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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Ayoola, A, et al.
(författare)
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Overweight and obesity in south central Uganda: A population-based study
- 2022
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Ingår i: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:11, s. e0001051-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a rapidly growing global health challenge, but there are few population-level studies from non-urban settings in sub-Saharan Africa. We evaluated the prevalence of overweight (body mass index (BMI)>25 kg/m2), obesity (BMI>30 kg/m2), and associated factors using data from May 2018 to November 2020 from the Rakai Community Cohort Study, a population-based cohort of residents aged 15 to 49 living in forty-one fishing, trading, and agrarian communities in South Central Uganda. Modified Poisson regression was used to estimate adjusted prevalence risk ratios (PRR) and 95% confidence intervals (CI) in 18,079 participants. The overall mean BMI was 22.9 kg/m2. Mean BMI was 21.5 kg/m2 and 24.1 kg/m2 for males and females, respectively. The prevalence of overweight and obesity were 22.8% and 6.2%, respectively. Females had a higher probability of overweight/obesity (PRR: 4.11, CI: 2.98–5.68) than males. For female participants, increasing age, higher socioeconomic status, residing in a trading or fishing community (PRR: 1.25, CI 1.16–1.35 and PRR: 1.17, CI 1.10–1.25, respectively), being currently or previously married (PRR: 1.22, CI 1.07–1.40 and PRR: 1.16, CI 1.01–1.34, respectively), working in a bar/restaurant (PRR: 1.29, CI 1.17–1.45), trading/shopkeeping (PRR: 1.38, CI 1.29–1.48), and reporting alcohol use in the last year (PRR: 1.21, CI 1.10–1.33) were risk factors for overweight/obese. For male participants, increasing age, higher socioeconomic status, being currently married (PRR: 1.94, CI 1.50–2.50), residing in a fishing community (PRR: 1.68, CI 1.40–2.02), working in a bar/restaurant (PRR: 2.20, CI 1.10–4.40), trading/shopkeeping (PRR: 1.75, CI 1.45–2.11), or fishing (PRR: 1.32, CI 1.03–1.69) increased the probability of overweight/obesity. Non-Muslim participants, male smokers, and HIV-positive females had a lower probability of overweight/obese. The prevalence of overweight/obesity in non-urban Ugandans is substantial. Targeted interventions to high-risk subgroups in this population are needed.
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- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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