| 1. |
- de Jong, S, et al.
(författare)
-
Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
-
Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Arnau-Soler, A, et al.
(författare)
-
Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
-
Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Conley, Daniel, et al.
(författare)
-
Long-term changes and impacts of hypoxia in Danish coastal waters
- 2007
-
Ingår i: Ecological Applications. - : Wiley. - 1051-0761. ; 17:5, s. 165-184
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A 38-year record of bottom water dissolved oxygen concentrations in coastal marine ecosystems around Denmark (1965-2003) and a longer partially reconstructed record of total nitrogen (TN) inputs (1900-2003) were assembled to describe long-term patterns in hypoxia and anoxia. Interannual variations in bottom water oxygen concentrations were analyzed in relation to various explanatory variables (bottom temperature, wind speed, advective transport, TN loading). Reconstructed TN loads peaked in the 1980s with a gradual decline to the present, commensurate with a legislated nutrient reduction strategy. Mean bottom water oxygen concentrations during summer have significantly declined in coastal marine ecosystems, decreasing substantially during the 1980s and were extremely variable thereafter. Despite decreasing TN loads, the worst hypoxic event ever recorded in open waters occurred in 2002. For estuaries and coastal areas, bottom water oxygen concentrations were best described by TN input from land and wind speed in July-September, explaining 52% of the interannual variation in concentrations. For open sea areas, bottom water oxygen concentrations were also modulated by TN input from land, however, additional significant variables included advective transport of water and Skagerrak surface water temperature and explained 49% of interannual variations in concentrations. Reductions in benthic species number and alpha diversity were significantly related to the duration of the 2002 hypoxic event. Gradual decreases in diversity measures (species number and alpha diversity) over the first 2-4 weeks show that the benthic community undergoes significant changes before the duration of hypoxia is severe enough to cause the community to collapse. Enhanced sediment-water fluxes of NH4+ and PO43- occur with hypoxia, increasing nutrient concentrations in the water column, and stimulating additional phytoplankton production. Repeated hypoxic events have changed the character of benthic communities and how organic matter is processed in sediments. Our data suggest that repeated hypoxic events lead to an increase in susceptibility of Danish waters to eutrophication and further hypoxia.
|
|
| 18. |
- Czamara, D, et al.
(författare)
-
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
