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Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

ABSTRACT: BACKGROUND:In recent years, several GWAS (genome wide association studies) of sleep-related traits have identified a number of SNPs (single nucleotides polymorphism) but their relationships with symptoms of insomnia are not known. The aim of this study was to investigate whether SNPs, previously reported in association with sleep-related phenotypes, are associated with individual symptoms of insomnia. METHODS:We selected participants from the HUNT study (Norway) who reported at least one symptom of insomnia consisting of sleep onset, maintenance or early morning awakening difficulties, (cases, N?=?2563) compared to participants who presented no symptoms at all (controls, N?=?3665). Cases were further divided in seven subgroups according to different combinations of these three symptoms. We used multinomial logistic regressions to test the association among different patterns of symptoms and 59 SNPs identified in past GWAS studies. RESULTS:Although 16 SNPS were significantly associated (p?

SUBMITTER: Bragantini D

PROVIDER: S-EPMC6852911 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

Bragantini Daniela D Sivertsen Børge B Gehrman Philip P Lydersen Stian S Güzey Ismail Cüneyt IC

BMC medical genetics 20191112 1

<h4>Background</h4>In recent years, several GWAS (genome wide association studies) of sleep-related traits have identified a number of SNPs (single nucleotides polymorphism) but their relationships with symptoms of insomnia are not known. The aim of this study was to investigate whether SNPs, previously reported in association with sleep-related phenotypes, are associated with individual symptoms of insomnia.<h4>Methods</h4>We selected participants from the HUNT study (Norway) who reported at le ...[more]

PMID: 31718593

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Project description:A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants < 0.5). In order to comprehensively evaluate variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the transcript level and may have a functional effect in cells expressing the PER3 gene. PER3 polymorphisms had a modest impact on selected sleep/circadian variables in our sample, suggesting that PER3 is associated with sleep and circadian function beyond VNTR polymorphisms. Further replicate analyses in larger, independent samples are recommended.

Project description:BackgroundAn increasing awareness exists that lack of activity engagement is associated with insomnia symptoms. However, the majority of studies have focused on the association between a single type of activity engagement and insomnia symptoms.MethodsThis is a cross-sectional study using secondary data from the Health and Retirement Study examining the relationships among different types of activity engagement and insomnia symptoms among older adults. The sample for this study included 3321 older adults who responded to survey modules on activity engagement and insomnia symptoms in 2016. Activity engagement was measured using items for three types of activities (i.e., social, cognitive, and physical) validated in this study. Insomnia symptoms were measured using four items (i.e., difficulty of falling asleep, waking up during the night, waking up too early, and feeling rested). Independent t-tests were conducted to identify the differences in insomnia symptoms according to activity engagement level. Regressions were conducted to examine the associations among three types of activity engagement and insomnia symptoms after adjusting for covariates such as demographics, chronic disease, activities of daily living difficulty, cognitive function, sleep disorder, loneliness, and caregiving.ResultsThe respondents in the high-level social, cognitive, and physical activity engagement groups were found to show fewer insomnia symptoms. Furthermore, higher social (??=?-?0.04, p?=?0.040) and cognitive (??=?-?0.06, p?=?0.007) activity engagements were associated with fewer insomnia symptoms even after adjusting for other types of activity engagement and all covariates.ConclusionsThis study suggests that older adults with higher social and cognitive activity engagements may be likely to have fewer insomnia symptoms. Based on these results, future research is needed to develop multi-component intervention programs that can encourage older adults to engage in these activities.

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Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

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Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

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