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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Bauer, M., et al.
(författare)
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Solar insolation in springtime influences age of onset of bipolar I disorder
- 2017
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:6, s. 571-582
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Forskningsöversikt (refereegranskat)abstract
- Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.
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| 7. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 8. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 9. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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- Ryu, Y. -H., et al.
(författare)
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OGLE-2016-BLG-1190Lb : The First Spitzer Bulge Planet Lies Near the Planet/Brown-dwarf Boundary
- 2018
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 155:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of OGLE-2016-BLG-1190Lb, which is likely to be the first Spitzer microlensing planet in the Galactic bulge/ bar, an assignation that can be confirmed by two epochs of high-resolution imaging of the combined source-lens baseline object. The planet's mass, M-p = 13.4 +/- 0.9 M-J, places it right at the deuteriumburning limit, i. e., the conventional boundary between planets and brown dwarfs. Its existence raises the question of whether such objects are really planets (formed within the disks of their hosts) or failed stars (lowmass objects formed by gas fragmentation). This question may ultimately be addressed by comparing disk and bulge/bar planets, which is a goal of the Spitzer microlens program. The host is a G dwarf, M-host = 0.89. +/- 0.07 M-circle dot, and the planet has a semimajor axis a similar to 2.0 au. We use Kepler K2 Campaign 9 microlensing data to break the lens-mass degeneracy that generically impacts parallax solutions from Earth-Spitzer observations alone, which is the first successful application of this approach. The microlensing data, derived primarily from near-continuous, ultradense survey observations from OGLE, MOA, and three KMTNet telescopes, contain more orbital information than for any previous microlensing planet, but not quite enough to accurately specify the full orbit. However, these data do permit the first rigorous test of microlensing orbital-motion measurements, which are typically derived from data taken over < 1% of an orbital period.
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