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| 2. |
- Saarentaus, EC, et al.
(author)
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Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
- 2023
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 83-
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Journal article (peer-reviewed)abstract
- Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
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| 3. |
- Saarentaus, EC, et al.
(author)
-
Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 83-
-
Journal article (peer-reviewed)abstract
- Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
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| 4. |
- Hautakangas, H, et al.
(author)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
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Journal article (peer-reviewed)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 5. |
- Paskova, Tanja, 1961-, et al.
(author)
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Characterization of mass-transport grown GaN by hydride vapour-phase epitaxy
- 2004
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In: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248 .- 1873-5002. ; 273:1-2, s. 118-128
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Journal article (peer-reviewed)abstract
- A comprehensive study of the morphological, optical and microstructural properties of mass-transport (MT) and conventionally grown GaN by hydride vapour-phase epitaxy is presented. Spatially resolved techniques have been utilized to reveal in a comparative way, the characteristics of the material grown either in predominant vertical or lateral growth modes. A strong donor-acceptor pair (DAP) emission is observed from the MT regions with a distinctive intensity contrast between the exciton and DAP emission bands from MT and nontransport regions. Secondary ion mass spectroscopy and imaging were employed to investigate the impurity incorporation into different regions. An increase of residual oxygen and aluminium impurity concentrations was found in the MT areas. In addition, positron annihilation spectroscopy showed a strong signal of Ga vacancy clusters in the MT grown material. The increase of the point defect concentrations of both Ga vacancy and oxygen impurity, most likely forming defect complexes, is related to the enhancement of the DAP emission.
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| 6. |
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| 7. |
- Paskova, Tanja, et al.
(author)
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Donor-acceptor pair emission enhancement in mass-transport-grown GaN
- 2005
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 98:3, s. 033508-
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Journal article (peer-reviewed)abstract
- A dominating donor-acceptor pair (DAP) emission at about 3.27 eV is observed in the photoluminescence and cathodoluminescence spectra of intentionally undoped mass-transport (MT)-grown GaN, while only a weak presence of the DAP emission is recorded in the as-grown hydride vapor phase epitaxial GaN. A comparative study of impurity and native defect incorporation in the as-grown and MT GaN was performed, showing a significant increase of oxygen and empty clusters involving Ga vacancy and oxygen in the MT GaN. Based on the observed results as well as on doping analysis of the structure and kinetic analysis of the emission intensities, we propose an acceptorlike complex, creating a state as a semiclassical potential well near the valence-band top due to the local tensile strain caused by the empty clusters to be responsible for the dominating behavior of the DAP emission. © 2005 American Institute of Physics.
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| 8. |
- Raemoe, JT, et al.
(author)
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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
- 2023
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 157-
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Journal article (peer-reviewed)abstract
- Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p < 5 × 10−8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
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| 9. |
- Rämö, JT, et al.
(author)
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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
- 2023
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 157-
-
Journal article (peer-reviewed)abstract
- Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p < 5 × 10−8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
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| 10. |
- Tuomisto, F, et al.
(author)
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Dissociation of V-Ga-O-N complexes in HVPE GaN by high pressure and high temperature annealing
- 2006
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In: Physica status solidi. B, Basic research. - : Wiley. - 0370-1972 .- 1521-3951. ; 243:7, s. 1436-1440
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Journal article (peer-reviewed)abstract
- We have used positron annihilation spectroscopy to study the high-pressure annealing induced thermal recovery of vacancy defects in free-standing GaN grown by hydride vapor phase epitaxy (HYPE). The results show that the in-grown Ga vacancy complexes recover after annealing at 1500-1700 K. Comparison of the experimental positron data with ab-initio calculations indicates that the Doppler broadening measurement of the electron momentum distribution is sensitive enough to distinguish between the N and O atoms surrounding the Ga vacancy. We show that the difference between the isolated V-Ga in electron irradiated GaN and the V-Ga-O-N complexes in highly O-doped GaN is clear, and the Ga vacancy related defect complexes that start dissociating at 1500 K can be identified as V-Ga-O-N pairs.
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