| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Bryois, J., et al.
(author)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 4. |
- Eijsbouts, C., et al.
(author)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 5. |
- Wightman, D. P., et al.
(author)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 8. |
- Dunham, I, et al.
(author)
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The DNA sequence of human chromosome 22
- 1999
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
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Journal article (peer-reviewed)
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| 11. |
- Brennan, Seán J., 1995-, et al.
(author)
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Spectroscopic observations of progenitor activity 100 days before a Type Ibn supernova
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Journal article (peer-reviewed)abstract
- Obtaining spectroscopic observations of the progenitors of core-collapse supernovae is often unfeasible, due to an inherent lack of knowledge as to what stars experience supernovae and when they will explode. In this Letter we present photometric and spectroscopic observations of the progenitor activity of SN 2023fyq before the He-rich progenitor explodes as a Type Ibn supernova. The progenitor of SN 2023fyq shows an exponential rise in flux prior to core collapse. Complex He I emission line features are observed in the progenitor spectra, with a P Cygni-like profile, as well as an evolving broad base with velocities of the order of 10 000 km s−1. The luminosity and evolution of SN 2023fyq is consistent with a Type Ibn, reaching a peak r-band magnitude of −18.8 mag, although there is some uncertainty regarding the distance to the host, NGC 4388, which is located in the Virgo cluster. We present additional evidence of asymmetric He-rich material being present both prior to and after the explosion of SN 2023fyq, which suggests that this material survived the ejecta interaction. Broad [O I], C I, and the Ca II triplet lines are observed at late phases, confirming that SN 2023fyq was a genuine supernova, rather than a non-terminal interacting transient. SN 2023fyq provides insight into the final moments of a massive star’s life, demonstrating that the progenitor is likely highly unstable before core collapse.
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| 12. |
- Chen, Z. H., et al.
(author)
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The Hydrogen-poor Superluminous Supernovae from the Zwicky Transient Facility Phase I Survey. I. Light Curves and Measurements
- 2023
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 943:1
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Journal article (peer-reviewed)abstract
- During the Zwicky Transient Facility (ZTF) Phase I operations, 78 hydrogen-poor superluminous supernovae (SLSNe-I) were discovered in less than 3 yr, constituting the largest sample from a single survey. This paper (Paper I) presents the data, including the optical/UV light curves and classification spectra, while Paper II in this series will focus on the detailed analysis of the light curves and modeling. Our photometry is primarily taken by ZTF in the g, r, and i bands, and with additional data from other ground-based facilities and Swift. The events of our sample cover a redshift range of z = 0.06 − 0.67, with a median and 1σ error (16% and 84% percentiles) of zmed=0.265. The peak luminosity covers −22.8 mag ≤ Mg,peak ≤ −19.8 mag, with a median value of -21.48. The light curves evolve slowly with a mean rest-frame rise time of trise = 41.9 ± 17.8 days. The luminosity and timescale distributions suggest that low-luminosity SLSNe-I with a peak luminosity ∼−20 mag or extremely fast-rising events (<10 days) exist, but are rare. We confirm previous findings that slowly rising SLSNe-I also tend to fade slowly. The rest-frame color and temperature evolution show large scatters, suggesting that the SLSN-I population may have diverse spectral energy distributions. The peak rest-frame color shows a moderate correlation with the peak absolute magnitude, i.e., brighter SLSNe-I tend to have bluer colors. With optical and UV photometry, we construct the bolometric luminosity and derive a bolometric correction relation that is generally applicable for converting g, r-band photometry to the bolometric luminosity for SLSNe-I.
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| 18. |
- Zhang, G., et al.
(author)
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Genetic Associations with Gestational Duration and Spontaneous Preterm Birth
- 2017
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In: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1156-1167
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Journal article (peer-reviewed)abstract
- BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (< 37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P< 5.0x10(-8)) or an association with suggestive significance (P< 1.0x10(-6)) in the discovery set. In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.
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| 19. |
- Becker, Joel, et al.
(author)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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In: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Journal article (peer-reviewed)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 20. |
- Chen, Z. H., et al.
(author)
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The Hydrogen-poor Superluminous Supernovae from the Zwicky Transient Facility Phase I Survey. II. Light-curve Modeling and Characterization of Undulations
- 2023
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 943:1, s. 42-
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Journal article (peer-reviewed)abstract
- We present analysis of the light curves (LCs) of 77 hydrogen-poor superluminous supernovae (SLSNe I) discovered during the Zwicky Transient Facility Phase I operation. We find that the majority (67%) of the sample can be fit equally well by both magnetar and ejecta-circumstellar medium (CSM) interaction plus 56Ni decay models. This implies that LCs alone cannot unambiguously constrain the physical power sources for an SLSN I. However, 23% of the sample show inverted V-shape, steep-declining LCs or features of long rise and fast post-peak decay, which are better described by the CSM+Ni model. The remaining 10% of the sample favors the magnetar model. Moreover, our analysis shows that the LC undulations are quite common, with a fraction of 18%-44% in our gold sample. Among those strongly undulating events, about 62% of them are found to be CSM-favored, implying that the undulations tend to occur in the CSM-favored events. Undulations show a wide range in energy and duration, with median values (and 1σ errors) being as 1.7 % − 0.7 % + 1.5 % E rad , total and 28.8 − 9.1 + 14.4 days, respectively. Our analysis of the undulation timescales suggests that intrinsic temporal variations of the central engine can explain half of the undulating events, while CSM interaction (CSI) can account for the majority of the sample. Finally, all of the well-observed He-rich SLSNe Ib either have strongly undulating LCs or the LCs are much better fit by the CSM+Ni model. These observations imply that their progenitor stars have not had enough time to lose all of the He-envelopes before supernova explosions, and H-poor CSM are likely to present in these events.
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| 21. |
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| 22. |
- Frazier-Wood, Alexis C., et al.
(author)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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In: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Journal article (peer-reviewed)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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