Replication of Genome-Wide Association Studies (GWAS) loci for sleep in the British G1219 cohort

Sleep is a critical behavior shared by most higher animals. Sleep disturbances are comorbid with numerous psychiatric disorders, most notably symptoms of depression. Twin studies have suggested that genetic influences partially underlie the variation seen for numerous sleep-related traits across individuals. Recently, two Genome-Wide Association Studies (GWAS) conducted for sleep traits have revealed new candidate genes for sleep-related measures. We attempted to replicate the two most significant associations from these two studies, CACNA1C (a l-type calcium channel) with sleep latency and quality and ABCC9 (an ATP-sensitive potassium channel) with sleep duration, using the G1219 British population sample. We genotyped single-nucleotide polymorphisms (SNPs) for each of the two different sleep GWAS loci. Linear regression analyses were conducted to assess main effects of these SNPs on their corresponding sleep measures, as well as for depressive symptoms. We successfully replicated an association of a genetic variant in the CACNA1C gene (rs16929277) with sleep quality using an additive model of inheritance. A significant association of the ABCC9 gene (rs11046209) with sleep duration was seen only in a recessive models based upon a rare homozygous genotype (n = 2). There was also a significant association between a different ABCC9 gene variant (rs11046205) and depressive symptoms. These findings add further support for the involvement of calcium channels in the mechanisms regulating sleep function and suggest a possible role of the ABCC9 gene in depression