Kouakou Manuela R, Cabrera-Mendoza Brenda, Pathak Gita A, Cannon Tyrone D, Polimanti Renato
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA.
Schizophr Bull. 2024 Dec 20;51(1):85-94. doi: 10.1093/schbul/sbae093.
Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ.
We investigated genome-wide datasets related to SCZ (52 017 cases and 75 889 controls) from the Psychiatric Genomics Consortium, household income (HI; N = 361 687) from UK Biobank, and 2202 medical endpoints assessed in up to 342 499 FinnGen participants. A phenome-wide genetic correlation analysis of SCZ and HI was performed, also assessing whether SCZ genetic correlations were influenced by the HI effect on SCZ. Additionally, SCZ and HI direct effects on medical endpoints were estimated using multivariable Mendelian randomization (MR).
SCZ and HI showed overlapping genetic correlations with 70 traits (P < 2.89 × 10-5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, and musculoskeletal phenotypes. SCZ genetic correlations with these traits were not affected by the HI effect on SCZ. Considering Bonferroni multiple testing correction (P < 7.14 × 10-4), MR analysis indicated that SCZ and HI may affect medical abortion (SCZ OR = 1.07; HI OR = 0.78), panic disorder (SCZ OR = 1.20; HI OR = 0.60), personality disorders (SCZ OR = 1.31; HI OR = 0.67), substance use (SCZ OR = 1.2; HI OR = 0.68), and adjustment disorders (SCZ OR = 1.18; HI OR = 0.78). Multivariable MR analysis confirmed that SCZ effects on these outcomes were independent of HI.
The effect of SCZ genetic liability on mental and physical health may not be strongly affected by socioeconomic differences. This suggests that SCZ-specific strategies are needed to reduce negative health outcomes affecting patients and high-risk individuals.
精神分裂症患者常伴有多种共病，这显著缩短了他们的预期寿命。社会经济不平等可能是导致许多与精神分裂症相关的负面健康结果的原因。
我们研究了来自精神病基因组学联盟的与精神分裂症相关的全基因组数据集（52017例病例和75889例对照）、英国生物银行的家庭收入（HI；N = 361687）以及在多达342499名芬兰基因研究参与者中评估的2202个医学终点。对精神分裂症和家庭收入进行了全表型组遗传相关性分析，还评估了精神分裂症的遗传相关性是否受家庭收入对精神分裂症的影响。此外，使用多变量孟德尔随机化（MR）估计了精神分裂症和家庭收入对医学终点的直接影响。
精神分裂症和家庭收入与70种性状存在重叠的遗传相关性（P < 2.89×10⁻⁵），包括心理健康、物质使用、胃肠道疾病、生殖结局、肝脏疾病、呼吸系统问题和肌肉骨骼表型。精神分裂症与这些性状的遗传相关性不受家庭收入对精神分裂症的影响。考虑到Bonferroni多重检验校正（P < 7.14×10⁻⁴），MR分析表明，精神分裂症和家庭收入可能影响药物流产（精神分裂症OR = 1.07；家庭收入OR = 0.78）、惊恐障碍（精神分裂症OR = 1.20；家庭收入OR = 0.60）、人格障碍（精神分裂症OR = 1.31；家庭收入OR = 0.67）、物质使用（精神分裂症OR = 1.2；家庭收入OR = 0.68）和适应障碍（精神分裂症OR = 1.18；家庭收入OR = 0.78）。多变量MR分析证实，精神分裂症对这些结局的影响独立于家庭收入。
精神分裂症遗传易感性对身心健康的影响可能不受社会经济差异的强烈影响。这表明需要采取针对精神分裂症的特定策略来减少影响患者和高危个体的负面健康结果。
