| 21. |
|
|
| 22. |
- Mullins, Niamh, et al.
(författare)
-
GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
- 2019
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
|
|
| 23. |
- Bigdeli, TB, et al.
(författare)
-
Genetic effects influencing risk for major depressive disorder in China and Europe
- 2017
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:3, s. e1074-
-
Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Block, K, et al.
(författare)
-
Characterization of a minichromosome derived from the transposing element TE1 in Drosophila melanogaster
- 1991
-
Ingår i: Hereditas. - : Wiley-Blackwell Publishing, Inc.. - 0018-0661. ; , s. 82-83
-
Konferensbidrag (refereegranskat)abstract
- The transposing element TEI contains the structural genes white and roughest from the Drosophilr X-chromosome. These genes are flanked by FB-elements, which are responsible for the mobility. At one occasion the TE, probably together with an adjacent segment in chromosome 2. has formed a minichromosome. This chromosome contains both the structural genes, the FB-elements,some centromeric and/or telomeric heterochromatin. It probably has a centromere as well, as it is transferred to the offspring at a high rate. From this minichromosome a smaller one has originated, probably through the loss of the region from chromosome 2 and some heterochromatin. This smaller minichromosome has been characterized in the following way: 1. Size determination hy pulsed field gel electrophoresis. -The chromosome turned out to be little more than one megabase. 2. y-irradiation of DNA from the minichromosome. ~ The aim of this experiment is to find out if the chromosome is circular or linear. A radiation dose which causes one break within a circle ought to accumulate DNA of the same size as the minichromosome. In this case no accumulation occurred and thus the chromosome is probably linear. 3. Cloning of sequences from the minichromosome. ~ A low melting agarose gel was run and a fragment was cut out from a region which contained DNA fragments of the same size as the minichromosome. The DNA was cut simultaneously by EcoR I and Pst I and ligated into the vector pBS containing T7 and T3 primers. The ligated DNA was amplified by the PCR method, which rendered several fragments of varying size. These fragments were ligated into the vector pCR1000TM. Positive clones are being analysed at present. With these clones we intend to construct a map of the minichromosome.
|
|
