Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Lee, Sang; Byrne, Enda M.; Wray, Naomi R.; Neale, Benjamin M.; Anttila, Verneri; Rossin, Lizzy; Daly, Mark J.; Ripke, Stephan; Ó'Dúshláine, Colm; Scolnick, Edward M.; McCarroll, Steven A.; Moran, Jennifer L.; Chambert, Kimberly; Purcell, Shaun; Ruderfer, Douglas M.; Sklar, Pamela; Lee, Sang Hyuck; Bergen, Sarah E.; Holmans, Peter; Gordon‐Smith, Katherine; Craddock, Nicholas; Georgieva, Lyudmila; Grozeva, Detelina; Jones, Ian D.; Hamshere, Marian L.; O‘Donovan, Michael; Owen, Michael J.; Thapar, Anita; Goddard, Michael E.; John, Esther M.; Absher, Devin; Myers, Richard M.; Agartz, Ingrid; Djurovic, Srdjan; Mattingsdal, Morten; Andreassen, Ole A.; Thompson, Robert C.; Watson, Stanley J.; Akil, Huda; Meng, Fan; Amin, Farooq; Melle, Ingrid; Krasucki, Robert; Anjorin, Adebayo; Choudhury, Khalid; Lawrence, Jacob; Gurling, Hugh; Pimm, Jonathan; Bass, Nicholas; Kandaswamy, Radhika; McQuillin, Andrew; Puri, Vinay; Kenny, Elaine; Corvin, Aiden; Cormican, Paul; Morris, Derek W.; Anney, Richard; Quinn, Emma M.; Donohoe, Gary; Gill, Michael; Gallagher, Louise; Arking, Dan E.

doi:10.1038/ng.2711

Nat Genet

2013

DOI: 10.1038/ng.2711

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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Sang Lee

¹

,

Enda M. Byrne

²

,

Naomi R. Wray

³

et al.

Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the esti… Show more

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Cited by 2,346 publications

(1,205 citation statements)

References 83 publications

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80

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1,110

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“…Significant correlations were found for several traits including schizophrenia 15 ( r G = 0.211, P = 1.03 × 10 −5 ) and measures of cognitive ability, especially educational attainment 20 ( r G = 0.199, P = 2.56 × 10 −9 ), indicating a substantial genetic overlap with these phenotypes and corroborating previous reports 5,66–68 . In contrast to previous reports 16 , we found a strong and highly significant correlation with major depression 21 ( r G = 0.412, P = 1.40 × 10 −25 ), and we report a prominent overlap with ADHD 69 ( r G = 0.360, P = 1.24 × 10 −12 ). Moreover, we confirm the genetic correlation with social communication difficulties at age 8 in a non-ASD population sample reported previously based on a subset of the ASD sample 70 ( r G = 0.375, P = 0.0028).…”

Section: Resultscontrasting

confidence: 99%

Identification of common genetic risk variants for autism spectrum disorder

Grove

¹

,

Ripke

²

,

Als

³

et al. 2019

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Significant correlations were found for several traits including schizophrenia 15 ( r G = 0.211, P = 1.03 × 10 −5 ) and measures of cognitive ability, especially educational attainment 20 ( r G = 0.199, P = 2.56 × 10 −9 ), indicating a substantial genetic overlap with these phenotypes and corroborating previous reports 5,66–68 . In contrast to previous reports 16 , we found a strong and highly significant correlation with major depression 21 ( r G = 0.412, P = 1.40 × 10 −25 ), and we report a prominent overlap with ADHD 69 ( r G = 0.360, P = 1.24 × 10 −12 ). Moreover, we confirm the genetic correlation with social communication difficulties at age 8 in a non-ASD population sample reported previously based on a subset of the ASD sample 70 ( r G = 0.375, P = 0.0028).…”

Section: Resultscontrasting

confidence: 99%

Identification of common genetic risk variants for autism spectrum disorder

Grove

¹

,

Ripke

²

,

Als

³

et al. 2019

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Second, contrary to the results of molecular genetic multivariate models, which placed bipolar disorder and schizophrenia in the same psychosis factor, and the many reports of schizophrenia–bipolar disorder genetic correlations in the range of 0.60 to 0.80 from molecular genetic studies, we found bipolar disorder to load on both the mood disorders and psychosis factor with the former loadings being stronger. However, our findings are consistent with most bipolar disorder family studies that show substantial increase in risk for major depression and more moderate increase in risk for schizophrenia .…”

Section: Discussioncontrasting

confidence: 99%

Structure of the Genetic Risks for Psychiatric Disorders in Swedish Population-Based Registries

Kendler

¹

,

Ohlsson

²

,

Sundquist

³

et al. 2026

JAMA Psychiatry

0

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Our results are also not consistent with recent reports of high genetic correlations between SZ and BD 16 , 17 , but are with earlier family studies 18 – 20 showing quite modest co-aggregation. While the FGRS score of BD is the second highest observed for SZ, it is much weaker, and the association is not reciprocal as the SZ FGRS is the eighth strongest FGRS for BD.…”

Section: Discussioncontrasting

confidence: 99%

The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample

Kendler

¹

,

Ohlsson

²

,

Sundquist

³

et al. 2021

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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