Genetic risk for bipolar disorder and psychopathology from childhood to early adulthood

Abstract

Background Studying the phenotypic manifestations of increased genetic liability for Bipolar Disorder (BD) can increase understanding of this disorder. Aims We assessed whether genetic risk for BD was associated with childhood psychopathology and features of hypomania in young adulthood within a large population-based birth cohort. Methods We used data from the second Psychiatric Genetics Consortium Genome Wide Association Study (GWAS) for Bipolar Disorder to construct a polygenic risk score (PRS) for each individual in the Avon Longitudinal Study of Parents and Children (ALSPAC). Linear and logistic regression models were used to assess associations between the BD-PRS and emotional/behavioural difficulties, attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) traits in childhood, as well as hypomania in early adulthood (sample sizes from 2,654 to 6,111). Results The BD-PRS was not associated with total hypomania score, but was weakly associated with a binary measure of hypomania (OR=1.13, 95%CI 0.98,1.32; p=0.097), and particularly at higher hypomania symptom thresholds (strongest evidence OR=1.33, 95%CI 1.07, 1.65; p=0.01). The BD-PRS was also associated with ADHD (OR=1.31, 95%CI 1.10, 1.57; p=0.018), but not with other childhood psychopathology. 3 Limitations The PRS only captures common genetic variation and currently explains a relatively small proportion of the variance for BD. Conclusions The BD-PRS was associated with ADHD in childhood, and weakly with adult hypomania, but not with other psychopathology examined. Our findings suggest that genetic risk for BD does not appear to manifest in childhood to the same extent as schizophrenia genetic risk has been reported to do.

Translating insights from neuropsychiatric genetics and genomics for precision psychiatry

“…To the extent that this may involve individuals without the disease in question, this mitigates the risk of reverse causation and drug effects, though other sources of confounding may not be excluded [106]. Samples such as the UK Biobank, the ALSPAC birth cohort, the ABCD study, and those available to the Enigma neuroimaging consortium are currently being explored in relation to genetic risk for psychiatric disorders [17,[107][108][109][110][111]. These studies can help identify endophenotypic markers of risk such as brain structure [112,113] and cognitive impairment [62,114] and developmental antecedents [115].…”

Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults

“…That is, a number of patients classified as having MDD in our sample might be misdiagnosed BD patients with undocumented/undetected hypomanic symptoms. However, a recent study showed that BD-PRS was not associated with hypomania (19). In addition, all subjects in our study were diagnosed by experienced raters with the semi-structured clinical interview SCID-I, which is a valid instrument to detect hypomania symptoms.…”

“…To date, few studies have investigated phenotypes associated with genetic risk of BD utilizing BD-PRS (19,54). In this study, we uniquely investigated the role of psychopathology and high-risk factors in young adults for the development of BD using BD-PRS scores.…”

“…ADHD has an earlier age of onset than BD and is common in relatives and offspring of individuals with BD, which has led to the hypothesis that it may be a precursor of BD (17,18). However, while there are inconsistent findings regarding a genetic overlap between ADHD and BD (19), recent studies assessing genetic correlations between large-scale genome-wide association studies (GWAS) indicate a modest but significant positive association (12,18,20).…”

Drug repositioning for psychiatric and neurological disorders through a network medicine approach

“…Network medicine 13 is an emerging field that combines systems biology and network science to understand how genes interact in disease and health. For PNDs, coexpression networks [14][15][16] and genome-wide association studies 9,17,18 have unraveled molecular mechanisms and genomic variations related to these disorders. Many more small-scale studies have investigated the roles of specific genes in PNDs.…”