| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
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| 4. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 5. |
- Boström, Adrian Desai E., et al.
(författare)
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Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt : A cross-sectional study of suicide attempters
- 2023
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Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 160, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ability to accurately estimate risk of suicide deaths on an individual level remains elusive.Methods: This study reports on a case-control study set-up from a well-characterized cohort of 88 predominantly female suicide attempters (SA), stratified into low- (n = 57) and high-risk groups (n = 31) based on reports of later death by suicide, as well as degree of intent-to-die and lethality of SA method. We perform an unbiased analysis of 12,930 whole-blood derived CpG-sites (Illumina Infinium EPIC BeadChip) previously demonstrated to be more conciliable with brain-derived variations. The candidate site was validated by pyrosequencing. External replication was performed in (1) relation to age at index suicide attempt in 97 women with emotionally unstable personality disorder (whole-blood) and (2) death by suicide in a mixed group of 183 prefrontal-cortex (PFC) derived samples who died by suicide or from non-psychiatric etiologies.Results: CYP2D6-coupled CpG-site cg07016288 was hypomethylated in severe suicidal behavior (p < 10E-06). Results were validated by pyrosequencing (p < 0.01). Replication analyses demonstrate hypomethylation of cg07016288 in relation to age at index SA in females (p < 0.05) and hypermethylation in PFC of male suicide completers (p < 0.05). Limitations: Genotyping of CYP2D6 was not performed and CpG-site associations to gene expression were not explored.Conclusions: CYP2D6-coupled epigenetic markers are hypomethylated in females in dependency of features known to confer increased risk of suicide deaths and hypermethylated in PFC of male suicide completers. Further elucidating the role of CYP2D6 in severe suicidality or suicide deaths hold promise to deduce clinically meaningful results.
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| 6. |
- Manu, Diana-Maria
(författare)
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Functional epigenetic analyses in the context of psychiatric health in adolescence
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adolescence is a unique and formative period for learning and developing skills and abilities for adulthood. The prevalence of mental health problems in adolescents is estimated to 10-20%, being a major risk for suicide, social and academic impairments. Suicide is the third leading cause of death in older adolescents (15-19 years). Genetic studies suggest that gene-environment interaction contributes to molecular mechanisms of the differential risks for psychiatric disorders and epigenetic marks such as DNA methylation (DNAm) and non-coding RNA (ncRNA) are likely involved. In this doctoral thesis, we investigated how the environmentally modifiable factors are associated with genetic variation, anxiety disorders, depression and suicidal behavior. Using well described bioinformatic and statistical methods, e.g. DNAm preprocessing techniques, gene ontology enrichment, chromatin state inference, correlation of DNAm in blood and brain tissues and eQTL effect, we uncovered functional differential DNAm, meQTL and eQTL associations in the context of depression, generalized anxiety and suicidal thoughts in multiple datasets. First, in an epigenome-wide study, we identified associations between psychiatric-related SNPs and DNAm at CpG sites located within enhancer regions in hippocampus. Then, using a targeted approach by including CpG sites with cross tissue relevance, we found and replicated an association between differentially DNAm at one genomic locus and risk for generalized anxiety disorder. The functional role of the CpG site was supported by the observed association between DNAm shifts and mRNA expression in blood, together with its location within regulatory chromatin state in brain. In a longitudinal epigenome-wide study, we identified changes in DNAm levels at the gene promoter for risk for depression. Moreover, in blood, DNAm at one CpG site was associated with suicidal behavior and mRNA expression, which may be genetically controlled. These findings could be translated in the brain as differentially DNAm and mRNA expression levels at the same locus were observed for major depression in post-mortem tissue brain. Lastly, we identified meQTL and micro-RNA (miRNA) eQTL involved in depression in whole blood and brain. Gene ontology terms of the predicted target genes for one miRNA involved behavioral fear and defense response, presynaptic signal transductions, and presynaptic active zone organization. Overall, this thesis investigated and demonstrated a complementary influence of genetic and epigenetic factors underlying pathogenesis of psychiatric disorders.
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| 7. |
- Sokolov, Aleksandr V., et al.
(författare)
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Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
- 2023
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.
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