Department of Psychology, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Department of Optometry and Visual Science, City University London, Northampton Square, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2024 Jul 1;65(8):24. doi: 10.1167/iovs.65.8.24.
Within the healthy population there is a large variation in the ability to perform smooth pursuit eye movements. Our purpose was to investigate the genetic and physiological bases for this variation.
We carried out a whole-genome association study, recording smooth pursuit movements for 1040 healthy volunteers by infrared oculography. The primary phenotypic measure was root mean square error (RMSE) of eye position relative to target position. Secondary measures were pursuit gain, frequency of catch-up saccades, and frequency of anticipatory saccades. Ten percent of participants, chosen randomly, were tested twice, giving estimates of test-retest reliability.
No significant association was found with three genes previously identified as candidate genes for variation in smooth pursuit: DRD3, COMT, NRG1. A strong association (P = 3.55 × 10-11) was found between RMSE and chromosomal region 1q42.2. The most strongly associated marker (rs701232) lies in an intron of KCNK1, which encodes a two-pore-domain potassium ion channel TWIK-1 (or K2P1) that affects cell excitability. Each additional copy of the A allele decreased RMSE by 0.29 standard deviation. When a psychophysical test of visually perceived motion was used as a covariate in the regression analysis, the association with rs701232 did not weaken (P = 5.38 × 10-12).
Variation in the sequence or the expression of the pH-dependent ion channel TWIK-1 is a likely source of variance in smooth pursuit. The variance associated with TWIK-1 appears not to arise from sensory mechanisms, because the use of a perceptual covariate left the association intact.
在健康人群中，平稳追踪眼球运动的能力存在很大差异。我们的目的是研究这种差异的遗传和生理基础。
我们进行了全基因组关联研究，通过红外眼动描记术记录了 1040 名健康志愿者的平稳追踪运动。主要表型测量指标是眼位相对于目标位置的均方根误差（RMSE）。次要测量指标包括追踪增益、捕获性跳跃的频率和预期性跳跃的频率。随机选择 10%的参与者进行两次测试，以估计测试-重测可靠性。
未发现与先前确定的三个候选基因（DRD3、COMT、NRG1）在平稳追踪中的变异有关的显著关联。在 RMSE 与 1q42.2 染色体区域之间发现了强烈的关联（P=3.55×10-11）。最相关的标记物（rs701232）位于 KCNK1 的内含子中，该基因编码双孔域钾离子通道 TWIK-1（或 K2P1），影响细胞兴奋性。每个 A 等位基因的额外拷贝使 RMSE 降低 0.29 个标准差。当将视觉感知运动的心理物理测试用作回归分析中的协变量时，与 rs701232 的关联并未减弱（P=5.38×10-12）。
pH 依赖性离子通道 TWIK-1 的序列或表达的变异可能是平稳追踪变异性的来源。与 TWIK-1 相关的变异似乎不是来自感觉机制，因为使用感知协变量保留了关联的完整性。
