PKU-IDG/McGovern Institute for Brain Research, and Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China.
Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 210029, Nanjing, China.
Eur J Hum Genet. 2019 Dec;27(12):1867-1875. doi: 10.1038/s41431-019-0478-2. Epub 2019 Jul 30.
Contour integration, a key visual function to deal with occlusion and discontinuity in natural scenes, is essential to human survival. However, individuals are not equally well equipped with this ability. In particular, contour integration deficiencies are commonly detected in patients with mental disorders, especially schizophrenia. To understand the underlying sources of these individual differences, the current study investigated the genetic basis of contour integration in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background. Quantitative genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphisms (SNPs) and association testing at SNP, gene, and pathway levels. Heritability estimation showed that common SNPs contributed 49.5% (standard error of the mean = 15.6%) of overall phenotypic variation, indicating moderate heritability of contour integration. Two-stage genome-wide association analysis (GWAS) detected four SNPs reaching genome-wide significance in the discovery test (N = 1931) but not passing the replication test (N = 688). Gene-level analysis further revealed a significant genome-wide association of a microRNA-encoding gene MIR1178 in both the discovery and replication cohorts. Another gene poly(A)-binding protein nuclear 1 like, cytoplasmic (PABPN1L) showed suggestive significance in the discovery cohort (p < 1 × 10) and was replicated in the replication cohort (p = 0.009). The pathway analysis did not detect any significant pathway. Taken together, this study identified significant gene associations with contour integration and provided support for a genetic transmission of the ability to perceive continuous contours in the environment.
轮廓整合是一种处理自然场景中遮挡和不连续性的关键视觉功能，对人类的生存至关重要。然而，个体在这方面的能力并不完全相同。特别是，在精神障碍患者中，尤其是精神分裂症患者中，经常会发现轮廓整合缺陷。为了了解这些个体差异的潜在来源，本研究调查了人类轮廓整合的遗传基础。共有 2619 名正常参与者接受了一项测试，即在杂乱背景中检测嵌入的连续轮廓的能力。进行了定量基因组分析，涉及基于单核苷酸多态性 (SNP) 的遗传力估计和 SNP、基因和途径水平的关联测试。遗传力估计表明，常见的 SNP 对总表型变异的贡献为 49.5%（平均值的标准误差为 15.6%），表明轮廓整合具有中度遗传力。两阶段全基因组关联分析 (GWAS) 在发现测试（N=1931）中检测到四个达到全基因组显著水平的 SNP，但在复制测试（N=688）中未通过。基因水平分析进一步揭示了 microRNA 编码基因 MIR1178 在发现和复制队列中都具有显著的全基因组关联。另一个基因 poly(A)-binding protein nuclear 1 like, cytoplasmic (PABPN1L) 在发现队列中表现出显著的意义（p<1×10），并在复制队列中得到复制（p=0.009）。通路分析未检测到任何有意义的通路。综上所述，本研究确定了与轮廓整合相关的显著基因关联，并为感知环境中连续轮廓的能力的遗传传递提供了支持。
