The genetic etiology of periodic limb movement in sleep

Study Objectives Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects. Methods The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization. Results We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 x 10(-12), beta = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14);and rs9369062 (p = 3.06 x 10(-22), beta = 0.2093), a SNP located in the intron region of BTBD9 (6p12);both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS. Conclusions Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings

Genetic risk for subjective reports of insomnia associate only weakly with polygraphic measures of insomnia in 2,770 adults

STUDY OBJECTIVES: Subjective insomnia complaints and objective sleep changes are mostly studied outside of clinical trial studies. In this study, we tested whether 240 genetic variants associated with subjectively reported insomnia were also associated with objective insomnia parameters extracted from polysomnographic recordings in three studies. METHODS: The study sample (total n = 2,770) was composed of the Wisconsin Sleep Cohort (n = 1,091) and the Osteoporotic Fractures in Men (n = 1,026) study, two population-based studies, and the Stanford Sleep Cohort, a sleep center patient-based sample (n = 653). Seven objective polysomnographic features related to insomnia defined outcome variables, with each variant allele serving as predictor. Meta-regression was performed, accounting for common confounders as well as variance differences between studies. Additionally, a normalized genetic risk score was generated for each subject to serve as a predictor variable in separate linear mixed models assessing objective insomnia features. RESULTS: After correction for multiple testing, single-nucleotide polymorphisms associated with subjective insomnia were not significantly associated with 6 of 7 objective sleep measures. Only periodic limb movement index was significantly associated with rs113851554 (MEIS1), as found in previous studies. The normalized genetic risk score was only weakly associated with arousal index and duration of wake after sleep onset. CONCLUSIONS: Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables. CITATION: Foldager J, Peppard PE, Hagen EW, et al. Genetic risk for subjective reports of insomnia associates only weakly with polygraphic measures of insomnia in 2,770 adults. J Clin Sleep Med. 2022;18(1):21–29

The genetic etiology of periodic limb movement in sleep.

Study objectivesPeriodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.MethodsThe MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.ResultsWe found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.ConclusionsBecause PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings

Factors Affecting the Successful Realisation of Benefits from Systems Development Projects: Findings from Three Case Studies

This article was published in the Journal of Information Technology [© Palgrave Macmillan] and the definitive version is available at: http://dx/doi.org/10.1057/jit.2011.8The return that organisations derive from investments in information systems and technology continues to disappoint. While there is a very significant body of literature on the factors that should facilitate a successful outcome from systems development, there is growing concern that these prescriptions are not having their desired effect. In this paper, we argue that the success of a systems development project should be measured in terms of its ability to deliver meaningful benefits, rather than the timely delivery of a technical artefact, and therefore organisations should adopt an explicit and proactive benefits realisation approach when investing in IT. Consequently, we sought to explore those actionable factors that might facilitate the effective realisation of benefits from systems development initiatives. Three organisations were identified that claimed to adopt a proactive approach to benefits realisation, and detailed studies of their systems development practices were conducted. Our analysis found that whilst one organisation had been successful in its adoption of a benefits realisation perspective, the other two had not, and this allowed us to identify those factors that helped to explain this difference in outcomes. In short, this paper makes an important contribution by identifying how a sub-set of traditional systems success factors might be enhanced, to give them a more explicit benefits realisation orientation. Moreover, it presents a coherent set of principles that can be used for deriving other factors and practices