| 1. |
- Blom, Elin Susanne, et al.
(författare)
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Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
- 2008
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:6, s. 778-83
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multi-point linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon 4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
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| 2. |
- Walum, Hasse, et al.
(författare)
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Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans.
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:37, s. 14153-14156
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Tidskriftsartikel (refereegranskat)abstract
- Pair-bonding has been suggested to be a critical factor in the evolutionary development of the social brain. The brain neuropeptide arginine vasopressin (AVP) exerts an important influence on pair-bonding behavior in voles. There is a strong association between a polymorphic repeat sequence in the 5' flanking region of the gene (avpr1a) encoding one of the AVP receptor subtypes (V1aR), and proneness for monogamous behavior in males of this species. It is not yet known whether similar mechanisms are important also for human pair-bonding. Here, we report an association between one of the human AVPR1A repeat polymorphisms (RS3) and traits reflecting pair-bonding behavior in men, including partner bonding, perceived marital problems, and marital status, and show that the RS3 genotype of the males also affects marital quality as perceived by their spouses. These results suggest an association between a single gene and pair-bonding behavior in humans, and indicate that the well characterized influence of AVP on pair-bonding in voles may be of relevance also for humans.
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| 3. |
- Wirdefeldt, Karin, et al.
(författare)
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Complete ascertainment of Parkinson disease in the Swedish Twin Registry
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 29:12, s. 1765-1773
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Tidskriftsartikel (refereegranskat)abstract
- This report describes the ascertainment of Parkinson disease (PD) in all individuals aged 50 years or older (49,814 individuals) from the Swedish Twin Registry. In phase one of the study, all twins were screened for PD using telephone interviews, with a response rate of 72.7%. In phase two, twins with suspected PD were re-contacted to exclude anyone from follow-up who reported parkinsonian symptoms due to diseases other than PD. In the third phase, in-person clinical evaluations were completed for twins who were still considered PD suspects after phase two and for a sample of co-twins. During the clinical evaluations, we also collected blood samples and information about a variety of environmental exposures. Overall prevalence rate for PD was 496 per 100,000 individuals. Among the 132 PD cases identified, there were only three concordant twin pairs. In total 7.2% of PD cases reported a first degree relative with PD.
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| 4. |
- Yuh, Jongil, et al.
(författare)
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The role of temperament and social support in depressive symptoms: A twin study of mid-aged women
- 2008
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 106:1-2, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although research has found that temperament and social support are associated with depression, these relationships have not been explored in conjunction with one another as they relate to depression using a genetically informative design. This study investigated how the association among the three constructs is mediated. Methods: The sample in this study consisted of 326 pairs of adult monozygotic and dizygotic twins drawn from the Swedish Twin Registry. Twins were mothers of adolescent from married or partnered relationships. The genetic and environmental contributions to the association were evaluated by self-reported measures of temperament, social support, and depressive symptoms. Results: Multivariate genetic model fitting revealed that a moderate portion of genetic influences were common among the three central constructs of harm avoidance, perceived social support, and depressive symptoms. Limitations: The results may not be generalizable to depressive disorders in clinical settings. The measures were self-reported from a cross-sectional study. Conclusions: The findings suggest that the heritable component may contribute to genetic influences on an individual's ability to secure social support and thus to genetic risk for depressive symptomatology in women.
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| 5. |
- Bruder, Carl E G, et al.
(författare)
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Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles
- 2008
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 82:3, s. 763-71
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Tidskriftsartikel (refereegranskat)abstract
- The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
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| 6. |
- 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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| 7. |
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| 8. |
- Svedberg, Pia, et al.
(författare)
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No evidence of sex differences in heritability of irritable bowel syndrome in Swedish twins.
- 2008
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 11:2, s. 197-203
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Tidskriftsartikel (refereegranskat)abstract
- Studies have shown that familial aggregation is of importance for abdominal symptoms including irritable bowel syndrome and there are a few reports of a moderate heritability for irritable bowel syndrome. Sex differences in prevalence and incidence of irritable bowel syndrome have been demonstrated however less is known about sex differences in heritability. The objective was to investigate whether there were sex differences in heritability of irritable bowel syndrome while accounting for different prevalences among women and men in different age groups. A sample of 45,750 Swedish twins, whereof 16,961 were complete twin pairs, participated in a telephone interview. The sample was divided into three age groups (40-54, 55-64 and 65 years and older) and the diagnosis of irritable bowel syndrome was operationally defined with a number of disorder specific symptoms. Standard biometrical model fitting analyses were conducted using raw ordinal data from same-sex and opposite-sex twins. The prevalence of irritable bowel syndrome was greater among women than men and more prevalent at younger ages (e.g., women 10.3%, men 6.3% at ages 40-54 years vs. women 6.1%, men 4% at ages over 65 years). The heritability of the disorder was approximately 25% in all age groups. We found no evidence for sex differences in heritability in any of the age groups, however, models allowing prevalences of irritable bowel syndrome to differ between sexes and age groups fitted best.
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