Individuals with a later chronotype (evening types) tend to have unhealthier behaviors and increased morbidity and mortality as compared with those with an earlier chronotype (morning types). However, the role of genetics in explaining evening types’ adverse health and health behavior is unclear. Our aim was to study genetic associations of chronotype among 8433 Finns from the cross-sectional National FINRISK 2007 and 2012 studies. First, we studied associations between chronotype and 20 key clock genes with a candidate-gene approach and then performed a full genome-wide association study (GWAS) of chronotype. We also developed a genetic risk score (GRS) for chronotype based on 313 single nucleotide polymorphisms (SNPs) that have previously been associated with chronotype. Chronotype was assessed with a shortened version of Horne and Östberg’s Morningness-Eveningness Questionnaire (sMEQ), and for comparison, we also used the single self-evaluation question on chronotype from the questionnaire. Linear and logistic regression was used for statistical analysis assuming additive effects. The clock gene analysis revealed 1 independent association signal within NR1D2 (lead SNP rs4131403) that was associated with chronotype (p < 0.05; as based on both chronotype assessment methods). The GWAS analysis did not yield any genome-wide significant associations (p > 5 × 10⁻⁸). However, higher GRS was associated with evening chronotype (p < 0.001; as based on both chronotype assessment methods). In conclusion, our findings indicated novel genetic associations between chronotype and the NR1D2 clock gene, which has previously been associated with carbohydrate and lipid metabolism. Furthermore, the GRS was able to capture the genetic aspect of chronotype in our study population. These findings expand our knowledge of the genetic basis of chronotype.

与早睡型（早睡型）的人相比，晚睡型（晚装型）的人往往有更不健康的行为，发病率和死亡率也更高。然而，遗传学在解释夜间类型的不良健康和健康行为方面的作用尚不清楚。我们的目的是研究来自 2007 年和 2012 年全国 FINRISK 横断面研究的 8433 名芬兰人之间的时间型遗传关联。首先，我们使用候选基因方法研究了钟型与 20 个关键时钟基因之间的关联，然后进行了钟型的全基因组关联研究 (GWAS)。我们还开发了一个基于 313 个单核苷酸多态性 (SNP) 的基因风险评分 (GRS)，这些单核苷酸多态性 (SNP) 以前与睡眠类型相关。使用缩短版的 Horne 和 Östberg 的早晚问卷 (sMEQ) 评估了睡眠时间类型，为了进行比较，我们还使用了问卷中关于睡眠类型的单一自我评估问题。假设加性效应，线性和逻辑回归用于统计分析。时钟基因分析揭示了 1 个独立的关联信号NR1D2（先导 SNP rs4131403）与睡眠类型相关（p < 0.05；基于两种睡眠类型评估方法）。GWAS 分析没有产生任何全基因组显着关联（p > 5 × 10 ^-8）。然而，较高的 GRS 与夜间睡眠类型相关（p < 0.001；根据两种睡眠类型评估方法）。总之，我们的研究结果表明，睡眠型与NR1D2时钟基因之间存在新的遗传关联，该基因以前与碳水化合物和脂质代谢有关。此外，GRS 能够在我们的研究人群中捕捉到钟型的遗传方面。这些发现扩展了我们对计时型遗传基础的了解。