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Nimmons D.,University of Manchester | Pendleton N.,Salford Royal NHS Foundation Trust | Pendleton N.,University of Manchester | Payton A.,Salford Royal NHS Foundation Trust | And 6 more authors.
Neurogastroenterology and Motility | Year: 2015

Background: Catechol-O-methyl transferase (COMT) and brain-derived neurotrophic factor (BDNF) are neuro-modulatory proteins that have been demonstrated to affect cortical plasticity, which in turn has been shown to affect age-related changes and neuronal functioning in humans. Here, we tested the hypothesis that single nucleotide polymorphisms (SNP) within COMT and BDNF genes are associated with dysphagia in older adults. Methods: A total of 800 community-dwelling older individuals were sent the Sydney Oropharyngeal Dysphagia Questionnaire to identify swallowing difficulties. DNA from this population was available for study and used to genotype 18 COMT and 12 BDNF polymorphisms. Logistic regression statistical models were used to identify potential associations between dysphagia and the genotypes. Key Results: A total of 638 individuals completed the questionnaire, giving an 80% response rate. Of these, 538 were genotyped for COMT and BDNF polymorphisms. Age was found to predict dysphagia (p = 0.018, OR = 1.08, CI = 1.01-1.14). The COMT polymorphism rs165599 and the BDNF polymorphism rs10835211 were found to predict dysphagia and have an interactive effect (p = 0.028), which varied according to the carrier status of the other. In the case of SNP rs10835211, the effect of heterozygosity was protective or harmful dependent on the respective status of rs165599. Conclusions & Inferences: These results suggest that certain interactions between plasticity genes contribute to the development of dysphagia with increasing age. This highlights a possible role for genetic factors in future monitoring and treating individuals affected by dysphagia. © 2015 John Wiley & Sons Ltd. Source

Narayanan R.P.,Vascular Research Group | Payton A.,Center for Integrated Genomic Medical Research | Hudson J.E.,Vascular Research Group | Oliver R.L.,Vascular Research Group | And 7 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2013

Objective: The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration. Design: Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with real-world' longitudinal trends in body-mass index in a type 2 diabetes population. Methods: 26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort. A generalised-estimating equation (GEE) model was used to separately study the association of SNPs and IGF-II concentration with 8-year longitudinal trends in body-mass index. Results: High serum IGF-II concentration at baseline was associated with weight loss over the study period (β=-0.006, 95% CI -0.009 to -0.002, p<0.001). 8 SNPs were associated with longitudinal body-mass index trends, of which 4 retained significance after multiple testing correction. 2 SNPs rs10770063 and rs3842767 were associated with both IGF-II concentration as well as longitudinal weight changes. Conclusion: We report novel associations between polymorphisms in the IGF2 gene, with concentration of circulating IGF-II and also with longitudinal weight change in type 2 diabetes. Our data indicate that the IGF2 gene and its gene product may be important determinants of longitudinal weight trends in type 2 diabetes. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart . New York ISSN 0947-7349. Source

Quilez J.,Autonomous University of Barcelona | Short A.D.,Center for Integrated Genomic Medical Research | Martinez V.,Autonomous University of Barcelona | Kennedy L.J.,Center for Integrated Genomic Medical Research | And 4 more authors.
BMC Genomics | Year: 2011

Background: Modern dog breeds display traits that are either breed-specific or shared by a few breeds as a result of genetic bottlenecks during the breed creation process and artificial selection for breed standards. Selective sweeps in the genome result from strong selection and can be detected as a reduction or elimination of polymorphism in a given region of the genome.Results: Extended regions of homozygosity, indicative of selective sweeps, were identified in a genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at ~20,000 single-nucleotide polymorphisms (SNPs). These regions were further examined in a second dataset of Boxers collected from a different geographical location and genotyped using higher density SNP arrays (~170,000 SNPs). A selective sweep previously associated with canine brachycephaly was detected on chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26 in Boxer and for a shorter region in English and French bulldogs. It was absent in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region of extended increased heterozygosity on chromosome 9 overlapped with a previously reported copy number variant (CNV) which was polymorphic in multiple dog breeds.Conclusion: A selective sweep of more than 8 Mb on chromosome 26 was identified in the Boxer genome. This sweep is likely caused by strong artificial selection for a trait of interest and could have inadvertently led to undesired health implications for this breed. Furthermore, we provide supporting evidence for two previously described regions: a selective sweep on chromosome 1 associated with canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog breeds. © 2011 Quilez et al; licensee BioMed Central Ltd. Source

Nimmons D.,University of Manchester | Nimmons D.,Center for Integrated Genomic Medical Research | Michou E.,University of Manchester | Michou E.,Center for Integrated Genomic Medical Research | And 8 more authors.
Dysphagia | Year: 2016

Dysphagia has been estimated to affect around 8–16 % of healthy elderly individuals living in the community. The present study investigated the stability of perceived dysphagia symptoms over a 3-year period and whether such symptoms predicted death outcomes. A population of 800 and 550 elderly community-dwelling individuals were sent the Sydney Swallow Questionnaire (SSQ) in 2009 and 2012, respectively, where an arbitrary score of 180 or more was chosen to indicate symptomatic dysphagia. The telephone interview cognitive screen measured cognitive performance and the Geriatric Depression Scale measured depression. Regression models were used to investigate associations with dysphagia symptom scores, cognition, depression, age, gender and a history of stroke; a paired t test was used to examine if individual mean scores had changed. A total of 528 participants were included in the analysis. In 2009, dysphagia was associated with age (P = 0.028, OR 1.07, CI 1.01, 1.13) and stroke (P = 0.046, OR 2.04, CI 1.01, 4.11) but these associations were no longer present in 2012. Those who had symptomatic dysphagia in 2009 (n = 75) showed a shift towards improvement in swallowing (P < 0.001, mean = −174.4, CI −243.6, −105.3), and for those who died from pneumonia, there was no association between the SSQ derived swallowing score and death (P = 0.509, OR 0.10, CI −0.41, −0.20). We conclude that swallowing symptoms are a temporally dynamic process, which increases our knowledge on swallowing in the elderly. © 2016, The Author(s). Source

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