| 1. |
- Artigas Soler, María, et al.
(författare)
-
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
|
|
| 2. |
- Wain, Louise V, et al.
(författare)
-
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
|
|
| 3. |
- Vogelezang, Suzanne, et al.
(författare)
-
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Mishra, Gita D., et al.
(författare)
-
MatCH (Mothers and their Children's Health) Profile : Offspring of the 1973-78 Cohort of the Australian Longitudinal Study on Women's Health
- 2018
-
Ingår i: Longitudinal and Life Course Studies. - : Bristol University Press. - 1757-9597. ; 9:3, s. 351-375
-
Tidskriftsartikel (refereegranskat)abstract
- MatCH (Mothers and their Children's Health) is a nationwide Australian study to investigate the links between the history of health, wellbeing and living conditions of mothers and the health and development of their children. MatCH builds on the Australian Longitudinal Study on Women's Health (ALSWH), which began in 1996 and has surveyed more than 58,000 women in four nationally representative age cohorts. MatCH focuses on the three youngest offspring of the cohort of ALSWH participants randomly sampled from all women in Australia born in 1973-78 (N=5780 children of N=3039 mothers). These women, who had completed up to seven postal or online surveys since 1996, were invited in 2016-17 to complete surveys about the health and development of their three youngest children aged under 13. The mothers reported on their children's health conditions and symptoms, diet, anthropometric measures, childcare, screen time, physical activity, temperament, behaviour, language development, motor development and health service utilisation, as well as household and environmental factors. These data are being linked with each child's records from official sources including the Australian Early Development Census (collected at age five to six), the National Assessment Program-Literacy and Numeracy (collected at age eight, 10, 12 and 14) and other external datasets. MatCH will combine 20 years of maternal data with all the information on her children, taking into account the family setting. MatCH offers an unprecedented opportunity to advance our understanding of the relationship between maternal health and wellbeing and child health and development.
|
|
| 7. |
- Parvez, Sarker Masud, et al.
(författare)
-
Hormonal, liver, and renal function associated with electronic waste (e-waste) exposure in Dhaka, Bangladesh
- 2024
-
Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 505
-
Tidskriftsartikel (refereegranskat)abstract
- Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63 mu g/dL), similar blood cadmium (Cd) (1.04 vs 0.99 mu g/L) and lower total mercury (Hg) in hair (0.38 vs 0.57 ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT3), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p <= 0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p >= 0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.002, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p >= 0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from ewaste exposure.
|
|
| 8. |
- Chen, Yiqin, et al.
(författare)
-
Monthly variation in faeces : blood concentration ratio of persistent organic pollutants over the first year of life
- 2016
-
Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 147, s. 259-268
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies have found that the concentrations of a range of persistent organic pollutants (POPs) in faeces is linearly proportional to the POP concentrations in blood of human adults irrespective of age and gender. In order to investigate the correlation between POP concentrations in faeces and blood in infants, the monthly variation of POP concentrations in faeces over the first year of life of one infant was investigated in this study and compared to modelled blood concentrations. Faecal samples were collected from one male infant daily. The samples were pooled by month and analysed for three selected POPs (2,2',4,4',5,5'-Hexachlorobiphenyl (PCB153), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and 2,2',4,4'-tetrabromodiphenyl ether (BDE47)). The POP concentrations in faecal samples increased for the first four months by a factor of 2.9, 4.9 and 1.4 for PCB153, BDE47, and p,p'-DDE, respectively. The faecal concentrations of all POPs decreased rapidly following the introduction of formula and solid food to the diet and subsequent weaning of the infant. Further, a one-compartment model was developed to estimate the daily POP concentrations in the blood of the infant. The POP concentrations in blood were predicted to vary much less over the first year than those observed in faeces. The faeces:blood concentration ratio of selected POPs (K-fb) differed significantly (P < 0.0001) between the period before and after weaning, and observed changes in K-fb are far greater than the uncertainty in the estimated K-fb. A more stable K-fb after weaning indicates the possibility of applying the stable K-fb values for non-invasive assessment of internal exposure in infants after weaning. The intra-individual variation in K-fb in infants is worthy of further investigation.
|
|
| 9. |
- Chen, Yiqin, et al.
(författare)
-
Persistent organic pollutants in infants and toddlers : Relationship between concentrations in matched plasma and faecal samples
- 2017
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 82-88
-
Tidskriftsartikel (refereegranskat)abstract
- Early-childhood biomonitoring of persistent organic pollutants (POPs) is challenging due to the logistic and ethical limitations associated with blood sampling. We investigated using faeces as a non-invasive matrix to estimate internal exposure to POPs. The concentrations of selected POPs were measured in matched plasma and faecal samples collected from 20 infants/toddlers (aged 13 +/- 4.8 months), including a repeat sample time point for 13 infants (similar to 5 months apart). We observed higher rates of POP quantification in faeces (2 g dry weight) than in plasma (0.5 mL). Among the five chemicals that had quantification frequencies over 50% in both matrices, except for HCB, log concentration in faeces (C-f) and blood (C-b) were correlated (r > 0.74, P < 0.05) for p.p'-dichlorodiphenyldichloroethylene (p,p'-DDE), 2,3', 4,4', 5-pentachlorobiphenyl (PCB118), 2,2', 3,4,4', 5'-pentachlorobiphenyl (PCB138) and 2,2', 4,4', 5,5'-pentachlorobiphenyl (PCB153). We determined faeces: plasma concentration ratios (K-fb), which can be used to estimate C-b from measurements of C-f for infants/toddlers. For a given chemical, the variation in K-fb across individuals was considerable (CV from 0.46 to 0.70). Between 5% and 50% of this variation was attributed to short-term intra-individual variability between successive faecal samples. This variability could be reduced by pooling faeces samples over several days. Some of the remaining variability was attributed to longer-term intra-individual variability, which was consistent with previously reported observations of a decrease in K-fb over the first year of life. The strong correlations between C-f and C-b demonstrate the promise of using faeces for biomonitoring of these compounds. Future research on the sources of variability in K-fb could improve the precision and utility of this technique.
|
|
| 10. |
- Chen, Yiqin, et al.
(författare)
-
Persistent organic pollutants in matched breast milk and infant faeces samples
- 2015
-
Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 118, s. 309-314
-
Tidskriftsartikel (refereegranskat)abstract
- Assessing blood concentration of persistent organic pollutants (POPs) in infants is difficult due to the ethical and practical difficulties in obtaining sufficient quantities of blood. To determine whether measuring POPs in faeces might reflect blood concentration during infancy, we measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal samples obtained from ten mother-child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal sampling. In this small dataset faecal concentrations (range 0.01-41 ng g(-1) lipid) are strongly associated with milk concentrations (range 0.02-230 ng g(-1) lipid). Associations with other factors generally could not be detected in this dataset, with the exception of a small effect of age or growth. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-individual variability in the faeces-to-milk concentration ratio R-fm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.
|
|
