Biomedical subjects

N L Pedersen

Publications and source records attributed to N L Pedersen.

At least 19 recordsLinked to original sources

PubMed2003

Association between depressed mood in the elderly and a 5-HTR2A gene variant.

The aim of this study was to investigate any possible association between depressed mood in the elderly and two candidate SNPs in the serotonin system: one in the 5-HTR2A gene promotor (-1438 G/A) and one in the 5-HT transporter gene (-925 C/A). DNA from a population-based Swedish twin sample (N = 1,592; mean age = 73) was genotyped using Pryosequencing trade mark. An association was found between the 5-HTR2A gene promotor polymorphism and depressed mood (OR: 1.5, CI: 1.1-2.1) for the A/A genotype in the total sample. When the sample was analyzed by gender, a significant association (OR: 2.4, CI: 1.4-4.4) was found for males and the A/A genotype, but not for females. The 5-HT transporter gene was not associated with depressed mood in this elderly population. These results suggest that there might be different genetic mechanisms for males and females contributing to the development of depressed mood in the elderly.

Aged↗

PubMed2003

Stressful life events and affective illness.

OBJECTIVE: To investigate the association between the occurrence of affective illnesses and the number/type of experienced negative stressful life events in a twin material. A case-control study with an unrelated twin as control to the case and a co-twin control study were both undertaken with the same material. METHOD: Postal questionnaire responses were used for confirming diagnosis and to inventory stressful life events. Risk ratios (RR) for groups of events were calculated using conditional logistic regression. RESULTS: A dose-response relationship was observed for the association between stressful life events and affective illness. The RRs for specific groups of exposures were higher in the co-twin control study and higher for dizygotic twin pairs than for monozygotic twin pairs. CONCLUSION: Individuals with a history of affective illness select themselves into high-risk environments, in part due to their genetic propensity to the disease. Thus, the association represents a classic genotype-environment correlation.

Case-Control Studies↗

PubMed2003

A note on cluster headache in a population-based twin register.

Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.

Adult↗

PubMed2002

Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study.

BACKGROUND: Little is known about the role of genetic and environmental factors in irritable bowel syndrome. Various extra-intestinal manifestations are more prevalent in cases than in controls. Genetic effects may be important in the liability to develop functional bowel disorders. AIMS: To evaluate the associations of irritable bowel syndrome with several disorders co-morbid with the condition, using both a case-control design and a co-twin control design. METHODS: A sample of 850 Swedish twin pairs, aged 18-85 years, was contacted for a telephone interview. Through a diagnostic algorithm, 72 unrelated cases of irritable bowel syndrome and 216 age- and gender-matched controls were identified. Fifty-eight twin pairs discordant for irritable bowel syndrome were evaluated in co-twin analyses. RESULTS: Renal problems (odds ratio (OR)=3.3; confidence interval (CI), 1.3-8.2), obesity (OR=2.6; CI, 1.0-6.4), underweight in the past (OR=2.4; CI, 1.1-6.4), gluten intolerance (OR=9.0; CI, 1.4-60.1), rheumatoid arthritis (OR=3.2; CI, 1.1-9.4) and poor self-rated health (OR=1.8; CI, 1.0-3.2) were significantly associated with irritable bowel syndrome. In the co-twin analyses, the only factors maintaining significance were renal and recurrent urinary tract problems. CONCLUSIONS: The association between irritable bowel syndrome and renal and urinary tract problems does not reflect a genetic or familial mediation. Eating disorders in childhood represent a familial-environmental influence on irritable bowel syndrome, whereas the association with rheumatoid arthritis and perhaps gluten intolerance probably reflects genetic mediation.

Adult↗

PubMed2002

Heritability of death from coronary heart disease: a 36-year follow-up of 20 966 Swedish twins.

OBJECTIVE: The aim of the present study was to evaluate and distinguish between environmental and genetic effects for death from coronary heart disease (CHD) as well as to determine whether the importance of genetic influences is changing with age. DESIGN: A cohort study with a follow-up time of 36 years. SUBJECTS: The cohort drawn for the present study includes 20 966 twins born in Sweden between 1886 and 1925 where both twins within a pair still lived within the country in 1961. METHODS: Concordances and correlated gamma-frailty model were used to assess and distinguish between genetic and environmental influences as well as to evaluate age-related changes in genetic influences. RESULTS: A total number of 4007 CHD-deaths (2208 males, and 1799 females) was observed. The probability of dying from CHD given that one's twin partner already has died from CHD decreased with increasing age, particularly amongst males. The genetic variation in susceptibility to death from CHD was moderately large, and decreased slightly across time, particularly amongst males. The heritability was 0.57 (95% CI, 0.45-0.69) amongst male twins, and 0.38 (0.26-0.50) amongst female twins. CONCLUSIONS: The genetic contribution to the variation in CHD-mortality was moderate both in females and males. Furthermore, although genetic effects appeared to be greater at younger ages of death, our findings clearly suggest that genetic factors are in operation throughout the entire life span.

Adult↗

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

Multiple-threshold models for genetic influences on age of onset for Alzheimer disease: findings in Swedish twins.

Twin studies of dementia have typically used relatively simple 2 x 2 contingency tables with one threshold to estimate the relative importance of genetic variance for liability to disease. These designs are inadequate for addressing issues of age at onset, censoring of data, and distinguishing shared environmental effects from age effects. Meyer and Breitner [1998: Am J Med Genet 81:92-97] applied a multiple-threshold model to the NAS-NRC Twin Panel (average age of onset, 63.5 years) and report that additive genetic effects and shared environmental effects account for 37% and 35% of the variation, respectively, in age of onset for Alzheimer disease. We apply a modified version of their model to the Study of Dementia in Swedish Twins (average age of onset, 75 years) and find that genetic effects account for 57%-78% of the variance, whereas shared environmental effects are of no importance. Heritability is lower when thresholds are freely estimated rather than fixed to the population prevalences. We interpret the findings to suggest that models with free thresholds confound influences on longevity with influences for the disease. Multiple-threshold models, however, do not confound age effects with shared environmental influences.

Age of Onset↗

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

Genetics of affective disorders.

Despite substantial evidence for heritability in affective disorders the contributing genes have proven elusive. Here we discuss the genetic epidemiology of depression, as well as methodological issues and results from molecular genetic studies. There has been rapid advances in genetics, genomics and statistical modelling, facilitating the search for molecular mechanisms underlying affective disorders and several strategies reviewed in this paper hold promise to provide progress in the field. Considering the poorly understood biological basis of vulnerability to affective disorders, the identification of genes involved in the pathophysiology will unravel mechanisms and pathways that could permit more personalized therapeutic strategies and result in new targets for pharmacological intervention.

Animals↗

PubMed2001

Health locus of control in late life: a study of genetic and environmental influences in twins aged 80 years and older.

The factor structure of health locus of control (Form A; K. A. Wallston, B. S. Wallston, & R. DeVellis, 1978) was examined in 420 octogenarians (M age = 83.2 years), and the contributions of genetic and environmental factors to health-control beliefs in 141 octogenarian twin pairs (71 identical, 70 same-sex fraternal) were estimated. Factor analyses reproduced previously proposed factors (Internal, Chance, and Powerful Others). Associations between health-control beliefs and life satisfaction, depression, and other health-related measures (e.g., self-rated health, outpatient contacts, and hospitalization), were modest. Quantitative genetic analyses revealed significant shared environmental influence on the Chance subscale, and significant familiality (attributable to a combination of genetic and shared environmental influences) on the Powerful Others subscale; there was no evidence of familiality on the Internal subscale.

Aged↗

PubMed2001

A longitudinal analysis of anxiety and depressive symptoms.

The authors modeled depressive and anxiety symptom data from 1,391 participants in a longitudinal study of middle-aged and older Swedish twins (M age = 60.9 years, SD = 13.3). Although anxiety and depression were highly correlated, a model with distinct Anxiety and Depression factors fit the data better than models with Positive and Negative Affect factors or a single Mental Health factor. Lack of well-being was associated with anxiety rather than depression. Over two 3-year intervals, anxiety symptoms led to depressive symptoms, but the relationship was not reciprocal. Anxiety symptoms were more stable than depression. These findings provide additional support for the idea that anxiety symptoms may reflect a personality trait such as neuroticism more than do depressive symptoms and suggest that low positive affect may not be as specific to depression among older adults as in younger people.

Adult↗

PubMed2001

The effect of the beta(2) adrenoceptor gene Thr164Ile polymorphism on human adipose tissue lipolytic function.

A rare beta(2)-adrenoceptor gene polymorphism, Thr164Ile, has been described that impairs receptor function when transfected into cell lines. We investigated whether the polymorphism influences native receptor function by studying lipolysis in freshly isolated subcutaneous fat cells from 236 apparently healthy subjects. Twelve subjects were heterozygous for the 164Ile variant. The fat cells of Ile carriers displayed a 6 fold increase (P=0.02) in the lipolytic EC(50) of terbutaline (a selective beta(2)-adrenoceptor agonist), but no change in the lipolytic action of dobutamine (a selective beta(1)-adrenoceptor agonist), compared with the Thr carriers. Maximum adrenoceptor agonist stimulated lipolysis did not differ between Thr and Ile carriers. The influence of two other polymorphisms (Arg16Gly and Gln27Glu) in the beta(2)-adrenoceptor gene was considered. Six 164Ile carriers also carried the 16Gly and 27Glu alleles. The latter combination occurred among 105 of the 164Thr carriers. For the 16Gly27Glu subgroup, the EC(50) of terbutaline was about 10 fold higher in 164Ile as than in 164Thr carriers (P=0.02) but there was no difference between genotypes in maximum terbutaline action. There was no difference between groups in dobutamine action. In conclusion, the 164Ile variant of the beta(2)-adrenoceptor is associated with a decreased native adipocyte receptor function, as evidenced by a marked increase in the half maximal effective concentration of the lipolytic action of a selective beta(2)-adrenoceptor agonist. This suggests that genetic variance in the beta(2)-adrenoceptor gene might be important for catecholamine function in humans, at least as far as adipocyte lipolysis is concerned.

Adipose Tissue↗

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↗

PubMed2001

Olfactory functioning and cognitive abilities: a twin study.

A Swedish version of the National Geographic Smell Survey (Wysocki and Gilbert 1989) was completed by 227 twin pairs from the Swedish Adoption/Twin Study of Aging. Twins ranged in age from 45 to 89 years. Quantitative genetic analysis of four measures of olfactory functioning indicated moderate heritability for odor identification and perceived intensity and nonsignificant heritability for odor detection and perceived pleasantness. Bivariate analyses revealed that the relationship between odor identification and measures of verbal ability was primarily genetically mediated. The results provided further support for the hypothesis that odor identification and verbal ability in general tap the same cognitive domain (Larsson 1997).

Aged↗

PubMed2001

Education and the risk of Alzheimer's disease: findings from the study of dementia in Swedish twins.

The association between dementia and education was studied in 143 twin pairs discordant for dementia, using a matched-pair design, and in 221 dementia cases and 442 unrelated controls from the same twin registry, using a case-control design. Low education was defined as 6 years or less of schooling. Case-control analyses with prevalent cases showed low education to be a risk for Alzheimer's disease but not dementia in general. Low education did not significantly predict incident cases. In the matched-pairs analysis, which controls for genetic and other familial influences, differences in education between demented twins and twin partners were not statistically significant. However, for Alzheimer's disease, odds ratios resulting from matched pairs and case-control analyses were similar. Twins' comparative reports about intellectual involvement earlier in their lives suggest a long-standing difference on this dimension, with less involvement by the twin who became demented.

Aged↗

PubMed2001

Deficits in controlled processing may predict dementia: a twin study.

This study tested for differential patterns of cognitive decline in 33 twin pairs for which both were nondemented, but 1 member of the pair went on to develop dementia. Compared with their nondemented twin partners, twins who later developed dementia already showed poorer performance on tests of memory and attention, visuospatial-reasoning skills, and perceptual speed and the Mini-Mental State Examination (MMSE). The authors suggest that this cluster of tests reflects deficits in controlled rather than automatic cognitive processes. Nondemented twin partners of the twins who became demented were also compared with 33 matched controls selected from pairs in which both members remained nondemented. Nondemented twin partners scored lower than matched controls on tests of verbal ability, memory and attention, and perceptual speed and the MMSE. This finding indicates that nondemented twin partners of demented twins are at elevated risk themselves for becoming demented, and further suggests that certain areas of cognition are compromised prior to diagnosis of dementia.

Aged↗

PubMed2001

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↗

PubMed2001

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↗