Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Eur Psychiatry. 2021 Oct 13;64(1):e61. doi: 10.1192/j.eurpsy.2021.2237.
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.
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.
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 → SCZvsBD = 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 (ORSCZvsBD → 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).
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.
智力与精神分裂症（SCZ）和双相情感障碍（BD）呈负相关；智力低下是病因还是结果尚不清楚。我们研究了智力与 SCZ 或 BD 风险以及 SCZ 和 BD 之间共享风险和 SCZ 特异性风险之间的因果关系。
为了估计潜在的因果关系，我们使用广义基于汇总数据的 Mendelian 随机化（GSMR）对多单核苷酸多态性（SNP）Mendelian 随机化（MR）进行了分析。利用五个 GWAS（智力、SCZ 与对照[CON]、BD 与 CON、SCZ+BD 与 CON 以及 SCZ 与 BD；样本量高达 269867）的汇总数据集进行了分析。
观察到 SCZ 和 BD 风险之间存在强烈的双向关联（比值比；ORSCZ→BD=1.47，p=2.89×10-41，ORBD→SCZ=1.44，p=1.85×10-52）。低智力与 SCZ 高风险呈双向相关，智力对 SCZ 风险的影响更强（OR 低智力→SCZ=1.62，p=3.23×10-14），而反之则较弱（ORSCZ→低智力=1.06，p=3.70×10-23）。此外，低智力会影响 SCZ 和 BD 之间的共享风险（OR 低智力→SCZ+BD=1.23，p=3.41×10-5）和 SCZ 特异性风险（OR 低智力→SCZvsBD=1.64，p=9.72×10-10）；共享风险（ORSCZ+BD→低智力=1.04，p=3.09×10-14）而不是 SCZ 特异性风险（ORSCZvsBD→低智力=1.00，p=0.88）对低智力的影响较弱。相反，智力与 BD 风险之间没有显著的因果关系（p>0.05）。
这些发现支持观察性研究，表明 SCZ 患者在发病前智力受损和智力下降。此外，SCZ 和 BD 之间的共同因素可能导致发病前智力受损和智力下降，但 SCZ 特异性因素可能受到发病前智力受损的影响。我们建议将具有这些遗传因素的患者归类为具有认知障碍的 SCZ 或 BD 亚型。
