The genetic liability to disability retirement: a 30-year follow-up study of 24,000 Finnish twins

Background

No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders.

Methods

The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement.

Results

The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71).

Conclusions

A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation.     

Complex phenotypic profiles leading to ozone sensitivity in Arabidopsis thaliana mutants

Genetically tractable model plants offer the possibility of defining the plant O₃ response at the molecular level. To this end, we have isolated a collection of ozone (O₃)-sensitive mutants of Arabidopsis thaliana . Mutant phenotypes and genetics were characterized. Additionally, parameters associated with O₃ sensitivity were analysed, including stomatal conductance, sensitivity to and accumulation of reactive oxygen species, antioxidants, stress gene-expression and the accumulation of stress hormones. Each mutant has a unique phenotypic profile, with O₃ sensitivity caused by a unique set of alterations in these systems. O₃ sensitivity in these mutants is not caused by gross deficiencies in the antioxidant pathways tested here. The rcd3 mutant exhibits misregulated stomata. All mutants exhibited changes in stress hormones consistent with the known hormonal roles in defence and cell death regulation. One mutant, dubbed re-8 , is an allele of the classic leaf development mutant reticulata and exhibits phenotypes dependent on light conditions. This study shows that O₃ sensitivity can be determined by deficiencies in multiple interacting plant systems and provides genetic evidence linking these systems.     

Bmx Tyrosine Kinase Has a Redundant Function Downstream of Angiopoietin and Vascular Endothelial Growth Factor Receptors in Arterial Endothelium

The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this study, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta-galactosidase substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.     

Two new variants of the lipocalin allergen Bos d 2

Allergens from various sources have been shown to comprise several isoforms. In the present study, a series of chromatographic steps was carried out to separate the lipocalin allergen Bos d 2 isoforms present in cow dander. Subsequent HPLC-MS–MS analyses revealed two new Bos d 2 variants. In one of the proteins, tyrosine (Y83) was substituted by aspartic acid, and in the other protein valine (V102) was replaced by alanine. We propose the three Bos d 2 variants be named as Bos d 2.0101 (previously sequenced Bos d 2), Bos d 2.0102 and Bos d 2.0103. Our results suggest that molecular polymorphism is a common property among lipocalin allergens. Since allergen isoforms may show variation in their IgE binding and/or T-cell reactivity, all of the many allergen forms should be taken into account when planning preparations for immunotherapy.     

Predictors of Weight Change in Middle‐aged and Old Men

Objective: Studies on weight change and mortality have yielded inconclusive results. This 10‐year prospective study was undertaken to improve understanding of factors affecting weight change. Research Methods and Procedures: The subjects were 1143 men, aged 36 to 88 years (mean, 53.3 years) at entry. A questionnaire was filled in at entry and at the end of the follow‐up with queries on weight, height, weight at the age of 20, physician‐diagnosed diseases, smoking, alcohol use, dietary habits, leisure physical activity, occupation, present occupational activity, living conditions (living alone or cohabiting), and former athletic status. Further information on morbidity was obtained from selected national registers. Factors predicting weight change during the study were identified by stepwise linear multiple regression analysis. Results: The mean 10‐year weight change was 0.8 (range, ?29 to +24) kg. Age at entry (β‐coefficient, ?0.17, SE 0.02), weight at entry (β, ?0.03, SE 0.01), diabetes at entry (β, ?3.55, SE 1.02), diabetes diagnosed after entry (β, ?3.94, SE 0.96), malignant cancer (β, ?1.60, SE 0.70), being a smoker (β, ?1.59, SE 0.48), and increased physical activity (β, ?1.27, SE 0.54) were significantly (p < 0.05) associated with weight loss in the final model. The model explained 13% of the variance of weight change. Discussion: The results emphasize the complexity of weight change. Some factors associated with weight change are apparently negatively, and some positively, associated with health. This could explain the equivocal findings on weight change and mortality in the literature.     

Low doses of ultraviolet radiation and oxidative damage induce dramatic accumulation of mitochondrial DNA replication intermediates,fork regression,and replication initiation shift

Mitochondrial DNA is prone to damage by various intrinsic as well as environmental stressors. DNA damage can in turn cause problems for replication, resulting in replication stalling and double-strand breaks, which are suspected to be the leading cause of pathological mtDNA rearrangements. In this study, we exposed cells to subtle levels of oxidative stress or UV radiation and followed their effects on mtDNA maintenance. Although the damage did not influence mtDNA copy number, we detected a massive accumulation of RNA:DNA hybrid–containing replication intermediates, followed by an increase in cruciform DNA molecules, as well as in bidirectional replication initiation outside of the main replication origin, O_H. Our results suggest that mitochondria maintain two different types of replication as an adaptation to different cellular environments; the RNA:DNA hybrid–involving replication mode maintains mtDNA integrity in tissues with low oxidative stress, and the potentially more error tolerant conventional strand-coupled replication operates when stress is high.     

Time-dependent influence of some sedating agents on basic haematological values in various artio- and perissodactylids

Basic haematological values in 32 animals of five species were estimated after administration of sedating agents. In all species under investigation, a time-dependent decrease of erythrocyte counts, haematocrit values and haemoglobin content was noted during the first 30 min after sedation, for the following 30 min the lowered values remained essentially without any change in zebras. Derived parameters, mean corpuscular haemoglobin, mean corpuscular Hb concentration and mean corpuscular volume did not change during the period of observation. Only insignificant changes in leukocyte count and in the proportion of lymphocytes and neutrophiles were registered. The shortest possible time between sedation and blood sampling is recommended to minimalize a distortion especially in the red blood picture.     

Reactive oxygen species signaling and stomatal movement in plant responses to drought stress and pathogen attack

Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO_2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors, including water status, light, CO_2 levels and pathogen attack, as well as endogenous signals, such as abscisic acid and apoplastic reactive oxygen species(ROS). Under abiotic and bioticstress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network,primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO_2 signaling, and immunity responses.Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli.     

Lysinuric Protein Intolerance (LPI) Gene Maps to the Long Arm of Chromosome 14

Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids and by hyperammonemia. Linkage analysis in 20 Finnish LPI families assigned the LPI gene locus to the proximal long arm of chromosome 14. Recombinations placed the locus between framework markers D14S72 and MYH7, a 10-cM interval in which the markers D14S742, D14S50, D14S283, and TCRA showed no recombinations with the phenotype. The phenotype was in highly significant linkage disequilibrium with markers D14S50, D14S283, and TCRA. The strongest allelic association obtained with marker TCRA, resulting in a P(excess) value of .98, suggests that the LPI gene locus lies in close proximity to this marker, probably within a distance of < 100 kb.