Polygenic risk scores in bipolar disorder subgroups

Aminoff, Sofie Ragnhild; Tesli, Martin; Bettella, Francesco; Aas, Monica; Lagerberg, Trine Vik; Djurovic, Srdjan; Andreassen, Ole A.; Melle, Ingrid

doi:10.1016/j.jad.2015.05.021

Cited by 27 publications

(21 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence shows that the power to detect the genetic underpinnings of complex phenotypes increases with increasing sample sizes. Therefore, we assumed that, using an order of magnitude larger sample than in Aminoff et al., we might find an association between AAO and BD and SCZ . Based on the negative findings of our study, one can hypothesize that instead of being largely influenced by SNPs identified in GWASs of BD and SCZ, age at disease onset is rather influenced by other genetic, environmental or epigenetic risk factors.…”

Section: Discussionmentioning

confidence: 47%

“…Previous family studies support this hypothesis, as affected siblings of patients with early AAO were reported to be four times more likely to also have an early AAO, and children of couples with a positive history of affective disorders had a higher risk for an earlier AAO . However, a study conducted on 255 patients found no difference between the BD‐PRSs of the different AAO groups …”

Section: Discussionmentioning

confidence: 95%

“…For instance, genome‐wide complex trait analysis has shown that 79% of common variants are shared between BD and schizophrenia (SCZ) and that SCZ‐PRSs are good predictors of BD case‐control status . However, a single study thus far has investigated the association between the cumulative genomic risk for BD (BD‐PRS) and disease onset and found no significant results . The association with SCZ‐PRS has not been tested yet.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

et al. 2018

View full text Add to dashboard Cite

The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.

show abstract

Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…One previous study calculated GRS in subtypes of BP using a sample of 669 subjects (255 BP patients and 414 controls). Aminoff et al (2015) reported significantly higher scores for the BP patients than controls but no differences between the two BP subtypes (BP-I versus BP-II) based on the polygenic architecture. In the current study, our GRS analysis demonstrated clear seperation between BP-II patients and healthy controls in the discovery samples, and these results further validated in the replication samples.…”

Section: Discussionmentioning

confidence: 82%

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies

Kao

Chen

et al. 2016

IJNPPY

View full text Add to dashboard Cite

Background:This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II.Methods:We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways.Results:Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10–6), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10–3) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10–4~1.0×10–3) and replication samples (2.8×10–4~1.7×10–3). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II.Conclusion:We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II.

show abstract

“…Such a PRS might, in turn, be relevant to be studied in interaction with environmental risk factors that increase the susceptibility to the phenotype and/or the severity of the phenotype. Even though few studies have been published yet, it is suggested that a high PRS-BD might be associated with some indicators of the severity of the clinical expression in BD, such as the presence of psychotic features during mood episodes, 12,13 while PRS-BD has been suggested not to be associated with an earlier age at onset, another indicator of clinical severity. 14 Of note, interactions between PRS for several psychiatric disorders and childhood maltreatment have already been studied in a few psychiatric conditions, suggesting that this approach might be relevant for disentangling the determinants of mental disorders.…”

Section: Introductionmentioning

confidence: 99%

Childhood maltreatment and polygenic risk in bipolar disorders

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P = .01), especially when considering emotional abuse (rho = −0.16, P = .001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.

show abstract

Polygenic risk scores in bipolar disorder subgroups

Cited by 27 publications

References 43 publications

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies

Childhood maltreatment and polygenic risk in bipolar disorders

Contact Info

Product

Resources

About