Cross-disorder analysis of schizophrenia and 19 immune diseases reveals genetic correlation
Notice bibliographique
Résumé
Abstract Epidemiological studies indicate that many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenotypic correlation between immune diseases and schizophrenia might be explained by shared genetic risk factors ( genetic correlation ). We used data from a large genome-wide association study (GWAS) of schizophrenia (N=35,476 cases and 46,839 controls) to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we evaluated the association with schizophrenia of 581 variants previously reported to be associated with immune diseases at genome-wide significance. We identified three variants with pleiotropic effects, located in regions associated with both schizophrenia and immune disease. Our analyses provided the strongest evidence of pleiotropy at rs1734907 (∼85kb upstream of EPHB4 ), a variant which was associated with increased risk of both Crohn’s disease (OR = 1.16, P = 1.67×10 −13 ) and schizophrenia (OR = 1.07, P = 7.55×10 −6 ). Next, we investigated genome-wide sharing of common variants between schizophrenia and immune diseases using polygenic risk scores (PRS) and cross-trait LD Score regression (LDSC). PRS revealed significant genetic overlap with schizophrenia for narcolepsy (p=4.1×10 −4 ), primary biliary cirrhosis (p=1.4×10 −8 ), psoriasis (p=3.6×10 −5 ), systemic lupus erythematosus (p=2.2×10 −8 ), and ulcerative colitis (p=4.3×10 −4 ). Genetic correlations between these immune diseases and schizophrenia, estimated using LDSC, ranged from 0.10 to 0.18 and were consistent with the expected phenotypic correlation based on epidemiological data. We also observed suggestive evidence of sex-dependent genetic correlation between schizophrenia and multiple sclerosis (interaction p=0.02), with genetic risk scores for multiple sclerosis associated with greater risk of schizophrenia among males but not females. Our findings suggest that shared genetic risk factors contribute to the epidemiological co-occurrence of schizophrenia and certain immune diseases, and suggest that in some cases this genetic correlation is sex-dependent. Author Summary Immune diseases occur at different rates among patients with schizophrenia compared to the general population. While the reasons for this phenotypic correlation are unclear, shared genetic risk ( genetic correlation ) has been proposed as a contributing factor. Prior studies have estimated the genetic correlation between schizophrenia and a handful of immune diseases, with conflicting results. Here, we performed a comprehensive cross-disorder investigation of schizophrenia and 19 immune diseases. We identified three individual genetic variants associated with both schizophrenia and immune diseases, including a variant near EPHB4 – a gene whose protein product guides the migration of lymphocytes towards infected cells in the immune system and the migration of neuronal axons in the brain. We demonstrated significant genome-wide genetic correlation between schizophrenia and narcolepsy, primary biliary cirrhosis, psoriasis, systemic lupus erythematosus, and ulcerative colitis. Finally, we identified a potential sex-dependent pleiotropic effect between schizophrenia and multiple sclerosis. Our findings point to shared genetic risk for schizophrenia and at least a subset of immune diseases, which likely contributes to their epidemiological co-occurrence. These results raise the possibility that the same genetic variants may exert their effects on neurons or immune cells to influence the development of psychiatric and immune disorders, respectively.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».