| 21. |
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| 22. |
- Hong, Mun-Gwan, et al.
(författare)
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Evidence that the gene encoding insulin degrading enzyme influences human lifespan.
- 2008
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:15, s. 2370-8
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Tidskriftsartikel (refereegranskat)abstract
- Studies in model organisms have demonstrated that components of insulin and insulin-like signaling pathways are involved in the regulation of lifespan but the relevance of those findings to humans has remained obscure. Here we provide evidence suggesting that variants of the gene encoding insulin-degrading enzyme (IDE) may be influencing human lifespan. We have employed a variety of models and diverse samples that reproducibly indicate the relative change in IDE genotype frequency across the age spectrum as well as allow the detection of association with age-at-death. A tenable molecular basis of this is suggested by the observation of genetic association with both fasting plasma insulin levels and IDE mRNA expression. Across populations the emergent genetic model is indicative of over-dominance, where heterozygotes of critical markers have increased IDE mRNA expression and insulin levels, and this is reflected in diminished heterozygosity at advanced age. A critical and replicating feature of this study is that change in IDE genotype frequency with advancing age appears to be occurring only in men, and this is supported in that insulin levels are only associated with IDE in men. Results suggest a relationship between a gene that is intimately involved in insulin metabolism and the determination of lifespan in humans, but over-dominance and gender specificity will be important parameters to consider clarifying the biological importance of these findings.
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| 23. |
- Kato, K, et al.
(författare)
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A population-based twin study of functional somatic syndromes
- 2009
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 39:3, s. 497-505
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mechanisms underlying the co-occurrence of the functional somatic syndromes are largely unknown. No empirical study has explicitly examined how genetic and environmental factors influence the co-morbidity of these syndromes. We aimed to examine how the co-morbidity of functional somatic syndromes is influenced by genetic and environmental factors that are in common to the syndromes. METHOD: A total of 31318 twins in the Swedish Twin Registry aged 41-64 years underwent screening interviews via a computer-assisted telephone system from 1998 to 2002. Four functional somatic syndromes (chronic widespread pain, chronic fatigue, irritable bowel syndrome, and recurrent headache) and two psychiatric disorders (major depression and generalized anxiety disorder) were assessed using structured questions based on standard criteria for each illness in a blinded manner. RESULTS: Multivariate twin analyses revealed that a common pathway model with two latent traits that were shared by the six illnesses fit best to the women's data. One of the two latent traits loaded heavily on the psychiatric disorders, whereas the other trait loaded on all four of the functional somatic syndromes, particularly chronic widespread pain, but not on the psychiatric disorders. All illnesses except the psychiatric disorders were also affected by genetic influences that were specific to each. CONCLUSIONS: The co-occurrence of functional somatic syndromes in women can be best explained by affective and sensory components in common to all these syndromes, as well as by unique influences specific to each of them. The findings clearly suggest a complex view of the multifactorial pathogenesis of these illnesses.
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| 24. |
- Kato, Kenji, et al.
(författare)
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Chronic widespread pain and its comorbidities : a population-based study
- 2006
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 166:15, s. 1649-1654
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Tidskriftsartikel (refereegranskat)abstract
- Associations between CWP and most comorbidities are mediated by unmeasured genetic and family environmental factors in the general population. The extent of mediation via familial factors is likely to be disorder specific.
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| 25. |
- Kato, Kenji, et al.
(författare)
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Importance of genetic influences on chronic widespread pain
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:5, s. 1682-1686
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Tidskriftsartikel (refereegranskat)abstract
- Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.
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| 26. |
- Kato, Kenji, et al.
(författare)
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Premorbid predictors of chronic fatigue
- 2006
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Ingår i: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 63:11, s. 1267-1272
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Tidskriftsartikel (refereegranskat)abstract
- Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.
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| 27. |
- Larsson, Mats, et al.
(författare)
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Associations between iris characteristics and personality in adulthood
- 2007
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Ingår i: Biological Psychology. - : Elsevier BV. - 0301-0511 .- 1873-6246. ; 75:2, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Variable and person-oriented analyses were used to explore the associations between personality and three previously untested general iris characteristics: crypts, pigment dots and contraction furrows. Personality data, as measured by the NEO PI-R and ratings of iris characteristics from 428 undergraduate students were collected. Crypts were significantly associated with five approach-related behaviors, i.e., feelings, tendermindedness, warmth, trust and positive emotions, whereas furrows were associated with impulsiveness. These findings suggest that because Pax6 induces tissue deficiencies in both the iris and the left anterior cingulate cortex, Pax6 may influence the extent people engage in approach-related behaviors. The results from using a person-oriented analysis suggested that people with different iris configurations tend to develop along different personality trajectories. Future longitudinal studies, twin-studies and genetic association studies, may benefit from collecting iris data and testing candidate genes for crypts and furrows
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| 28. |
- Michaëlsson, Karl, et al.
(författare)
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Genetic liability to fractures in the elderly
- 2005
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 165:16, s. 1825-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The genetic impact on the causation of osteoporotic fractures is unclear. A large twin study is ideally suited to determine the genetic liability to categories of fracture at various ages. METHODS: A cohort of all 33 432 Swedish twins born from 1896 to 1944 was used to evaluate the genetic liability to fracture occurrence in the elderly. The Swedish Inpatient Registry and computer-assisted telephone interviews enabled us to identify 6021 twins with any fracture, 3599 with an osteoporotic fracture, and 1055 with a hip fracture after the age of 50 years. RESULTS: Genetic variation in liability to fracture differed considerably by type of fracture and age. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation. The age-adjusted heritability of any osteoporotic fracture was slightly greater (0.27; 95% confidence interval [CI], 0.09-0.28), and for hip fracture alone, it was 0.48 (95% CI, 0.28-0.57). Heritability was not attenuated after further adjustment for several known osteoporotic covariates but was considerably greater for first hip fractures before the age of 69 years (0.68; 95% CI, 0.41-0.78) and between 69 and 79 years (0.47; 95% CI, 0.04-0.62) than for hip fractures after 79 years of age (0.03; 95% CI, 0.00-0.26). CONCLUSIONS: The importance of genetic factors in propensity to fractures depends on fracture site and age. The search for susceptibility genes and environmental factors that may modulate expression of these genes in younger elderly patients with hip fracture, the most devastating osteoporotic fracture, should be encouraged. Prevention of fractures in the oldest elderly should focus on lifestyle interventions.
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| 29. |
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| 30. |
- Reynolds, Chandra A, et al.
(författare)
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A survey of ABCA1 sequence variation confirms association with dementia.
- 2009
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 30:9, s. 1348-54
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Tidskriftsartikel (refereegranskat)abstract
- We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23-1.57, p=7.7x10(-8)). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of beta-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease.
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