全基因组关联研究在非焦虑个体中鉴定出抑郁症的新风险位点。
Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression.
机构信息
Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an710061, China.
Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
出版信息
Eur Psychiatry. 2022 Jun 22;65(1):e38. doi: 10.1192/j.eurpsy.2022.32.
BACKGROUND
Depression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC).
METHODS
The GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS.
RESULTS
Two genome-wide significant loci for non-anxiety depression were identified: rs139702470 ( = 1.54 × 10, OR = 0.29) locate in , and rs6046722 ( = 2.52 × 10, OR = 1.09) locate in These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 ( = 0.02, = 2.71 × 10) in , and rs11661122 ( = 8.16 × 10, = 8.08 × 10) in LDSC identified 19 traits genetically associated with non-anxiety depression ( < 0.001), such as marital separation/divorce ( = 0.45, SE = 0.15).
CONCLUSIONS
Our findings provide novel clues for understanding of the complex genetic architecture of depression.
背景
抑郁症是一种使人虚弱的精神障碍，常与焦虑并存。抑郁症和焦虑症的遗传机制有很大的重叠，研究非焦虑样本中的抑郁症有助于发现新的基因。我们使用全基因组关联研究（GWAS）和连锁不平衡得分回归（LDSC）评估非焦虑样本中抑郁症的遗传变异。
方法
使用英国生物库样本进行抑郁症评分和自我报告抑郁症的 GWAS，其中分别包含 99178 名焦虑评分<5 的非焦虑参与者和 86503 名无自我报告焦虑的非焦虑参与者。然后使用精神疾病基因组学联盟（PGC）的两项大型抑郁症 GWAS 汇总数据进行复制分析。最后，使用基于主要 GWAS 的 855 种与健康相关的特征，使用 LDSC 评估遗传相关性。
结果
确定了两个与非焦虑性抑郁症相关的全基因组显著位点：rs139702470（=1.54×10，OR=0.29）位于 ，rs6046722（=2.52×10，OR=1.09）位于 。这些关联基因在 PGC 的两项抑郁症 GWAS 中得到了复制，例如 rs1040582（=0.02，=2.71×10）在 ，rs11661122（=8.16×10，=8.08×10）在 。LDSC 确定了 19 个与非焦虑性抑郁症具有遗传相关性的特征（<0.001），例如婚姻分离/离婚（=0.45，SE=0.15）。
结论
我们的研究结果为理解抑郁症的复杂遗传结构提供了新的线索。
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