| 1. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)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.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)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. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 5. |
- Sen, Partha, et al.
(author)
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Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
- 2013
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In: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 34:6, s. 801-811
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Journal article (peer-reviewed)abstract
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
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| 6. |
- Beecham, Ashley H, et al.
(author)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Journal article (peer-reviewed)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 7. |
- Cook, Michael J., et al.
(author)
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Frailty and bone health in European men
- 2017
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In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 46:4, s. 635-641
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Journal article (peer-reviewed)abstract
- Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health.Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre.Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05).Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.
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| 8. |
- Tyekucheva, Svitlana, et al.
(author)
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Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
- 2017
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In: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.Stromal cells contribute to tumor development but the mechanisms regulating this process are still unclear. Here the authors analyze gene expression profiles in the prostate and show that stromal gene signature changes ahead of the epithelial gene signature as prostate cancer initiates and progresses.
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| 9. |
- Ahern, Tomás, et al.
(author)
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Natural history, risk factors and clinical features of primary hypogonadism in ageing men : Longitudinal Data from the European Male Ageing Study
- 2016
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In: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 85:6, s. 891-901
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Journal article (peer-reviewed)abstract
- Objective: In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone (LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism (PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men. Design, Patients and Measurements: A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years. Men were classified as incident (i) PHG (eugonadal [EUG, T ≥ 10·5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG (PHG at baseline and follow-up), pEUG (EUG at baseline and follow-up) and reversed (r) PHG (PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models. Results: Of 1,991 men comprising the analytical sample, 97·5% had pEUG, 1·1% iPHG, 1·1% pPHG and 0·3% rPHG. The incidence of PHG was 0·2%/year. Higher age (>70 years) [OR 12·48 (1·27-122·13), P = 0·030] and chronic illnesses [OR 4·24 (1·08-16·56); P = 0·038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance. Conclusions: Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study.
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| 10. |
- Antonio, Leen, et al.
(author)
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Associations Between Sex Steroids and the Development of Metabolic Syndrome: A Longitudinal Study in European Men
- 2015
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1396-1404
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Journal article (peer-reviewed)abstract
- Context: Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol (E2) may also be associated with MetS, but few studies have investigated this. Objective: To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk. Methods: Three thousand three hundred sixty nine community-dwelling men aged 40-79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS. Results: One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS [odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P < .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001). Conclusions: Inmen, lower Tlevels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
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