| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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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.
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| 3. |
- Hedrick, Philip W., et al.
(författare)
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Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves
- 2017
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Ingår i: Journal of Heredity. - : OXFORD UNIV PRESS INC. - 0022-1503 .- 1465-7333. ; 108:2, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding.
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| 4. |
- Laikre, Linda, 1960-, et al.
(författare)
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Planned cull endangers Swedish wolf population
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 377:6602
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Tidskriftsartikel (refereegranskat)abstract
- In May, the Swedish Parliament announced a goal to reduce the Swedish wolf population from about 400 to about 200 individuals (1). This action further threatens this highly endangered population, which is genetically isolated and inbred. Scientific advice for improvements has not been implemented (2, 3).The Swedish Parliament proposed this drastic cull at a time when biodiversity is a global focus. The 50-year anniversary of the first UN conference on the environment was celebrated in June, and the UN Convention on Biological Diversity (CBD) will soon finalize its global biodiversity framework for 2020 to 2050. Sweden’s actions are inconsistent with the country’s obligations under the CBD and European Union law.Few wild populations are as well studied as the Scandinavian wolf. Genetic monitoring has provided a full pedigree since the population was reestablished in the 1980s after extinction, and the data confirm persisting genetic isolation (4–6). Hunting, conducted both legally and illegally, has prevented population expansion and the influx of genetic variation.Three founders comprised the population’s genetic origin until 2007, and only three more wolves have subsequently contributed genetically to the present population (6). The genetic base is thus extremely narrow, and genomic erosion has been confirmed (7, 8). The average level of inbreeding is similar to the level found in the offspring of two full siblings (6). Inbreeding in this population has been shown to reduce litter size (4). Also, high frequencies of anatomical defects (9) and male reproductive disorders (10) have been observed.To make this population viable, population size and immigration must increase. So far, the population has been too small, and limited immigration followed by inbreeding could lead to extinction, similar to the Isle Royale wolf population (11). The goal should be to recreate a well-connected metapopulation spanning Scandinavia and Finland with a genetically effective population size of over 500, in line with the proposed CBD indicator (12). Considerably more genetic exchange than the current one-migrant-per-generation aim is needed (3).
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| 9. |
- Vucetich, John A., et al.
(författare)
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The logic of persistence
- 2010
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 143:3, s. 533-534
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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