Recent genome-wide association studies of mood instability (MOOD) have found significant positive genetic correlation with major depression (DEP) and weak correlations with other psychiatric disorders. We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. GWAS summary statistics for schizophrenia (SCZ, n = 105,318), bipolar disorder (BIP, n = 413,466), DEP (n = 450,619), attention-deficit hyperactivity disorder (ADHD, n = 53,293), and MOOD (n = 363,705) were analyzed using the bivariate causal mixture model and conjunctional false discovery rate methods. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (r_g = 0.10–0.62). Of 10.4 K genomic variants influencing MOOD, 4 K–9.4 K influenced psychiatric disorders. Furthermore, MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25. Fifty-three jointly associated loci were overlapping across two or more disorders, seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene-set, “synapse organization.” The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions may relate to differences in the core clinical features of each disorder.

中文翻译：

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情绪不稳定和精神疾病的共同遗传基础：跨性状全基因组关联分析

最近对情绪不稳定 (MOOD) 的全基因组关联研究发现，它与重度抑郁症 (DEP) 存在显着的正遗传相关性，而与其他精神疾病的相关性较弱。我们调查了 MOOD 和精神疾病之间的多基因重叠，超出了遗传相关性，以更好地描述假定的共享遗传决定因素。GWAS 精神分裂症（SCZ，n  = 105,318）、双相情感障碍（BIP，n  = 413,466）、DEP（n  = 450,619）、注意力缺陷多动障碍（ADHD，n  = 53,293）和情绪（n = 363,705) 使用双变量因果混合模型和联合错误发现率方法进行分析。情绪与所有精神疾病呈正相关，但强度差异很大 ( r _g = 0.10–0.62）。在影响 MOOD 的 10.4 K 基因组变异中，有 4 K–9.4 K 影响精神疾病。此外，MOOD 在 163 个位点与 DEP、110 个 SCZ、60 个 BIP 和 25 个 ADHD 联合相关。53 个联合相关位点在两种或多种疾病中重叠，其中 7 种对精神疾病的影响方向不一致。映射到与 MOOD 和所有四种疾病相关的基因座的基因在单个基因组“突触组织”中得到丰富。广泛的多基因重叠表明 MOOD 和精神疾病之间存在共同的分子基础。然而，遗传相关性和效应方向的不同模式可能与每种疾病的核心临床特征的差异有关。