| 1. |
- Bryois, J., et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)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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| 2. |
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| 3. |
- Eijsbouts, C., et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Wightman, D. P., et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Ganna, A., et al.
(författare)
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Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6456
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Tidskriftsartikel (refereegranskat)abstract
- Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.
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| 8. |
- Harpold, A. A., et al.
(författare)
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Laser vision : lidar as a transformative tool to advance critical zone science
- 2015
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2881-2897
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Tidskriftsartikel (refereegranskat)abstract
- Observation and quantification of the Earth's surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of critical zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and biosphere shape and maintain the 'zone of life', which extends from the top of unweathered bedrock to the top of the vegetation canopy. Fundamental to CZ science is the development of transdisciplinary theories and tools that transcend disciplines and inform other's work, capture new levels of complexity, and create new intellectual outcomes and spaces. Researchers are just beginning to use lidar data sets to answer synergistic, transdisciplinary questions in CZ science, such as how CZ processes co-evolve over long timescales and interact over shorter timescales to create thresholds, shifts in states and fluxes of water, energy, and carbon. The objective of this review is to elucidate the transformative potential of lidar for CZ science to simultaneously allow for quantification of topographic, vegetative, and hydrological processes. A review of 147 peer-reviewed lidar studies highlights a lack of lidar applications for CZ studies as 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % had an interdisciplinary focus. A handful of exemplar transdisciplinary studies demonstrate lidar data sets that are well-integrated with other observations can lead to fundamental advances in CZ science, such as identification of feedbacks between hydrological and ecological processes over hillslope scales and the synergistic co-evolution of landscape-scale CZ structure due to interactions amongst carbon, energy, and water cycles. We propose that using lidar to its full potential will require numerous advances, including new and more powerful open-source processing tools, exploiting new lidar acquisition technologies, and improved integration with physically based models and complementary in situ and remote-sensing observations. We provide a 5-year vision that advocates for the expanded use of lidar data sets and highlights subsequent potential to advance the state of CZ science.
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| 9. |
- Becker, Joel, et al.
(författare)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Tidskriftsartikel (refereegranskat)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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