| 1. |
- Mueller, Stefanie H., et al.
(författare)
-
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
-
Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
|
|
| 2. |
- Hori, Yasunori, et al.
(författare)
-
The Discovery and Follow-up of Four Transiting Short-period Sub-Neptunes Orbiting M Dwarfs
- 2024
-
Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 167:6
-
Tidskriftsartikel (refereegranskat)abstract
- Sub-Neptunes with radii of 2-3 R ⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of R p = 2.740 − 0.079 + 0.082 R ⊕ , 2.769 − 0.068 + 0.073 R ⊕ , 2.120 ± 0.067 R ⊕, and 2.830 − 0.066 + 0.068 R ⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M ⊕, <19.5 M ⊕, <6.8 M ⊕, and <15.6 M ⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass-radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called “radius valley,” are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2-0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.
|
|
| 3. |
- Graham-Bermann, Sandra A., et al.
(författare)
-
Adults’ Explanations for Intimate Partner Violence During Childhood and Associated Effects
- 2017
-
Ingår i: Journal of Clinical Psychology. - : John Wiley & Sons. - 0021-9762 .- 1097-4679. ; 73:6, s. 652-668
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Exposure to intimate partner violence (IPV) is known to challenge children’s optimal development. This study sought to associate participants’ beliefs about IPV held during childhood with their adjustment as adults, and to compare their beliefs from childhood to their beliefs in early adulthood.Method: A nationally representative sample of 703 Swedish young adults reported on their past and present beliefs about the causes of their parents’ IPV. Standardized measures assessed their mental health (anxiety, depression, and traumatic stress symptoms) and the quality of their relationships as adults.Results: The most common explanations for IPV were that the perpetrator suffered from physical or mental illness, had relationship problems, or was distressed. Participants were less likely to blame themselves for IPV or to believe that the perpetrator was cruel when they were adults, compared to their reports of themselves as children. Women were more likely to attribute mental or physical illness as the cause of the perpetrator’s IPV. Childhood beliefs that the perpetrator was debilitated (from mental illness or substance abuse) and cruel (took pleasure in violence and/or despised the child) were associated with greater mental health problems and poorer relationship quality in adulthood.Conclusion: Evaluation of children’s harmful beliefs about IPV could be useful in adapting intervention services aimed at ameliorating negative personal causal attributions.
|
|
| 4. |
- Howell, Kathryn H., et al.
(författare)
-
The relationship between types of childhood victimisation and young adulthood criminality
- 2017
-
Ingår i: CBMH. Criminal behaviour and mental health. - : Wiley-Blackwell. - 0957-9664 .- 1471-2857. ; 27:4, s. 341-353
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research suggests that some types of childhood abuse and neglect are related to an increased likelihood of perpetrating criminal behaviour in adulthood. Little research, however, has examined associations between multiple different types of childhood victimisation and adult criminal behaviour.Aims: We sought to examine the contribution of multiple and diverse childhood victimisations on adult criminal behaviour. Our central hypothesis was that, after controlling for gender, substance use and psychopathy, each type of childhood victimisation - specifically experience of property offences, physical violence, verbal abuse, sexual abuse, neglect and witnessed violence - would be positively and independently related to criminal behaviour in young adults.Methods: We examined data from a large, nationally representative sample of 2244 young Swedish adults who reported at least one form of victimisation, using hierarchical regression analysis to also account for gender, substance use and psychopathy.Results: Experiences of physical assaults, neglect and witnessing violence as a child were significantly associated with adult criminal behaviour, but not experiences of property, verbal or sexual victimizations.Conclusions: Our findings help to identify those forms of harm to children that are most likely to be associated with later criminality. Even after accounting for gender, substance misuse and psychopathology, childhood experience of violence - directly or as a witness - carries risk for adulthood criminal behaviour, so such children need targeted support and treatment.
|
|
| 5. |
- Kapoor, Pooja Middha, et al.
(författare)
-
Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
|
|
| 6. |
- Miller, Laura E., et al.
(författare)
-
Perpetration patterns and environmental contexts of IPV in Sweden : relationships with adult mental health
- 2014
-
Ingår i: International Journal of Child Abuse & Neglect. - : Elsevier BV. - 0145-2134 .- 1873-7757. ; 38:1, s. 147-158
-
Tidskriftsartikel (refereegranskat)abstract
- Although excellent data exist on the overall prevalence of childhood exposure to intimatepartner violence (IPV), there is less information available on the specific patterns of IPVexposure in childhood and how they influence adult mental health. The current study exa-mines 703 Swedish adults who reported exposure to IPV in childhood. Participants werepart of a large national study on violence exposure. They provided an extensive history of their exposure to IPV and maltreatment experiences during childhood via electronically administered questionnaires. Mean comparison and multivariate regression methods were employed to assess differences in violence severity by reported perpetration pattern(mother-only, father-only, bidirectional or other), the association between violence severity and environmental context, and the contribution of these characteristics to adult mental health outcomes. Overall, violence perpetrated in public and by fathers was more severe and was related to poorer mental health outcomes in adulthood for child witnesses. These findings provide important insight into possible clinical "flags" for identifying children at high risk for exposure to IPV and abuse in the home.
|
|
| 7. |
- Wang, Xiaoliang, et al.
(författare)
-
Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
- 2022
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 x 10(-8) as genome-wide significant, and p-values < 1 x 10(-5) as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 10(-8)) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.
|
|
