Genetic overlap between epilepsy and schizophrenia: Evidence from cross phenotype analysis in Hong Kong Chinese population

Gui, Hongsheng; Li, Miaoxin; Sham, Pak C.; Baum, Larry; Kwan, Patrick; Cherny, Stacey S.

doi:10.1002/ajmg.b.32607

Cited by 5 publications

(3 citation statements)

References 39 publications

(40 reference statements)

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“…Previous studies looking for shared genetic links between epilepsy and common genetic comorbidities, using either LDSC 17 or PRS 48 did not identify any shared polygenic signals between epilepsy and its common psychiatric comorbidities 15 . In the study of Gui and colleagues from Hong Kong, the lack of genetic overlap could reflect limited study power for discovery (n=522 epilepsy cases, n=377 schizophrenia cases).…”

Section: Discussionmentioning

confidence: 87%

Polygenic risk score analysis reveals shared genetic burden between epilepsy and psychiatric comorbidities

Campbell¹,

Lewis-Smith

Leu

et al. 2023

Preprint

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Background: One in three people with epilepsy experiences psychiatric comorbidity, with higher rates in people with drug-resistant epilepsy. Despite their high heritabilities, finding genetic links between epilepsy and psychiatric disorders has proven difficult. We used polygenic risk scoring (PRS) to test whether people with epilepsy have an increased polygenic burden of common genetic variants for depression, anxiety, psychosis, and attention deficit/hyperactivity disorder (ADHD), and examined whether such polygenic burden influences the response to pharmacological treatment of epilepsy. Methods: Phenotype data in the UK Biobank were assessed to identify people with 1) epilepsy (n=8 488), 2) depression (n=143 440), 3) psychosis (n=2 357), 4) ADHD (n=89), and 5) anxiety (n=18 222. Using genotype data and restricting to Caucasian-ancestry samples (n=409 634), PRS for each psychiatric trait were calculated and multinomial regression was used to compare 1) population controls, 2) people with epilepsy and no psychiatric illness, 3) people with epilepsy and the psychiatric trait of interest, and 4) people with the psychiatric trait of interest and no epilepsy. Fixed-effect meta-analysis was used to compare psychiatric PRS in drug-resistant and drug-responsive epilepsy samples from the UK Biobank (n=1 640) and the EpiPGX consortium (n=3 449). Results: After correction for multiple testing, people with epilepsy showed elevated PRS for depression (p<2 x10-16), psychosis (p=0.04) and ADHD (p<0.001). Patients with drug-resistant epilepsy had an increased PRS for psychosis (p=0.002) and depression (p=0.0004) relative to responsive cases. Conclusions: We present evidence that the common genetic basis of epilepsy overlaps with that of psychiatric conditions which are frequently comorbid in people with epilepsy. Common genetic variants that drive psychiatric illness are enriched in people with drug-resistant epilepsy. These results further our understanding of the genetic architecture of epilepsy and suggest a potential future role for polygenic interpretation of common variants in prognostic stratification, both for seizure-treatment outcomes and non-seizure comorbidities.

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Section: Discussionmentioning

confidence: 87%

Polygenic risk score analysis reveals shared genetic burden between epilepsy and psychiatric comorbidities

Campbell¹,

Lewis-Smith

Leu

et al. 2023

Preprint

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“…PRS analysis has been applied to identify whether schizophrenia-derived PRS could predict casecontrol status in a Hong-Kong based epilepsy cohort, and whether epilepsy PRS (derived from the first ILAE meta-analysis of mostly European epilepsy cases, ILAE 2014) could predict schizophrenia status in a Hong-Kong schizophrenia cohort. It was found that PRS was not predictive, in either direction (Gui et al, 2018). This could be due to the limited power of the first ILAE meta-analysis to detect epilepsy variants confer risk across ethnicities, or an indication that the common genetic architecture of epilepsy and schizophrenia are relatively exclusive.…”

Section: Examining the Genetic Overlap Between Epilepsy And Psychiatr...mentioning

confidence: 98%

Exploring the genetic overlap between psychiatric illness and epilepsy: A review

Campbell

Cavalleri

Delanty

2020

Epilepsy & Behavior

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“…Likewise, an association with SCZ (3.96 × 10 -5 and 2.44 × 10 -5 ) and MDD ( p = 0.0144 and 0.0314) were identified. A number of studies demonstrating similar genetic overlap between other combinations of mental, medical, and neurologic disorders have also recently appeared 11– 23 .…”

Section: Shared Individual Variantsmentioning

confidence: 99%

Shared Genetics of Psychiatric Disorders

Fuller

Reus

2019

F1000Res

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Until recently, advances in understanding the genetic architecture of psychiatric disorders have been impeded by a historic, and often mandated, commitment to the use of traditional, and unvalidated, categorical diagnoses in isolation as the relevant phenotype. Such studies typically required lengthy structured interviews to delineate differences in the character and duration of behavioral symptomatology amongst disorders that were thought to be etiologic, and they were often underpowered as a result. Increasing acceptance of the fact that co-morbidity in psychiatric disorders is the rule rather than the exception has led to alternative designs in which shared dimensional symptomatology is analyzed as a quantitative trait and to association analyses in which combined polygenic risk scores are computationally compared across multiple traditional categorical diagnoses to identify both distinct and unique genetic and environmental elements. Increasing evidence that most mental disorders share many common genetic risk variants and environmental risk modifiers suggests that the broad spectrum of psychiatric pathology represents the pleiotropic display of a more limited series of pathologic events in neuronal development than was originally believed, regulated by many common risk variants and a smaller number of rare ones.

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Genetic overlap between epilepsy and schizophrenia: Evidence from cross phenotype analysis in Hong Kong Chinese population

Cited by 5 publications

References 39 publications

Polygenic risk score analysis reveals shared genetic burden between epilepsy and psychiatric comorbidities

Polygenic risk score analysis reveals shared genetic burden between epilepsy and psychiatric comorbidities

Exploring the genetic overlap between psychiatric illness and epilepsy: A review

Shared Genetics of Psychiatric Disorders

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