Biology subjects

Kristiansson, K.

Publications and source records attributed to Kristiansson, K..

3 recordsLinked to original sources

bioRxiv2019

Nightmares share strong genetic risk with sleep and psychiatric disorders

Nightmares are vivid, extended and extremely dysphoric dreams that awaken the dreamer. Twin studies indicate that nightmare frequency has a heritability between 36 and 51% providing evidence for genetic factors underlying predisposition to nightmares. Furthermore, while cross-sectional epidemiological findings suggest that heavy alcohol usage, traumatic experiences and psychiatric diseases associate with nightmares, the causal relationships between these conditions and nightmares have remained unknown. To examine the biological mechanisms behind nightmares, we performed a genome-wide association study in 28,596 individuals from Finland and the United States. We identified individual genetic variants that predispose to nightmares near MYOF (rs701873, p=2.18e-8) and PTPRJ (rs11039471,p=3.7e-8), a gene previously associated with sleep duration. We found a strong genetic correlation between the frequency of nightmares and traits related to personality and psychiatric disorders; neuroticism (rg=0.59, p=8e-7), post-traumatic stress disorder (PTSD) (rg=0.58, p=0.004) as well as major depressive disorder (rg=0.68, p=7e-4), and sleep traits; and daytime sleepiness (rg=0.62, p=1e-6) and insomnia (rg=0.50, p=1.87e-5). Analysis of directionality using mendelian randomization showed a significant effect from feelings of fed-up (p=0.001), nervous (p=0.004) and miserableness (p=0.0045) to nightmares with no evidence of pleiotropy and no evidence of nightmares predisposing to psychiatric or psychological problems. Our findings suggest that nightmares are caused by unique genetic risk factors, and here we identify the first individual genetic associations. In addition, a substantial effect on nightmares is conveyed through underlying psychological and sleep problems, with psychological problems being causal for nightmares.

genetics↗

bioRxiv2019

Genetic variation in apolipoprotein A-I concentrations and risk of coronary artery disease

RationaleApolipoprotein A-I (apoA-I) infusions represent a potential novel therapeutic approach for the prevention of coronary artery disease (CAD) with phase III cardiovascular outcome trials currently underway. Although circulating apoA-I levels inversely associate with risk of CAD, the evidence base of this representing a causal relationship is lacking.\n\nObjectiveTo assess the causal role of apoA-I in CAD using human genetics.\n\nMethods and ResultsWe identified a variant (rs12225230) in APOA1 locus that associated with circulating apoA-I concentrations at GWAS significance (P<5x10-8) in 20,370 Finnish participants and meta-analyzed our data with a previous genome-wide association study of apoA-I. We obtained genetic estimates of CAD from UK Biobank and CARDIoGRAMplusC4D (totaling 122,733 CAD cases) and conducted a two-sample Mendelian randomization analysis. We compared our genetic findings to observational associations of apoA-I with risk of CAD in 918 incident CAD cases among 11,535 individuals from population-based prospective cohorts. We also summarized the available evidence from randomized controlled trials (RCTs) of apoA-I infusion therapies reporting CAD events. ApoA-I was associated with a lower risk of CAD in observational analyses (HR 0.81; 95%CI: 0.75, 0.88; per 1-SD higher apoA-I), with the association showing a dose-response relationship. Rs12225230 associated with apoA-I concentrations (per-C allele beta 0.076 SD; SE: 0.013; P=1.5x10-9) but not with potential confounders. In Mendelian randomization analyses, apoA-I was not related to risk of CAD (OR 1.13; 95%CI: 0.98, 1.30 per 1-SD higher apoA-I), which was different to the observational association (P-het<0.001). RCTs of apoA-I infusions did not show an effect on the risk of CAD.\n\nConclusionsGenetic evidence fails to support a cardioprotective role for apoA-I. This casts doubt on the likely benefit of apoA-I infusion therapy in the ongoing phase III cardiovascular outcome trial.

epidemiology↗

bioRxiv2018

Genome-wide association analysis of excessive daytime sleepiness identifies 42 loci that suggest phenotypic subgroups

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. We identified 42 loci for self-reported EDS in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirmed the aggregate effect of a genetic risk score of 42 SNPs on EDS in independent Scandinavian cohorts and on other sleep disorders (restless leg syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). Strong genetic correlations were also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing. EDS variants clustered into two predominant composite phenotypes - sleep propensity and sleep fragmentation - with the former showing stronger evidence for enriched expression in central nervous system tissues, suggesting two unique mechanistic pathways. Mendelian randomization analysis indicated that higher BMI is causally associated with EDS risk, but EDS does not appear to causally influence BMI.

genomics↗