Mood instability (MOOD) is a transdiagnostic phenomenon with a prominent neurobiological basis. Recent genome-wide association studies found significant positive genetic correlation between MOOD and 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. 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 analysed using the bivariate causal mixture model and conjunctional false discovery rate methods to estimate the proportion of shared variants influencing MOOD and each disorder, and identify jointly associated genomic loci. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (rg=0.10-0.62). Of 10.4K genomic variants influencing MOOD, 4K-9.4K were estimated to influence psychiatric disorders. MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25, with consistent genetic effects in independent samples. Fifty-three jointly associated loci were overlapping across two or more disorders (transdiagnostic), 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 of shared loci suggest divergent effects on corresponding neurobiological mechanisms which may relate to differences in the core clinical features of each disorder.

中文翻译：

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全基因组关联分析揭示了情绪不稳定和精神疾病之间广泛的遗传重叠，但遗传效应的不同模式

情绪不稳定 (MOOD) 是一种具有显着神经生物学基础的跨诊断现象。最近的全基因组关联研究发现，情绪与重度抑郁症 (DEP) 之间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。我们调查了情绪和精神疾病之间的多基因重叠超出遗传相关性，以更好地表征假定的共享遗传决定因素。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 MOOD (n=363,705) 的汇总统计数据为使用双变量因果混合模型和连接错误发现率方法进行分析，以估计影响情绪和每种疾病的共享变体的比例，并识别共同相关的基因组位点。情绪与所有精神疾病呈正相关，但强度差异很大（rg = 0.10-0.62）。在影响情绪的 10.4K 基因组变异中，估计有 4K-9.4K 会影响精神疾病。MOOD 与 DEP 的 163 个基因座、SCZ 的 110 个、BIP 的 60 个和 ADHD 的 25 个共同相关，在独立样本中具有一致的遗传效应。五十三个联合相关的基因座在两种或多种疾病（跨诊断）中重叠，其中七个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集、突触组织中富集。广泛的多基因重叠表明情绪和精神疾病有共同的分子基础。然而，