Causal associations of intelligence with schizophrenia and bipolar disorder: A Mendelian randomization analysis. Issue 1 (13th October 2021)

• Record Type: Journal Article
• Authors: Ohi, Kazutaka; Takai, Kentaro; Kuramitsu, Ayumi; Sugiyama, Shunsuke; Soda, Midori; Kitaichi, Kiyoyuki; Shioiri, Toshiki
• Is Part Of: European psychiatry. Volume 64:Issue 1(2021)
• Publication Date: 2021-10-13
• Subjects: Bipolar disorder -- GWAS -- intelligence -- Mendelian randomization -- schizophrenia -- SNP; Psychiatry -- Periodicals; Mental illness -- Periodicals; Electronic journals; 616.89
• DOI: 10.1192/j.eurpsy.2021.2237
• Languages: English
• ISSNs: 0924-9338

Abstract

Abstract: Background: Intelligence is inversely associated with schizophrenia (SCZ) and bipolar disorder (BD); it remains unclear whether low intelligence is a cause or consequence. We investigated causal associations of intelligence with SCZ or BD risk and a shared risk between SCZ and BD and SCZ-specific risk. Methods: To estimate putative causal associations, we performed multi-single nucleotide polymorphism (SNP) Mendelian randomization (MR) using generalized summary-data-based MR (GSMR). Summary-level datasets from five GWASs (intelligence, SCZ vs. control [CON], BD vs. CON, SCZ + BD vs. CON, and SCZ vs. BD; sample sizes of up to 269, 867) were utilized. Results: A strong bidirectional association between risks for SCZ and BD was observed (odds ratio; ORSCZ → BD = 1.47, p = 2.89 × 10 −41, ORBD → SCZ = 1.44, p = 1.85 × 10 −52 ). Low intelligence was bidirectionally associated with a high risk for SCZ, with a stronger effect of intelligence on SCZ risk (ORlower intelligence → SCZ = 1.62, p = 3.23 × 10 −14 ) than the reverse (ORSCZ → lower intelligence = 1.06, p = 3.70 × 10 −23 ). Furthermore, low intelligence affected a shared risk between SCZ and BD (OR lower intelligence → SCZ + BD = 1.23, p = 3.41 × 10 −5 ) and SCZ-specific risk (ORlower intelligence → SCZ vs BD = 1.64, p = 9.72 × 10 −10 ); the shared risk (ORSCZ + BD → lower intelligence = 1.04, p = 3.09 × 10 −14 ) but not SCZ-specific risk (ORSCZ vs BD → lower intelligence = 1.00, p = 0.88) weakly affected low intelligence. Conversely, there was no significant causal association between intelligence and BD risk ( p > 0.05). Conclusions: These findings support observational studies showing that patients with SCZ display impairment in premorbid intelligence and intelligence decline. Moreover, a shared factor between SCZ and BD might contribute to impairment in premorbid intelligence and intelligence decline but SCZ-specific factors might be affected by impairment in premorbid intelligence. We suggest that patients with these genetic factors should be categorized as having a cognitive disorder SCZ or BD subtype.