| 1. |
- Djureinovic, Tatjana, et al.
(författare)
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The CHEK2 1100delC variant in Swedish colorectal cancer
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
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| 2. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 3. |
- Angenete, Eva, 1972, et al.
(författare)
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Laparoscopic Lavage Is Feasible and Safe for the Treatment of Perforated Diverticulitis With Purulent Peritonitis The First Results From the Randomized Controlled Trial DILALA
- 2016
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 263:1, s. 117-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To evaluate short-term outcomes of a new treatment for perforated diverticulitis with purulent peritonitis in a randomized controlled trial.Background:Perforated diverticulitis with purulent peritonitis (Hinchey III) has traditionally been treated with surgery including colon resection and stoma (Hartmann procedure) with considerable postoperative morbidity and mortality. Laparoscopic lavage has been suggested as a less invasive surgical treatment.Methods:Laparoscopic lavage was compared with colon resection and stoma in a randomized controlled multicenter trial, DILALA (ISRCTN82208287). Initial diagnostic laparoscopy showing Hinchey III was followed by randomization. Clinical data was collected up to 12 weeks postoperatively.Results: Eighty-three patients were randomized, out of whom 39 patients in laparoscopic lavage and 36 patients in the Hartmann procedure groups were available for analysis. Morbidity and mortality after laparoscopic lavage did not differ when compared with the Hartmann procedure. Laparoscopic lavage resulted in shorter operating time, shorter time in the recovery unit, and shorter hospital stay.Conclusions:In this trial, laparoscopic lavage as treatment for patients with perforated diverticulitis Hinchey III was feasible and safe in the short-term.
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| 4. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 5. |
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| 6. |
- Bustamante, Mariona, et al.
(författare)
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A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:18, s. 4127-4142
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Tidskriftsartikel (refereegranskat)abstract
- More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N=5758) followed by replication (N=3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
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| 7. |
- Christensen, Emil Dalgaard, et al.
(författare)
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The developing airway and gut microbiota in early life is influenced by age of older siblings
- 2022
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Ingår i: Microbiome. - : BioMed Central (BMC). - 2049-2618. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Growing up with siblings has been linked to numerous health outcomes and is also an important determinant for the developing microbiota. Nonetheless, research into the role of having siblings on the developing microbiota has mainly been incidental.Results: Here, we investigate the specific effects of having siblings on the developing airway and gut microbiota using a total of 4497 hypopharyngeal and fecal samples taken from 686 children in the COPSAC2010 cohort, starting at 1 week of age and continuing until 6 years of age. Sibship was evaluated longitudinally and used for stratification. Microbiota composition was assessed using 16S rRNA gene amplicon sequencing of the variable V4 region. We found siblings in the home to be one of the most important determinants of the developing microbiota in both the airway and gut, with significant differences in alpha diversity, beta diversity, and relative abundances of the most abundant taxa, with the specific associations being particularly apparent during the first year of life. The age gap to the closest older sibling was more important than the number of older siblings. The signature of having siblings in the gut microbiota at 1 year was associated with protection against asthma at 6 years of age, while no associations were found for allergy.Conclusions: Having siblings is one of the most important factors influencing a child's developing microbiota, and the specific effects may explain previously established associations between siblings and asthma and infectious diseases. As such, siblings should be considered in all studies involving the developing microbiota, with emphasis on the age gap to the closest older sibling rather than the number of siblings. Video abstract.
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| 8. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 9. |
- Gupta, Shashank, 1989-, et al.
(författare)
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Amplicon sequencing provides more accurate microbiome information in healthy children compared to culturing
- 2019
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Next-Generation Sequencing (NGS) of 16S rRNA gene is now one of the most widely used application to investigate the microbiota at any given body site in research. Since NGS is more sensitive than traditional culture methods (TCMs), many studies have argued for them to replace TCMs. However, are we really ready for this transition? Here we compare the diagnostic efficiency of the two methods using a large number of samples (n = 1,748 fecal and n = 1,790 hypopharyngeal), among healthy children at different time points. Here we show that bacteria identified by NGS represented 75.70% of the unique bacterial species cultured in each sample, while TCM only identified 23.86% of the bacterial species found by amplicon sequencing. We discuss the pros and cons of both methods and provide perspective on how NGS can be implemented effectively in clinical settings.
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| 10. |
- Gupta, Shashank, 1989-, et al.
(författare)
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Environmental shaping of the bacterial and fungal community in infant bed dust and correlations with the airway microbiota
- 2020
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Ingår i: Microbiome. - : BioMed Central (BMC). - 2049-2618. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: From early life, children are exposed to a multitude of environmental exposures, which may be of crucial importance for healthy development. Here, the environmental microbiota may be of particular interest as it represents the interface between environmental factors and the child. As infants in modern societies spend a considerable amount of time indoors, we hypothesize that the indoor bed dust microbiota might be an important factor for the child and for the early colonization of the airway microbiome. To explore this hypothesis, we analyzed the influence of environmental exposures on 577 dust samples from the beds of infants together with 542 airway samples from the Copenhagen Prospective Studies on Asthma in Childhood2010 cohort.Results: Both bacterial and fungal community was profiled from the bed dust. Bacterial and fungal diversity in the bed dust was positively correlated with each other. Bacterial bed dust microbiota was influenced by multiple environmental factors, such as type of home (house or apartment), living environment (rural or urban), sex of siblings, and presence of pets (cat and/or dog), whereas fungal bed dust microbiota was majorly influenced by the type of home (house or apartment) and sampling season. We further observed minor correlation between bed dust and airway microbiota compositions among infants. We also analyzed the transfer of microbiota from bed dust to the airway, but we did not find evidence of transfer of individual taxa.Conclusions: Current study explores the influence of environmental factors on bed dust microbiota (both bacterial and fungal) and its correlation with airway microbiota (bacterial) in early life using high-throughput sequencing. Our findings demonstrate that bed dust microbiota is influenced by multiple environmental exposures and could represent an interface between environment and child.
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