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This is an open access article distributed under the terms GhzaAlah the Creative Commons Attribution License http: Numerous studies suggest genetic influences Sex extreme Al GhazAlah sleepiness and circadian rhythms.

More than participants were genotyped using the Affymetrix K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits. Sleepiness defined as the Epworth Sleepiness Scale scoreusual bedtime and usual sleep duration were assessed by self-completion questionnaire.

Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance Girls singles Bloomington xxx linkage analysis was performed. Heritability of sleepiness was 0. Sex extreme Al GhazAlah

Both genotype and Free sex Bastrop phenotype data were available for subjects. These peaks include Sex extreme Al GhazAlah candidate sleep-related genes, including CSNK2A2encoding a known component of the circadian molecular clock, and PROK2encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus.

Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of Sex extreme Al GhazAlah minor allele of this SNP was associated with a 15 minute later mean bedtime. Full association results are posted at http: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration.

Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes.

Sleepiness is a major cause of motor vehicle and occupational accidents, impaired social function, and reduced quality of life. Within individuals, the level of sleepiness is modulated by a combination of homeostatic duration of wakefulness and circadian time of day factors [ 2 ]. While behavioral factors and sleep disorders contribute to daytime sleepiness, there is great individual variability in the susceptibility to sleepiness in the context of disorders of sleep fragmentation [ 3 ] or sleep deprivation [ 4 ], which appears to be a stable individual trait.

Evidence from several studies indicates Sex extreme Al GhazAlah excessive sleepiness is heritable, with heritability estimates from recent twin studies in the range of 0. However, individual differences in diurnal preference Sex extreme Al GhazAlah types or "larks" versus evening types or "owls" have important implications for work scheduling and performance that are highly relevant in an economy in which almost one-fifth of employees are engaged in shift work [ 9 ].

Hot wife looking casual sex Columbia Maryland twin Sex extreme Al GhazAlah family studies suggest that diurnal preference is heritable, with heritability estimates of 0.

Usual sleep duration is an important determinant of daytime sleepiness; moreover, both short and long sleep duration have been associated in numerous epidemiologic studies with hypertension [ Sex extreme Al GhazAlah ], diabetes mellitus [ Ghazlah Sex extreme Al GhazAlah, 15 ], coronary heart disease [ 16 ] and mortality [ 17 - 19 ], although the mechanisms underlying these associations are poorly understood. Significant heritability of usual sleep duration has been reported, with heritability estimates of 0.

While sleepiness, diurnal preference, and sleep duration have long been recognized as heritable traits, the genetic basis of this heritability is largely unknown. While it has been suggested that heritability of sleepiness may reflect genetic influences on sleep-disordered breathing [ 5 ], sleep Wewahitchka FL adult personals is itself a highly regulated phenomenon and may be influenced by variations in the numerous genes involved in the circadian and homeostatic regulation of sleep and wakefulness.

For example, a polymorphism in the gene encoding adenosine deaminase is Sex extreme Al GhazAlah associated with an increase in slow-wave sleep, a marker of homeostatic sleep drive [ 21 ]. Polymorphisms in the human period 2 Sex extreme Al GhazAlah and casein kinase 1d CSNK1D genes, known elements of the circadian molecular clock, are associated with autosomal dominant advanced sleep phase syndrome in isolated families [ 2526 ].

A polymorphism in the 3'-untranslated region of the CLOCK gene has been inconsistently reported in association with evening preference [ 27 - 29 ] and a length polymorphism in a tandem repeat region of the period 3 protein, containing either 4 or 5 Sex extreme Al GhazAlah of an amino acid motif, is reportedly associated with diurnal preference [ 30 ]. These examples notwithstanding, it appears that sleepiness and diurnal preference are polygenic traits.

We are unaware of any published genome-wide linkage or association studies of daytime sleepiness, diurnal preference, or sleep duration in humans. The present study takes advantage of sleep phenotype data collected by the Sex extreme Al GhazAlah Heart Study at the Offspring Cycle 6 Examination. These data include measures of daytime sleepiness, usual bedtime, usual sleep duration, and sleep-disordered breathing. The aims of this study were to replicate, in this unselected family-based sample, prior reports of heritability of these traits and to conduct genome-wide linkage and association studies of these traits.

Although sleep phenotype data were collected from fewer than half of all Offspring participants, heritability of the sleep-related phenotypes was confirmed in this sample and preliminary linkage and association studies identified several loci of interest. Subjects of this study are drawn from the Framingham Offspring Study participants who completed sleep habits questionnaires between and Offspring Examination Cycle 6 for the Sleep Sex extreme Al GhazAlah Health Study, a longitudinal study of the cardiovascular consequences of sleep-disordered breathing that has been described elsewhere [ 32 ].

Of these subjects, members of pedigrees had biological relatives with valid sleep phenotype data and thus contributed to the heritability analyses. A maximum of members of families contributed informative data to each of the Sex extreme Al GhazAlah association analyses of sleep phenotypes.

Data Sex extreme Al GhazAlah daytime sleepiness, usual bedtime, and usual sleep Sex extreme Al GhazAlah were obtained from a self-completion questionnaire either handed to the participant at the time of a regularly scheduled visit to the Framingham Study clinic or mailed to the participant.

Sleepiness was defined as the score on the Epworth Sleepiness Scale, a widely used and well validated 8-item questionnaire that asks the likelihood of falling asleep in lA variety of commonly encountered situations [ 3435 ]. Usual bedtime was obtained from the single question, "What time to you usually go to bed on weeknights or work nights?

Data on work shift and retirement status were not available in this cohort; therefore, Girls in Covington seeking guys for phone sex order to exclude subjects in whom night shift work might lead to spurious estimates of circadian phenotype, the 0.

Those whose usual bedtime extreke by more than two hours between weekdays and weekends 1.

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Similarly, those whose usual sleep duration differed by more than two hours between Best pussy Barnstable and weekends 4.

As sleepiness, bedtime, and sleep duration may be influenced by age, sex and BMI [ 51020 ], adjustment for these Sex extreme Al GhazAlah was made by linear regression. Standardized residuals of the adjusted sleep phenotype variables were used in genetic analyses.

As further adjustment of sleepiness for usual sleep duration or self-reported symptoms of sleep-disordered breathing snoring, nocturnal breathing pauses reduced sample size but had Sex extreme Al GhazAlah impact on the linkage and association results, analyses using these further adjustments are not presented.

Heritability, linkage and Sex extreme Al GhazAlah association analysis xetreme performed as described in the Framingham Heart Study K Project Overview [ 33 ]. Briefly, multipoint linkage analysis was implemented using Merlin identity-by-descent estimates and variance extfeme linkage in SOLAR with a subset of 10, SNPs supplementing microsatellite markers from a previous genome scan.

All association tests employed an additive model. Reported association test results are limited to SNPs located on autosomes and meeting the following quality control criteria: Of the 70, SNPs meeting these criteria, 40, were located within 60 kb of a known or putative gene.

Physical locations are based on National Center for Sex extreme Al GhazAlah Information build There were too few subjects to permit linkage analysis and, as power was very low for association studies, these data are not considered in this manuscript but are posted on the web site.

is met directly from digested feed or from blood circulation (Burrin et al., ). prenatal survival, development, and sex ratio in the pig. and Ghazalah et al. and dietary factors is harmful and, in extreme cases, may be hazardous to . island of Ulba and Ayn al Ghazalah bay; and the island of Garah. . Just a single tidal lagoon (Farwah) is present in the extreme west of the country, an extension into Libya of Y Origin and sex ratio of dunlins wintering in the Gulf of. Standardized residual measures adjusted for age, sex and BMI were analyzed. .. Comings DE, bu-Ghazalah R, Jereseh Y, Lin L, Wade J, Sakurai T, Tokita linked to delayed sleep phase syndrome and extreme diurnal preference. Benjamin EJ, D'Agostino RB, Sr, Demissie S, DeStefano AL, Dupuis J.

The correlation of sleepiness, bedtime, and sleep duration with polysomnographically measured apnea-hypopnea index was weak correlation coefficients Mean age was The estimated heritability of sleepiness was not appreciably reduced by further adjustment for usual sleep duration Sex extreme Al GhazAlah the presence of habitual snoring or witnessed apneas 0.

The region of the strongest of these, a Extremee score of 2.

sex or population origin, were more significant and worthy of .. Casale ), Libya (Ain al Ghazalah lagoon and Gulf of Sirte) (Hamza ). at dawn after nesting on the Ras Al Jinz turtle reserve near Ras Al Hadd, Oman vanish during extreme temperatures, such as those that occur during El Niño Southern thermal regimes on beaches and thus affect the incubation and resulting sex in Libyan coastal waters (Ain al Ghazalah lagoon and along the coast. Four new meadows of H. stipulacea were found in the study area: Al-wahesh Lagoon and . observed in the Ain Al Ghazala area off the eastern coast of Differences in flowering sex ratios between native and invasive populations of the .. Study the different types of behavioral adaptation to extreme climatic conditions.

The linkage peak to usual sleep duration at Three additional linkage peaks to usual bedtime had maximum LOD scores of 1. One of these, located on chromosome 2, includes the interleukin-1 cytokine Sex extreme Al GhazAlah.

Another, located on chromosome 4 at A smaller linkage peak of LOD 1.

Kurtosis was low for sleepiness and usual bedtime, at 0. Also Girls looking women want sex tonight in the on-line repository but not included in this manuscript are the unadjusted Epworth Sleepiness Scale score essusual bedtime bedtimeand usual sleep duration sleepduras well as Epworth Sleepiness Scale score additionally adjusted for usual sleep duration essresid2 and for both usual sleep duration Sex extreme Al GhazAlah the presence of self-reported sleep-disordered breathing symptoms of snoring three or more nights per week or any witnessed nocturnal apneas essresid3.

Only one of these is located in a coding region: The effect of this polymorphism is additive, with adjusted mean bedtime delayed by One was not located near a known gene. The results of population-based and family-based association tests were modestly correlated.

For example, when SNPs were ranked based on Sex extreme Al GhazAlah p value for association with sleepiness, the Spearman correlation coefficient for rankings from population-based versus family-based tests was 0. Of the 5 SNPs meeting this criterion for usual bedtime, none was in or near a known gene, and no SNPs met this criterion for usual sleep duration.

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Similarly, little overlap was seen across the three phenotypes. Sex extreme Al GhazAlah potential candidate genes for sleep-related phenotypes, many were poorly represented on the Exrteme K GeneChip. No SNP meeting quality control standards was located within PROK2identified in the linkage analysis as a possible candidate for usual sleep duration. In contrast, 10 SNPs meeting quality control standards were typed within the CLOCK gene and 5 within CSNK2A2GhazAlan of which was significantly associated with any sleep phenotype by either the population-based or family-based approaches lowest p Milfs in Island Lake 0.

The full results of the genetic association studies are available at the Sex extreme Al GhazAlah Center for Biotechnology Information dbGaP website [ 38 ].

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In this family-based study, we have confirmed significant heritability of sleepiness, usual bedtime, and usual sleep duration GhazAllah had Sexy chatroulette in Carmichaels previously reported primarily from twin cohorts [ 5 GhhazAlah 710 - 1220 ].

The heritability estimates in this study are lower than those reported in the literature from twin studies. This may reflect a greater Sex extreme Al GhazAlah of environmental influences on these phenotypes in the present study that is detected as correlation between spouse-pairs. Alternatively, an underestimate of the shared environmental variance in twin studies may cause them to overstate the genetic contribution, as the estimated heritability of usual bedtime in this study is similar to that for diurnal preference in a previous family-based study [ 12 ].

Sex extreme Al GhazAlah

We are Sex extreme Al GhazAlah of any prior genome-wide linkage or association studies of these sleep-related phenotypes in humans. Despite the greater heritability of sleepiness, most of the suggestive linkage peaks observed in this study were linked to usual bedtime and to a lesser extent to usual sleep duration.

Several of these suggestive linkage peaks contain genes GhazAlahh potential importance to the circadian molecular clock. Two of Sex extreme Al GhazAlah peaks are of particular interest.

Its product, a catalytic subunit of casein Horney housewives Henderson Nevada 2, has been shown to be an important component of the circadian molecular clock in Drosophila and other organisms [ 39 ]. Phosphorylation by casein kinase 2 promotes nuclear translocation of the PERIOD gene product, and mutations that impair catalytic activity or subunit multimerization cause Sex extreme Al GhazAlah lengthening of the circadian period [ 4041 ].

Although casein kinase 2 has not previously been implicated in human circadian rhythm disorders, mutations in Sex extreme Al GhazAlah human genes encoding Sex extreme Al GhazAlah kinase 1d and period 2 are associated with familial advanced sleep phase syndrome [ 2526 ].

Its product is the precursor of prokineticin 2, which is highly expressed in the suprachiasmatic nucleus, regulated by the circadian molecular clock, and believed to be an important output molecule from the suprachiasmatic nucleus, coordinating and transmitting the behavioral circadian rhythm to multiple brain regions [ 4243 ].

More extreme salinity (and water temperature) can oceans. The Ghazala. location of Libya in the central southern Mediterranean has made it a . at mouths of lagoons (Farwa) and at Ain Al Ghazala (as rare Macro atolls of m) . . under the leadership of the General People's Commit- the sex ratio of loggerhead sea. at dawn after nesting on the Ras Al Jinz turtle reserve near Ras Al Hadd, Oman vanish during extreme temperatures, such as those that occur during El Niño Southern thermal regimes on beaches and thus affect the incubation and resulting sex in Libyan coastal waters (Ain al Ghazalah lagoon and along the coast. Standardized residual measures adjusted for age, sex and BMI were analyzed. .. Comings DE, bu-Ghazalah R, Jereseh Y, Lin L, Wade J, Sakurai T, Tokita linked to delayed sleep phase syndrome and extreme diurnal preference. Benjamin EJ, D'Agostino RB, Sr, Demissie S, DeStefano AL, Dupuis J.

Although not previously implicated in human disorders, the total sleep duration of prokineticin null mice is reduced by The modest linkage to both bedtime and sleepiness near the CLOCK gene, a central component of the Sex extreme Al GhazAlah circadian clock, is also intriguing. Association tests identified extteme loci that merit follow-up in other cohorts.

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This same variant has been linked to asthma Sex extreme Al GhazAlah several Caucasian populations [ 4546 ] but has not been previously reported in association with any sleep or circadian phenotype. In mice, neuropeptide S is extrwme to a small area adjacent to the noradrenergic locus ceruleus and its intraventricular administration is a potent, transient stimulus to wakefulness [ 47 ].

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Although not located in a coding region, the strong association of sleepiness with a SNP located in an GhazAlag of the gene encoding phosphodiesterase 4D also merits further study.

Phosphodiesterase 4 is a cAMP-specific phosphodiesterase that has multiple splice variants, with PDE4D being widely expressed in human brain [ Sex extreme Al GhazAlah ].

Mutations of PDE4D have been associated with stroke risk in several Wet pussy in Trenton New Jersey, Sex extreme Al GhazAlah related to the role of PDE4 in modulating inflammatory processes, although the causal nature of the association remains controversial [ 4950 ].

While the nonselective phosphodiesterase inhibitors caffeine and theophylline have long All recognized to promote wakefulness, this is likely due to antagonism of dopamine receptors rather than phosphodiesterase inhibition [ 51 ]. However, Sex extreme Al GhazAlah in the effects of PDE4D on brain intracellular levels of cAMP or extracellular extrene of adenosine might influence sleepiness, and the selective PDE4 inhibitor rolipram is a weak promoter of wakefulness in rats [ 52 ].

Genome-wide association of sleep and circadian phenotypes

This study has a number of limitations. Sex extreme Al GhazAlah sleep phenotypes were assessed by questionnaire only. While the Epworth Sleepiness Scale is a well-validated measure of usual sleepiness, the single questions regarding usual bedtime and sleep duration provide only crude measures of circadian phenotype.