| 1. |
|
|
| 2. |
- Jacobs, Kevin B, et al.
(author)
-
Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
|
|
| 3. |
- Wormser, David, et al.
(author)
-
Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
-
In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
-
Journal article (peer-reviewed)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
|
|
| 4. |
- Ferrari, Raffaele, et al.
(author)
-
Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
-
In: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
-
Journal article (peer-reviewed)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
|
|
| 5. |
- Berndt, Sonja I., et al.
(author)
-
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
|
|
| 6. |
- Elks, Cathy E, et al.
(author)
-
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
-
Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
|
|
| 7. |
- Otto, Thomas D., et al.
(author)
-
A comprehensive evaluation of rodent malaria parasite genomes and gene expression
- 2014
-
In: BMC Biology. - : BioMed Central. - 1741-7007. ; 12
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Rodent malaria parasites (RMP) are used extensively as models of human malaria. Draft RMP genomes have been published for Plasmodium yoelii, P. berghei ANKA (PbA) and P. chabaudi AS (PcAS). Although availability of these genomes made a significant impact on recent malaria research, these genomes were highly fragmented and were annotated with little manual curation. The fragmented nature of the genomes has hampered genome wide analysis of Plasmodium gene regulation and function.RESULTS: We have greatly improved the genome assemblies of PbA and PcAS, newly sequenced the virulent parasite P. yoelii YM genome, sequenced additional RMP isolates/lines and have characterized genotypic diversity within RMP species. We have produced RNA-seq data and utilised it to improve gene-model prediction and to provide quantitative, genome-wide, data on gene expression. Comparison of the RMP genomes with the genome of the human malaria parasite P. falciparum and RNA-seq mapping permitted gene annotation at base-pair resolution. Full-length chromosomal annotation permitted a comprehensive classification of all subtelomeric multigene families including the 'Plasmodium interspersed repeat genes' (pir). Phylogenetic classification of the pir family, combined with pir expression patterns, indicates functional diversification within this family.CONCLUSIONS: Complete RMP genomes, RNA-seq and genotypic diversity data are excellent and important resources for gene-function and post-genomic analyses and to better interrogate Plasmodium biology. Genotypic diversity between P. chabaudi isolates makes this species an excellent parasite to study genotype-phenotype relationships. The improved classification of multigene families will enhance studies on the role of (variant) exported proteins in virulence and immune evasion/modulation.
|
|
| 8. |
- Priego, T., et al.
(author)
-
Influence of breastfeeding on blood-cell transcript-based biomarkers of health in children
- 2014
-
In: Pediatric Obesity. - : Wiley. - 2047-6310 .- 2047-6302. ; 9:6, s. 463-470
-
Journal article (peer-reviewed)abstract
- What is already known about this subject The expression of specific genes in peripheral blood cells (PBCs) may be used as biomarkers of the metabolic status. High levels of expression of CPT1A, SLC27A2, INSR, LEPR, FASN and PPAR in PBCs are indicative of a lower risk for the insulin resistant or dyslipidaemic state associated with obesity in children. Breastfeeding seems to confer protective effects against obesity and its related metabolic problems. What this study adds Children who had been breastfed showed higher expression levels of SLC27A2, FASN, PPAR and INSR in PBCs compared with formula-fed subjects. The relationship of the PBC transcript levels of SLC27A2, INSR, FASN and PPAR with insulin resistance and dyslipidaemia may be dependent on the type of infant feeding (breast vs. formula). The transcript levels of the mentioned biomarkers could be useful to distinguish the formula-fed children who are at higher risk of metabolic alterations. BackgroundBlood-cell transcripts have showed to be good biomarkers of metabolic alterations and their use in early detection and prevention of future disorders is promising. ObjectiveThis study aimed to examine the relation between previously proposed transcriptional biomarkers of metabolic health (SLC27A2, CPT1A, FASN, PPAR, INSR, LEPR) in peripheral blood cells and the type of infant feeding in a subset of children from the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort. SubjectsA total of 237 children aged 2-9 years from eight European countries were studied. ResultsBreastfed children showed higher expression levels of SLC27A2, FASN, PPAR and INSR, and lower risk of being overweight and of having high plasma triglyceride levels vs. formula-fed children. Besides, overweight formula-fed children presented higher HOMA-index than overweight breastfed children (1.90 vs. 1.62); however, this negative effect was absent in formula-fed children with high expression of SLC27A2. Moreover, formula-fed children with low expression of SLC27A2, FASN, PPAR and INSR presented higher triglyceride levels than subjects with high expression of these genes (77.7mgdL(-1) vs. 44.8mgdL(-1)). This difference was absent in breastfed children. ConclusionsProtective effects of breastfeeding are reflected in higher expression levels of SLC27A2, FASN, PPAR and INSR in blood cells. These biomarkers may also serve to discriminate the formula-fed children that are at higher risk of metabolic alterations.
|
|
| 9. |
- Svensson, A., et al.
(author)
-
European children's sugar intake on weekdays versus weekends: the IDEFICS study
- 2014
-
In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:7, s. 822-828
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To compare the intake of total sugars, foods and drinks rich in added sugar, and energy in children on weekdays (Monday Thursday), Fridays and weekends. METHODS: Dietary intake (g, kJ, energy %) was assessed using a computerized 24-h recall method in a sample of 2- to 9-year-old children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden who were participating in the IDEFICS baseline study (2007-2008). Analyses were performed in 9497 children by selecting one 24-h recall per child (for comparison of weekdays vs weekends, and Fridays vs weekdays and weekends). Selected stratified analyses were performed by country and age group. RESULTS: Intake of total sugars exceeded 20 energy % in all countries but one. In the non-stratified analyses, the intakes of total sugars and foods and drinks rich in added sugar were found to be higher on weekends compared with weekdays (both P < 0.001), and intakes on Fridays were a mix between intakes on weekdays and weekends. Energy intake did not differ between weekdays and weekends. Results were somewhat heterogeneous, both across countries and age groups. CONCLUSIONS: High intake of sugar remains an important nutritional problem in children of many European countries. Interventions aiming to prevent this diet pattern may optimize their impact by targeting dietary habits on Fridays and weekends. Furthermore, when conducting dietary assessment in children, data from weekends and Fridays in combination with a selection of Mondays to Thursdays are needed to capture habitual sugar intake. Age and dietary cultures should also be considered in dietary intervention and assessment as effect modifications were seen for both age and country.
|
|
| 10. |
|
|
