Limits...
Genetic variants associated with sleep disorders.

Kripke DF, Kline LE, Nievergelt CM, Murray SS, Shadan FF, Dawson A, Poceta JS, Cronin J, Jamil SM, Tranah GJ, Loving RT, Grizas AP, Hahn EK - Sleep Med. (2014)

Bottom Line: In aryl hydrocarbon receptor nuclear translocator-like (ARNTL), rs10766071 was associated with decreased polysomnographic sleep duration.SNPs in casein kinase 1 delta (CSNK1D rs11552085), cryptochrome 1 (CRY1 rs4964515), and retinoic acid receptor-related orphan receptor A (RORA rs11071547) were less persuasively associated with sleep latency and time of falling asleep.SNPs associated with several sleep phenotypes were suggested, but due to risks of false discovery, independent replications are needed before the importance of these associations can be assessed, followed by investigation of molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Viterbi Family Sleep Center, Scripps Clinic, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Electronic address: dkripke1@san.rr.com.

Show MeSH

Related in: MedlinePlus

Association of rs3923809 with the log10 periodic leg movement index. The association of rs3923809 genotypes with the leg movement index (log scale) is shown. The ordinate is the loglmindexp1, that is, LOG10[lmindex + 1], where lmindex is the leg movements per hour of sleep (plus 1). The error bars show the 95% confidence limits of the mean loglmindexp1. The horizontal axis specifies genotypes of rs3923809, with the number of DNA samples having each genotype in parenthesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4352103&req=5

Figure 4: Association of rs3923809 with the log10 periodic leg movement index. The association of rs3923809 genotypes with the leg movement index (log scale) is shown. The ordinate is the loglmindexp1, that is, LOG10[lmindex + 1], where lmindex is the leg movements per hour of sleep (plus 1). The error bars show the 95% confidence limits of the mean loglmindexp1. The horizontal axis specifies genotypes of rs3923809, with the number of DNA samples having each genotype in parenthesis.

Mentions: As previously reported [53], BTBD9 rs3923809 was associated with the leg movement indices with Bonferroni significance. The less common allele is associated with fewer leg movements (Fig. 4). BTBD9 rs3923809 was also nominally associated with polysomnographic total sleep time, sleep efficiency, and REM latency, all of which associations might be mediated by periodic limb movements causing sleep disturbance. Our findings partially replicate the previous reports of Stefansson et al. [53] and Winkelmann, et al. [54]. However, we did not replicate any association of rs3923809 with restless legs, nor could we replicate an association of any of five MAP2K5 SNPs with restless legs [54], an outcome rather similar to that in the Wisconsin cohort [55]. One limitation of our method was that we did not isolate an RLS subsample focused on those with familial RLS [56]. But our strategy was directed towards SNPs that would impact RLS susceptibility in a sleep clinic sample in which familiality was not a criterion. An association of MEIS1 rs6710341 with restless legs [57] was confirmed by the replication criterion of P < 0.05, but the association of rs2300478 [13] was not replicated in the questionnaire data. In a supplementary logistic regression based on physician recorded research diagnoses of restless legs syndrome (not shown), of the nine SNPs of BTBD9, MEIS1, and MAP2K examined for replication, only MEIS1 rs2300478 reached nominal significance (P < 0.05).


Genetic variants associated with sleep disorders.

Kripke DF, Kline LE, Nievergelt CM, Murray SS, Shadan FF, Dawson A, Poceta JS, Cronin J, Jamil SM, Tranah GJ, Loving RT, Grizas AP, Hahn EK - Sleep Med. (2014)

Association of rs3923809 with the log10 periodic leg movement index. The association of rs3923809 genotypes with the leg movement index (log scale) is shown. The ordinate is the loglmindexp1, that is, LOG10[lmindex + 1], where lmindex is the leg movements per hour of sleep (plus 1). The error bars show the 95% confidence limits of the mean loglmindexp1. The horizontal axis specifies genotypes of rs3923809, with the number of DNA samples having each genotype in parenthesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352103&req=5

Figure 4: Association of rs3923809 with the log10 periodic leg movement index. The association of rs3923809 genotypes with the leg movement index (log scale) is shown. The ordinate is the loglmindexp1, that is, LOG10[lmindex + 1], where lmindex is the leg movements per hour of sleep (plus 1). The error bars show the 95% confidence limits of the mean loglmindexp1. The horizontal axis specifies genotypes of rs3923809, with the number of DNA samples having each genotype in parenthesis.
Mentions: As previously reported [53], BTBD9 rs3923809 was associated with the leg movement indices with Bonferroni significance. The less common allele is associated with fewer leg movements (Fig. 4). BTBD9 rs3923809 was also nominally associated with polysomnographic total sleep time, sleep efficiency, and REM latency, all of which associations might be mediated by periodic limb movements causing sleep disturbance. Our findings partially replicate the previous reports of Stefansson et al. [53] and Winkelmann, et al. [54]. However, we did not replicate any association of rs3923809 with restless legs, nor could we replicate an association of any of five MAP2K5 SNPs with restless legs [54], an outcome rather similar to that in the Wisconsin cohort [55]. One limitation of our method was that we did not isolate an RLS subsample focused on those with familial RLS [56]. But our strategy was directed towards SNPs that would impact RLS susceptibility in a sleep clinic sample in which familiality was not a criterion. An association of MEIS1 rs6710341 with restless legs [57] was confirmed by the replication criterion of P < 0.05, but the association of rs2300478 [13] was not replicated in the questionnaire data. In a supplementary logistic regression based on physician recorded research diagnoses of restless legs syndrome (not shown), of the nine SNPs of BTBD9, MEIS1, and MAP2K examined for replication, only MEIS1 rs2300478 reached nominal significance (P < 0.05).

Bottom Line: In aryl hydrocarbon receptor nuclear translocator-like (ARNTL), rs10766071 was associated with decreased polysomnographic sleep duration.SNPs in casein kinase 1 delta (CSNK1D rs11552085), cryptochrome 1 (CRY1 rs4964515), and retinoic acid receptor-related orphan receptor A (RORA rs11071547) were less persuasively associated with sleep latency and time of falling asleep.SNPs associated with several sleep phenotypes were suggested, but due to risks of false discovery, independent replications are needed before the importance of these associations can be assessed, followed by investigation of molecular mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Viterbi Family Sleep Center, Scripps Clinic, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Electronic address: dkripke1@san.rr.com.

Show MeSH
Related in: MedlinePlus