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Endothelin-1 (EDN1) has been reported to be implicated in the pathophysiology of asthma. Literature results on the genetic association of EDN1 in asthma are inconsistent. Eleven single nucleotide polymorphisms in EDN1 were genotyped in 342 and 100 families from UK and Norway, respectively. Asthma, bronchial hyperreactivity (BHR) and atopic asthma phenotypes were analyzed for the family-based association. Five single nucleotide polymorphisms (SNPs) were associated with asthma (0.0017P0.0291), five with BHR (0.0026P0.0315) and three with atopic asthma (0.0016P0.041) in the UK population. Three SNPs were associated with asthma (0.0041P0.019), seven with BHR (0.0018P0.041) and two with atopic asthma (0.0123P0.0153) in the Norwegian population. A polymorphism (rs1800541) in the promoter region of EDN1 was replicated in the two populations. A nonsynonymous coding polymorphism (rs5370) resulting in a change of amino acid Asn to Lys at position 198 was also replicated. The results of haplotype-based association analyses strongly supported the ones of single SNP associations. This study demonstrates the significant evidence of association between polymorphisms in EDN1 and asthma.Genes and Immunity (2008) 9, 23–29; doi:10.1038/sj.gene.6364441; published online 25 October 2007 [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cause of cancer death in UK men. We have shown a higher incidence and disease stage in black British men (unpublished), however there is no evidence regarding their awareness of prostate cancer and screening. We assessed the level of prostate cancer awareness and attitudes in Black and White men in the UK, and to see if written information would modify awareness. Information was collected from two groups of 871 men without prostate cancer using a new, validated, prostate cancer awareness questionnaire. The first group was asked to fill in the questionnaire, whereas the second group was initially given printed information on prostate cancer and requested to fill in the questionnaire. Data were compared between the two ethnic groups using SPSS statistical package. Changes in knowledge and attitudes after providing prostate health education were analysed. There was a significantly lower response from Black men. In the first group, Black men were unaware of their increased risk of developing the disease and demonstrated poor knowledge about the symptoms of prostate cancer (P<0.001) and also more negative attitudes about its control and treatment (P<0.01). In the second group, there were significant improvements in knowledge, risk awareness and attitudes following targeted education: this was true for Black and White men. Although Black British men have a high risk of prostate cancer, their knowledge of the disease is poor. Simple education methods can significantly improve awareness and knowledge in both Black and White men.Prostate Cancer and Prostatic Diseases (2007) 10, 256–260; doi:10.1038/sj.pcan.4500961; published online 20 March 2007 [ABSTRACT FROM AUTHOR]

The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively. Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (−731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses supported the ones of the single SNP analyses. Thus, we demonstrated significant evidence of association between polymorphisms in PTGDR with asthma phenotypes in the two Caucasian populations.Genes and Immunity (2007) 8, 398–403; doi:10.1038/sj.gene.6364399; published online 31 May 2007 [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identify 143 independent loci in 112 1-Mb regions, providing insights into the physiology of vitamin D and implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Mendelian randomization models find no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.

Study Objectives: Normal timing and duration of sleep is vital for all physical and mental health. However, many sleep-related studies depend on self-reported sleep measurements, which have limitations. This study aims to investigate the association of physical activity and sociodemographic characteristics including age, gender, coffee intake and social status with objective sleep measurements., Methods: A cross-sectional analysis was carried out on 82995 participants within the UK Biobank cohort. Sociodemographic and lifestyle information were collected through touch-screen questionnaires in 2007-2010. Sleep and physical activity parameters were later measured objectively using wrist-worn accelerometers in 2013-2015 (participants were aged 43-79 years and wore watches for 7 days). Participants were divided into 5 groups based on their objective sleep duration per night (<5 hours, 5-6 hours, 6-7 hours, 7-8 hours and >8 hours). Binary logistic models were adjusted for age, gender and Townsend Deprivation Index., Results: Participants who slept 6-7 hours/night were the most frequent (33.5%). Females had longer objective sleep duration than males. Short objective sleep duration (<6 hours) correlated with older age, social deprivation and high coffee intake. Finally, those who slept 6-7 hours/night were most physically active., Conclusions: Objectively determined short sleep duration was associated with male gender, older age, low social status and high coffee intake. An inverse 'U-shaped' relationship between sleep duration and physical activity was also established. Optimal sleep duration for health in those over 60 may therefore be shorter than younger groups., Competing Interests: The authors have declared that no competing interests exist.

The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.

In the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genome-wide significant evidence for chromosome 20q11.22 harboring the ASIP gene being explicitly associated with skin color in Europeans. In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4), 15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin coloration in Europeans. In follow-up gene expression and regulation studies of 22 genes in 20q11.22, we highlighted two novel genes EIF2S2 and GSS, serving as competing functional candidates in this region and providing future research lines. A genetically inferred skin color score obtained from the 9 top-associated SNPs from 9 genes in 940 worldwide samples (HGDP-CEPH) showed a clear gradual pattern in Western Eurasians similar to the distribution of physical skin color, suggesting the used 9 SNPs as suitable markers for DNA prediction of skin color in Europeans and neighboring populations, relevant in future forensic and anthropological investigations.

Context: Age at menarche (AAM) is an important trait both biologically and socially, a clearly defined event in female pubertal development, and has been associated with many clinically significant phenotypes., Objective: The objective of the study was to identify genetic loci influencing variation in AAM in large population-based samples from three countries., Design/participants: Recalled AAM data were collected from 13,697 individuals and 4,899 pseudoindependent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components linkage analysis was implemented on each sample individually and in combination., Results: The mean, sd, and heritability of AAM across the three samples was 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined analysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds = 2.0). Three loci of suggestive significance were seen in the U.K. sample on chromosomes 1, 4, and 18 (logarithm of the odds = 2.4, 2.2 and 3.2, respectively)., Conclusions: There was no evidence for common highly penetrant variants influencing AAM. Linkage and association suggest that one trait locus for AAM is located on chromosome 12, but further studies are required to replicate these results.