| 1. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Garshick, Eric, et al.
(författare)
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Respiratory Health after Military Service in Southwest Asia and Afghanistan An Official American Thoracic Society Workshop Report
- 2019
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Ingår i: Proceedings of the American Thoracic Society online. - : American Thoracic Society. - 1546-3222 .- 1943-5665. ; 16:8, s. E1-E16
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Tidskriftsartikel (refereegranskat)abstract
- Since 2001, more than 2.7 million U.S. military personnel have been deployed in support of operations in Southwest Asia and Afghanistan. Land-based personnel experienced elevated exposures to particulate matter and other inhalational exposures from multiple sources, including desert dust, burn pit combustion, and other industrial, mobile, or military sources. A workshop conducted at the 2018 American Thoracic Society International Conference had the goals of: 1) identifying key studies assessing postdeployment respiratory health, 2) describing emerging research, and 3) highlighting knowledge gaps. The workshop reviewed epidemiologic studies that demonstrated more frequent encounters for respiratory symptoms postdeployment compared with nondeployers and for airway disease, predominantly asthma, as well as case series describing postdeployment dyspnea, asthma, and a range of other respiratory tract findings. On the basis of particulate matter effects in other populations, it also is possible that deployers experienced reductions in pulmonary function as a result of such exposure. The workshop also gave particular attention to constrictive bronchiolitis, which has been reported in lung biopsies of selected deployers. Workshop participants had heterogeneous views regarding the definition and frequency of constrictive bronchiolitis and other small airway pathologic findings in deployed populations. The workshop concluded that the relationship of airway disease, including constrictive bronchiolitis, to exposures experienced during deployment remains to be better defined. Future clinical and epidemiologic research efforts should address better characterization of deployment exposures; carry out longitudinal assessment of potentially related adverse health conditions, including lung function and other physiologic changes; and use rigorous histologic, exposure, and clinical characterization of patients with respiratory tract abnormalities.
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| 3. |
- Moritz, Steffen, et al.
(författare)
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Beyond words : Sensory properties of depressive thoughts
- 2014
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Ingår i: Cognition & Emotion. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0269-9931 .- 1464-0600. ; 28:6, s. 1047-1056
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Tidskriftsartikel (refereegranskat)abstract
- Verbal thoughts (such as negative cognitions) and sensory phenomena (such as visual mental imagery) are usually conceptualised as distinct mental experiences. The present study examined to what extent depressive thoughts are accompanied by sensory experiences and how this is associated with symptom severity, insight of illness and quality of life. A large sample of mildly to moderately depressed patients (N = 356) was recruited from multiple sources and asked about sensory properties of their depressive thoughts in an online study. Diagnostic status and symptom severity were established over a telephone interview with trained raters. Sensory properties of negative thoughts were reported by 56.5% of the sample (i.e., sensation in at least one sensory modality). The highest prevalence was seen for bodily (39.6%) followed by auditory (30.6%) and visual (27.2%) sensations. Patients reporting sensory properties of thoughts showed more severe psychopathological symptoms than those who did not. The degree of perceptuality was marginally associated with quality of life. The findings support the notion that depressive thoughts are not only verbal but commonly accompanied by sensory experiences. The perceptuality of depressive thoughts and the resulting sense of authenticity may contribute to the emotional impact and pervasiveness of such thoughts, making them difficult to dismiss for their holder.
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| 4. |
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| 5. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 6. |
- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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