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- Bendre, M, 1983-, et al.
(författare)
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INTERACTION OF MAOA GENOTYPE, DNA METHYLATION AND STRESSFUL LIFE EVENTS IN RELATION TO ALCOHOL MISUSE
- 2016
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Konferensbidrag (refereegranskat)abstract
- Epigenetic mechanisms are candidate mediators of the effects of stressful life events (SLEs) on the brain. Stress, especially during critical developmental periods, might render an individual vulnerable to alcohol misuse later in life. Previous studies report sex-dependent interactions of Monoamine Oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) and SLEs in association with alcohol misuse, however whether DNA methylation moderates this effect is unknown. The aim of the present longitudinal study was to investigate whether the interaction between MAOA-uVNTR genotype, promoter DNA methylation and SLEs associates with alcohol misuse in 56 males and 78 females whom as adolescents had sought treatment for substance misuse in Sweden. The functional MAOA-uVNTR polymorphism, consisting of a 30-bp repeated sequence present in 2, 3, 3.5, 4, or 5 copies, was genotyped. Alleles with less or more than 3 copies were grouped into short (S) and long (L) alleles, respectively. Methylation analysis of 16 candidate CpGs within the MAOA promoter (Chr.X: 43515544 - 43515991) was performed. Data on SLEs (i.e. physical abuse by parents, sexual abuse and experience of victimization by peers) was obtained from a self-report questionnaire. Alcohol misuse at the time of first contact with the clinic and after five years was assessed using the Alcohol Use Disorder Identification Test (AUDIT). The general linear model with type III sum of square was used to analyze interaction effects. In males but not females, an interaction effect between MAOA-uVNTR genotype, DNA methylation and sexual or physical abuse was observed on follow-up AUDIT scores. Sexually or physically abused males carrying the S allele and lower DNA methylation reported higher AUDIT scores whereas the opposite effect was observed in non-sexually or non-physically abused males. On the other hand, irrespective of exposure to sexual or physical abuse, L allele male carriers with lower DNA methylation displayed lower AUDIT scores. No interaction between MAOA-uVNTR genotype, DNA methylation and victimization by peers was found in either sex. These preliminary results suggest that DNA methylation might moderate the association between alcohol misuse and the interaction of MAOA-uVNTR genotype and abuse in males.
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- Kallak, Theodora Kunovac, 1985-, et al.
(författare)
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Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain
- 2017
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 177:4, s. 379-388
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Prenatal androgen exposure has been suggested to play a role in polycystic ovary syndrome. Given the limited information on what maternal characteristics influence maternal testosterone levels, and the even less explored routes by which female fetus androgen exposure would occur, the aim of this study was to investigate the impact of maternal age, BMI, weight gain, depressed mood and aromatase SNPs on testosterone levels in maternal serum and amniotic fluid of female fetuses.METHODS: Blood samples from pregnant women (n = 216) obtained in gestational weeks 35-39, and pre-labor amniotic fluid samples from female fetuses (n = 56), taken at planned Caesarean section or in conjunction with amniotomy for induction of labor, were analyzed. Maternal serum testosterone and amniotic fluid testosterone and cortisol were measured by tandem mass spectrometry.RESULTS: Multiparity (β = -0.28, P < 0.001), self-rated depression (β = 0.26, P < 0.001) and weight gain (β = 0.18, P < 0.05) were independent explanatory factors for the maternal total testosterone levels. Maternal age (β = -0.34, P < 0.001), weight gain (β = 0.19, P < 0.05) and amniotic fluid cortisol levels (β = 0.44, P < 0.001) were independent explanatory factors of amniotic fluid testosterone in female fetuses, explaining 64.3% of the variability in amniotic fluid testosterone.WIDER IMPLICATIONS OF THE FINDINGS: Young maternal age and excessive maternal weight gain may increase the prenatal androgen exposure of female fetuses. Further studies are needed to explore this finding.
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- Ning, Yilin, et al.
(författare)
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Handling ties in continuous outcomes for confounder adjustment with rank-ordered logit and its application to ordinal outcomes
- 2020
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Ingår i: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 29:2, s. 437-454
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Tidskriftsartikel (refereegranskat)abstract
- The rank-ordered logit (rologit) model was recently introduced as a robust approach for analysing continuous outcomes, with the linear exposure effect estimated by scaling the rank-based log-odds estimate. Here we extend the application of the rologit model to continuous outcomes with ties and ordinal outcomes treated as imperfectly-observed continuous outcomes. By identifying the functional relationship between survival times and continuous outcomes, we explicitly establish the equivalence between the rologit and Cox models to justify the use of the Breslow, Efron and perturbation methods in the analysis of continuous outcomes with ties. Using simulation, we found all three methods perform well with few ties. Although an increasing extent of ties increased the bias of the log-odds and linear effect estimates and resulted in reduced power, which was somewhat worse when the model was mis-specified, the perturbation method maintained a type I error around 5%, while the Efron method became conservative with heavy ties but outperformed Breslow. In general, the perturbation method had the highest power, followed by the Efron and then the Breslow method. We applied our approach to three real-life datasets, demonstrating a seamless analytical workflow that uses stratification for confounder adjustment in studies of continuous and ordinal outcomes.
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- Vachon-Presseau, Etienne, et al.
(författare)
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Corticolimbic anatomical characteristics predetermine risk for chronic pain
- 2016
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 139, s. 1958-1970
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex-amygdala-accumbens, ventral medial prefrontal cortex-amygdala, and orbitofrontal cortex-amygdala-hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex-amygdala-accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors.
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