Divergence of an association between depressive symptoms and a dopamine polygenic score in Caucasians and Asians
Divergence of an association between depressive symptoms and a dopamine polygenic score in Caucasians and Asians
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DOI：
10.1007/s00406-019-01040-x
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发表时间：
2020-03-01
影响因子：
4.7
通讯作者：
Hariri, Ahmad R.
中科院分区：
文献类型：
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作者：
Avinun, Reut;Nevo, Adam;Hariri, Ahmad R.
最近的一项研究报告了假定的功能性多巴胺 (DA) 多基因评分（指示较高水平的 DA 信号传导）与抑郁症状之间的负相关。我们尝试使用杜克大学神经遗传学研究的数据来复制这种关联。我们的复制尝试是在 520 名非西班牙裔白人志愿者（277 名女性，平均年龄 19.78 +/- 1.24 岁）的子样本中进行的。 DA 多基因评分基于以下五个位点：rs27072 (SLC6A3/DAT1)、rs4532 (DRD1)、rs1800497 (DRD2/ANKK1)、rs6280 (DRD3) 和 rs4680 (COMT)。由于原始研究中的发现样本主要由亚洲参与者组成，因此我们还对较小的亚洲志愿者子样本（N = 316，179 名女性，平均年龄 19.61 +/- 1.32 岁）进行了事后分析。在非西班牙裔白种人的主要样本中，控制性别、年龄、社会经济地位（SES）、体重指数、遗传血统以及早期和近期生活压力的线性回归分析显示，较高的 DA 多基因评分与较高的自我报告抑郁症状相关。这与最初的 DA 多基因评分较高和抑郁症状较低的关联形成鲜明对比。然而，我们的亚洲子样本中的关联方向与最初的发现一致。我们的结果还表明，与亚洲子样本相比，非西班牙裔白种人子样本的特征是社会经济地位较高、早期和近期生活压力较低以及抑郁症状较低。这些差异可能导致了所观察到的关联差异。总的来说，目前的研究结果增加了证据，表明特定的遗传关联可能在人群之间存在差异，并进一步鼓励在检查抑郁症状和抑郁症的多基因性质时建立明确的种族/民族模型。
A recent study reported a negative association between a putatively functional dopamine (DA) polygenic score, indexing higher levels of DA signaling, and depressive symptoms. We attempted to replicate this association using data from the Duke Neurogenetics Study. Our replication attempt was made in a subsample of 520 non-Hispanic Caucasian volunteers (277 women, mean age 19.78 +/- 1.24 years). The DA polygenic score was based on the following five loci: rs27072 (SLC6A3/DAT1), rs4532 (DRD1), rs1800497 (DRD2/ANKK1), rs6280 (DRD3), and rs4680 (COMT). Because the discovery sample in the original study consisted mostly of Asian participants, we also conducted a post hoc analysis in a smaller subsample of Asian volunteers (N = 316, 179 women, mean age 19.61 +/- 1.32 years). In the primary sample of non-Hispanic Caucasians, a linear regression analysis controlling for sex, age, socioeconomic status (SES), body mass index, genetic ancestry, and both early and recent life stress, revealed that higher DA polygenic scores were associated with higher self-reported symptoms of depression. This was in contrast to the original association of higher DA polygenic scores and lower depressive symptoms. However, the direction of the association in our Asian subsample was consistent with this original finding. Our results also suggested that compared to the Asian subsample, the non-Hispanic Caucasian subsample was characterized by higher SES, lower early and recent life stress, and lower depressive symptoms. These differences may have contributed to the observed divergence in associations. Collectively, the current findings add to evidence that specific genetic associations may differ between populations and further encourage explicit modeling of race/ethnicity in examining the polygenic nature of depressive symptoms and depression.