were estimated using the means of the sample-specific quantitative trait locus (QTL) effects inversely weighted by the standard errors obtained using an inverse regression method. Possible heterogeneity was accounted for with a random effects model. Suggestive linkage for HDL-C was observed on 8p23.1 and 12q21.2 and for ApoAI on 1q21.3. For LDL-C and ApoB, linkage regions frequently coincided (2p24.1, 2q32.1, 19p13.2 and 19q13.31). Six of the putative QTLs replicated previous findings. After fine mapping, three maximum LOD scores mapped within 1 cM of major candidate genes, namely APOB (LOD=2.1), LDLR (LOD=1.9) and APOE (LOD=1.7). APOB haplotypes explained 27% of the QTL effect observed for LDL-C on 2p24.1 and reduced the LOD-score by 0.82. Accounting for the effect of the LDLR and APOE haplotypes did not change the LOD score close to the LDLR gene but abolished the linkage signal at the APOE gene. In conclusion, application of a new meta-analysis approach maximised the power to detect QTLs for lipid levels and improved the precision of their location estimate.

Adolescent↗

Mania in the Swedish Twin Registry: criterion validity and prevalence.

BACKGROUND: In population surveys, the assessment of mania is commonly done by trained lay interviewers using structured diagnostic instruments: the validity of this approach has been questioned. We examined the criterion validity and prevalence of lifetime mania in a survey of Swedish twins conducted with interview methodology usually applied in psychiatric epidemiology. METHODS: 41 838 individuals in the Swedish Twin Registry were evaluated via a telephone interview that included the eight DSM-IV mania items, and these data were merged with inpatient hospitalization discharge diagnoses from two comprehensive national registries (the criterion). An algorithm with eight cut-points was used to diagnose lifetime mania, and compared by a receiver operator characteristic curve to the criterion. The algorithm requiring at least four positive items resembling a DSM-IV diagnosis. RESULTS: History of hospitalization for a psychiatric condition that included a manic episode was present for 0.7% of all living twins, and predicted non-response to the survey (OR = 0.5; 95% CI = 0.4-0.6). The incidence rate for first hospitalization was 2.1/10 000 year(-1). For > or =1 symptom (first cut-point), the prevalence, sensitivity and specificity were 3.6%, 39.0% and 96.6%; for > or = 4 symptoms (DSM-IV-like cut-point) 2.6%, 36.5% and 97.6%; and for eight symptoms 0.3%, 18.0% and 99.8%. Positive predictive values were, respectively, 5.5%, 7.0% and 29.8%. CONCLUSIONS: The performance of the telephone screening for mania by lay interviewers in terms of positive predictive power was not satisfactory; despite a high specificity, the false positive rate was high. The low population prevalence of mania, non-response bias, criterion choice and inherent limitations of the interviewing method are among the explanations. Assessment of a lifetime manic episode based on lay interviewer screening may yield misleading data.

Bipolar Disorder↗

Complexity of work and risk of Alzheimer's disease: a population-based study of Swedish twins.

We examined the association between risk of dementia or Alzheimer's disease (AD) and occupation by using measures of complexity of work with data, people, and things. The study included 10,079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. We diagnosed dementia by means of a two-stage procedure--cognitive impairment screening followed by full clinical evaluation. We analyzed data with case-control and cotwin control designs. The cotwin control design provides control over genetic and familial factors. In the case-control study, controlling for age, gender, and level of education, we found that more complex work with people was associated with reduced risk of AD. Greater complexity of work with people and data was protective in twin pairs discordant for AD. Findings suggest that greater complexity of work, and particularly complex work with people, may reduce the risk of AD.

Aged↗

Self-rated health in a longitudinal perspective: a 9-year follow-up twin study.

OBJECTIVES: This study first considers age and cohort explanations for age-related changes in mean values and variance in self-rated health. Second, it evaluates the contributions of genes and environments to self-rated health measured longitudinally. METHODS: Subjects were participants in the Swedish Adoption/Twin Study of Aging. Self-rated health assessments were collected in four waves over a 9-year follow-up period, from one or both members of 788 twin pairs. Linear mixed effect models were used to test for differences in means and variances. Structural equation modeling provided estimates of genetic and environmental components of variance and contributions to stability. RESULTS: Changes in means and variance within cohorts seem to reflect illness. Earlier-born cohorts are more variable and have lower self-rated health. These cohort differences were not explained by childhood socioeconomic status. Correlations between time points reflect both environmental and genetic factors. DISCUSSION: Both genes and environments contribute to self-rated health longitudinally, and both age and cohort effects are seen. Age-related changes in self-rated health can be attributed to illness. Cohort differences are most likely attributable to socially mediated and individual-specific environmental factors.

Adoption↗

Heritability of SF-36 among middle-age, middle-class, male-male twins.

OBJECTIVE: We sought to examine the relative importance of genetic and environmental factors for the MOS SF-36; a widely used, valid, and reliable measure of health-related quality of life and to discuss incorporating genetic influences into health services research. DATA SOURCES: Data are from a nationally distributed, nonclinical cohort of 2928 middle age, middle-class, male-male twin members of the Vietnam Era Twin Registry. STUDY DESIGN: This was a secondary data analysis, classic twin heritability analysis. DATA COLLECTION: A telephone survey was used to collect information on alcohol-related problems and health services use, including the SF-36. PRINCIPAL FINDINGS: Variance component analyses indicated that additive genetic factors accounted for 17% to 33% of the variance for each of the 8 domains of the SF-36. Shared environment accounted for 0% to 12% of the variance for each domain, with the majority of variance for each domain accounted for by nonshared, or unique environment and error. Physical and mental health summary measures indicated that approximately one-third of the variance was accounted for by additive genetic factors and the remainder accounted for by nonshared environment and error. Clinical condition, history of alcohol dependence, had a small-but-significant influence for all domains. Including condition proved to be a better-fitting model. However, confidence intervals temper uniform statistical significance for genetic factors. CONCLUSIONS: This study assessed the heritability of the SF-36 in a nonclinical, community sample of middle age, middle-class all-male twins. The moderate genetic effects on SF-36 domain and summary measures are new findings and thus may affect interpretations of SF-36 as a measure of health-related quality of life. Ideally, trait-based measures should identify genetic sources of variation and thus help understand any bias of the true effects of SF-36. Still the majority of variance is accounted for by nonshared or unique environmental factors and error. By extension, increased understanding of the importance of genetic and environmental factors that influence either predictors or outcomes of interest will expand the level of scientific debate in health services research and improve predictability.

Adult↗

Performance on neurocognitive tests by co-twins to dementia cases compared to normal control twins.

Nondemented co-twins of twins who were diagnosed as demented were compared to randomly selected members of normal control twin pairs in which both members of the pair were nondemented. Nondemented co-twins included 23 monozygotic and 62 dizygotic twins; there were 27 normal control twins. Both monozygotic and dizygotic nondemented co-twins of dementia cases scored significantly lower than normal control twins on 5 of 10 cognitive tests. Moreover, monozygotic co-twins of dementia cases had a generally lower score profile than dizygotic co-twins of dementia cases did. These findings show that being at greater genetic risk for dementia is reflected in cognitive performance even in the absence of a diagnosis of dementia.

Aged↗

Comparative rating measures of health and environmental exposures: how well do twins agree?

Twins are sometimes used as proxy informants but little is known about reliability and validity of the information thus obtained. The present study asks: (1) to what extent do twin pairs agree with each other on comparative ratings of health, psychosocial traits, and environmental exposures?; and (2) how well do comparative ratings agree with usual self-reported information about the exposures? Using 55 monozygotic (MZ) and 71 dizygotic (DZ) same-sex pairs reared together, percentage agreement was calculated for 44 comparative ratings. Pairs agreed on average about half of the time. Agreement was higher for more discrete exposures, such as smoking, but lower for more subjective variables, such as the degree to which life is experienced as stressful. Signed rank tests were used to contrast comparative ratings to differences in self-reports. Differences between twin partners in their self-report indices, where available, were in the direction suggested by the comparative rating. Comparative ratings appear most accurate for smoking and alcohol use, and less consistent for mental health symptoms and self-rated health.

Adult↗

Genetic correlations among texture characteristics in the human iris.

PURPOSE: To estimate the magnitude of genetic correlations among five general textural characteristics of the human iris. METHODS: Color photographs of iris were available from 100 monozygotic and 99 dizygotic twin pairs. Comparative scales were constructed based on ratings of the subjects' left iris. To explore the genetic and environmental covariation among frequency of Fuchs' crypts, frequency of pigment dots, iris color, the extension, and distinction of Wolfflin nodules, and contraction furrows, a structural equation model with Cholesky decomposition was applied to variance-covariance matrices for monozygotic (MZ) and dizygotic (DZ) pairs. RESULTS: Significant genetic correlations fell between -0.22 and 0.44 and accounted almost entirely for the phenotypic correlations among the iris characteristics. No evidence for individual specific environmental effects in common to the characteristics was found. CONCLUSIONS: The modest genetic correlations indicate that there is little overlap in the genetic influence for these characteristics. Candidate genes with embryological and histological expression patterns in the eye could potentially influence the iris characteristics' variability.

Adolescent↗

Accounting for depressive symptoms in women: a twin study of associations with interpersonal relationships.

BACKGROUND: This study examined how interpersonal relationships, specifically marital quality and adequacy of social support, are associated with depressive symptoms among women. METHODS: A sample of 326 female monozygotic and dizygotic twin pairs and their spouses was drawn from the Swedish Twin Registry. Associations among the three variables were evaluated by comparing similarities among monozygotic and dizygotic female twin pairs. RESULTS: Interpersonal relationships contributed between 18% and 31% of the variance for depressive symptoms in women. Associations among the three variables were accounted for by genetic influences when women's reports were used. Non-shared environmental influences were important for the association between marital quality and depressive symptoms when a combination of husband and wife reports of marital quality were used. LIMITATIONS: The data is cross-sectional and the generalizability of these findings to depressive symptoms in men or to individuals with major depression is not clear. CONCLUSIONS: These findings indicate important associations among marital quality, social support and depressive symptoms in women, which should be taken into consideration for prevention and intervention strategies targeting depression.

Adult↗

A cladistic model of ACE sequence variation with implications for myocardial infarction, Alzheimer disease and obesity.

Sequence variation in ACE, which encodes angiotensin I converting enzyme, contributes to a large proportion of variability in plasma ACE levels, but the extent to which this impacts upon human disease is unresolved. Most efforts to associate ACE with other heritable traits have involved a single Alu insertion/deletion polymorphism, despite the probable existence of other functional sequence variants with effects that may not be consistently detectable by solely typing the Alu indel. Here, utilizing single nucleotide polymorphisms (SNPs) that differentiate major ACE clades in European populations, we demonstrate a number of significant phenotype associations across more than 4000 Swedish individuals. In a systematic analysis of metabolic phenotypes, effects were detected upon several traits, including fasting plasma glucose levels, insulin levels and measures of obesity (P-values ranging from 0.046 to 8.4 x 10(-6)). Extending cladistic models to the study of myocardial infarction and Alzheimer disease, significant associations were observed with greater effect sizes than those typically obtained in large-scale meta-analyses based on the Alu indel. Population frequencies of ACE genotypes were also found to change with age, congruent with previous data suggesting effects upon longevity. Clade models consistently outperformed those based upon single markers, reinforcing the importance of taking into consideration the possible confounding effects of allelic heterogeneity in this genomic region. Utilizing computational tools, potential functional variants are highlighted that may underlie phenotypic variability, which is discussed along with the broader implications these results may have for studies attempting to link variation in ACE to human disease.

Alzheimer Disease↗

Sensitivity and specificity of dementia coding in two Swedish disease registries.

The authors investigated the sensitivity and specificity of dementia identification in two Swedish disease registries by using clinical diagnoses from two population-based studies as gold standards. The probability of dementia detected by the Inpatient Discharge Registry was 55% for prevalent patients and 31% for incident patients and was higher than detection by the Cause of Death Registry. Specificity was 98% for the Inpatient Discharge Registry and 100% for the Cause of Death Registry.

Aged↗

No evidence for heritability of Parkinson disease in Swedish twins.

BACKGROUND: Although several genes are implicated in Parkinson disease (PD), they explain only a small fraction of cases. The etiology of most cases is yet unknown. OBJECTIVE: To evaluate heritability of PD in same-sexed and opposite-sexed twin pairs in the Swedish Twin Registry (STR). METHODS: All twins in the STR born in 1950 or earlier and alive in 1998 (n = 50,150) were included. The authors screened 33,780 twins in 14,082 pairs for PD by telephone interviews and linked the STR to the Swedish Inpatient Discharge Register. Two hundred forty-seven twins with self-reported PD or a PD diagnosis in the Inpatient Discharge Register (called "possible PD") and 517 twins who reported parkinsonian symptoms or use of antiparkinsonian medication ("suspected parkinsonism or movement disorder") were identified. RESULTS: For possible PD, there were only two concordant pairs, both female dizygotic. Similarly, concordances were low in all zygosity groups when the definition of affected was expanded to include twins with suspected parkinsonism or movement disorder in addition to possible PD. Sex differences in the relative importance of genetic and environmental effects were indicated with a marginally larger familial component in women. The best-fitting structural equation model included only environmental components of variance. CONCLUSIONS: These results suggest that environmental factors are most important in the etiology of PD. Compared with other complex diseases, the importance of genetic effects in PD is notably low. The preponderance of discordant twin pairs provides an ideal material for studying environmental risk factors and potential genotype-by-environment interaction.

Age of Onset↗

Comorbid type 2 diabetes mellitus and hypertension exacerbates cognitive decline: evidence from a longitudinal study.

BACKGROUND: diabetes and hypertension are two highly prevalent diseases in the old population. They are highly related such that comorbidity is common. OBJECTIVES: to examine (i) the independent impact of the respective diseases on cognitive decline in very old age and (ii) the interactive impact of the two diseases on cognitive decline. SUBJECTS: 258 individuals (mean age = 83 years), all non-demented at baseline. Of these, 128 individuals (non-cases) were free from diabetes and hypertension, 92 individuals had a diagnosis of hypertension, 16 had a type 2 diabetes mellitus diagnosis without hypertension, and 22 had comorbid diabetes and hypertension. METHOD: a population-based longitudinal study of ageing (The OCTO-Twin Study), including four measurement occasions 2 years apart. The Mini-Mental State Examination was used to measure general cognitive function. Data were analysed using SAS Proc Mixed multilevel modelling. RESULTS: longitudinal trajectories indicated a steeper decline in cognitive function related to diabetes but not related to hypertension. However, the results indicated greatest cognitive decline among persons with comorbid diabetes and hypertension. CONCLUSIONS: it is concluded that comorbidity of diabetes and hypertension produce a pronounced cognitive decline. This finding emphasises the importance of prevention and treatment of those highly prevalent diseases in the old population.

Aged↗

Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease.

We recently reported that a linkage disequilibrium (LD) block on chromosome 10q encompassing the gene encoding insulin-degrading enzyme ( IDE) harbors sequence variants that associate with Alzheimer disease (AD). Evidence also indicated effects upon a number of quantitative indices of AD severity, including age-at-onset (AAO). Since linkage of this immediate region to AAO has been shown in both AD and Parkinson disease (PD), we have explored the possibility that polymorphism within this LD block might also influence PD. Utilizing single nucleotide polymorphisms that delineate common haplotypes from this region, we observed significant evidence of association with AAO in an Australian PD case-control sample. Analyses were complemented with AAO data from two independent Swedish AD case samples, for which previously reported findings were replicated. Results were consistent between AD and PD, suggesting the presence of equivalent detrimental and protective alleles. These data highlight a genomic region in the proximity of IDE that may contribute to AD and PD in a similar manner.

Age of Onset↗