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- Rietschel, Liz, et al.
(författare)
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Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes.
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
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| 2. |
- Partonen, Timo, et al.
(författare)
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Three circadian clock genes Per2, Arnt1, and Npas2 contribute to winter depression
- 2007
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Ingår i: Annals of Medicine. - New York : Informa Healthcare. - 0785-3890 .- 1365-2060. ; 39:3, s. 229-238
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Tidskriftsartikel (refereegranskat)abstract
- Background. Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression.Methods. In silico analysis of the biological effects of allelic differences suggested the target single-nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk.Results. SAD was associated with variations in each of the three genes in gene-wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination.Conclusion. Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.
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