Publications
183 results found
Handley D, Rafey MF, Almansoori S, et al., 2022, Higher Waist Hip Ratio Genetic Risk Score Is Associated with Reduced Weight Loss in Patients with Severe Obesity Completing a Meal Replacement Programme, JOURNAL OF PERSONALIZED MEDICINE, Vol: 12
Pölönen J, Pinola P, Ronkainen J, et al., 2022, Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes, European Journal of Endocrinology, Vol: 187, Pages: 651-661, ISSN: 0804-4643
Objective Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular ageing. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardio-metabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population. Design Population-based cohort study: women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (PCOS) (age 31:N=190; age 46:N=207) and referent women (age 31:N=1054; age 46:N=1324) with data on LTL. Methods The association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age. Results Women with PCOS had similar mean LTL at ages 31 and 46 (P>0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P=0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P<0.001), but not in women with PCOS (P=0.96). Conclusions This finding may suggest a difference in LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.
Jiang X, Anasanti MD, Drenos F, et al., 2022, Urinary Sodium Excretion Enhances the Effect of Alcohol on Blood Pressure, HEALTHCARE, Vol: 10
Amin HA, Cordell HJ, Martin-Ruiz C, et al., 2022, No Evidence That Genetic Variation at the Klotho Locus Is Associated With Longevity in Caucasians from the Newcastle 85+Study and the UK Biobank, JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, Vol: 77, Pages: 457-461, ISSN: 1079-5006
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- Citations: 1
Cooiman M, Alsters SIM, Duquesnoy M, et al., 2022, Long-Term Weight Outcome After Bariatric Surgery in Patients with Melanocortin-4 Receptor Gene Variants: a Case-Control Study of 105 Patients, OBESITY SURGERY, Vol: 32, Pages: 837-844, ISSN: 0960-8923
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- Citations: 4
Sen P, Adewusi D, Blakemore A, et al., 2021, How do lipids influence risk of violence, self-harm and suicidality in people with psychosis? A systematic review, AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, Vol: 56, Pages: 451-488, ISSN: 0004-8674
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- Citations: 2
Zagkos L, Drenos F, Emmett P, et al., 2021, Adolescents’ dietary habits and meal patterns influence school performance in the Northern Finland Birth Cohort 1986: mendelian randomisation study
<jats:title>ABSTRACT</jats:title><jats:p>Several observational studies indicate that dietary habits in children and adolescents are associated with school performance. These associations are heavily confounded by socio-economic characteristics, such as household income and parents’ educational attainment, amongst other factors. In this study, we report observational and causal effects of habitual diet on school performance, using individual level data for 9,220 adolescents in the Northern Finland Birth Cohort 1986. For this purpose, we derived principal components for the dietary variables, meal patterns and school performance variables. The observational study showed a significant association of consumption of foods that are high in fat, salt and sugar (HFSS) with poor performance in all school subjects, and an association of consumption of healthy foods and traditional foods with good school performance in general subjects, science and physical education (PE). Moreover, a positive association was observed between not skipping breakfast and good performance in all school subjects. Mendelian randomisation analysis confirmed a negative effect of HFSS on school performance in general/science subjects (−0.080, −0.128 to −0.033) and a positive effect of healthy food on school performance in general/science subjects (0.071, 0.024 to 0.119) and PE (0.065, 0.021 to 0.110). To conclude, we identified compelling evidence that HFSS foods and healthy foods were causally affecting school performance.</jats:p>
Alkaf BA, Parkinson JP, Thomas LT, et al., 2021, Contribution of obesity and physical inactivity to the increased type 2 diabetes risk in Emiratis, Publisher: WILEY, ISSN: 0742-3071
Surendran P, Feofanova EV, Lahrouchi N, et al., 2021, Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals, Nature Genetics, Vol: 53, Pages: 1-2, ISSN: 1061-4036
Alkaf B, Blakemore A, Jarvelin M-R, et al., 2021, Secondary analyses of global datasets: do obesity and physical activity explain variation in diabetes risk across populations?, INTERNATIONAL JOURNAL OF OBESITY, Vol: 45, Pages: 944-956, ISSN: 0307-0565
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- Citations: 3
Kenkre J, Ahmed A, Purkayastha S, et al., 2021, Who will benefit from bariatric surgery for diabetes? A protocol for an observational cohort study, BMJ Open, Vol: 11, ISSN: 2044-6055
Introduction Type 2 diabetes mellitus (T2DM) and obesity are pandemic diseases that lead to a great deal of morbidity and mortality. The most effective treatment for obesity and T2DM is bariatric or metabolic surgery; it can lead to long-term diabetes remission with 4 in 10 of those undergoing surgery having normal blood glucose on no medication 1 year postoperatively. However, surgery carries risks and, additionally, due to resource limitations, there is a restricted number of patients who can access this treatment. Moreover, not all those who undertake surgery respond equally well metabolically. The objective of the current research is to prospectively investigate predictors of T2DM response following metabolic surgery, including those directly involved in its aetiopathogenesis such as fat distribution and genetic variants. This will inform development of a clinically applicable model to help prioritise this therapy to those predicted to have remission.Methods and analysis A prospective multicentre observational cohort study of adult patients with T2DM and obesity undergoing Roux-en-Y gastric bypass surgery. Patients will be comprehensively assessed before surgery to determine their clinical, metabolic, psychological, genetic and fat distribution profiles. A multivariate logistic regression model will be used to assess the value of the factors derived from the preoperative assessment in terms of prediction of diabetes remission.Ethics and dissemination Formal ethics review was undertaken with a favourable opinion (UK HRA RES reference number 18/LO/0931). The dissemination plan is to present the results at conferences, in peer-reviewed journals as well as to lay media and to patient organisations.Trial registration details ClinicalTrials.gov, Identifier: NCT03842475.
Surendran P, Gao H, Zhang W, et al., 2020, Discovery of rare variants associated with blood pressure regulation trhough meta-analaysis of 1.3 million individuals, Nature Genetics, Vol: 52, Pages: 1314-1332, ISSN: 1061-4036
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (e.g.GATA5, PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
O'Kane M, Parretti HM, Pinkney J, et al., 2020, British Obesity and Metabolic Surgery Society Guidelines on perioperative and postoperative biochemical monitoring and micronutrient replacement for patients undergoing bariatric surgery-2020 update, OBESITY REVIEWS, Vol: 21, ISSN: 1467-7881
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- Citations: 67
Pinola P, Polonen J, Ronkainen J, et al., 2020, Polycystic ovary syndrome and leukocyte telomere length: results of cross-sectional and longitudinal analyses in a birth cohort study, 36th Virtual Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 85-85, ISSN: 0268-1161
Sato MS, Kyriakopoulos M, James A, et al., 2020, Hemizygous mutations in L1CAM in two unrelated male probands with childhood onset psychosis, PSYCHIATRIC GENETICS, Vol: 30, Pages: 73-82, ISSN: 0955-8829
Li C, Stoma S, Lotta LA, et al., 2020, Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length, American Journal of Human Genetics, Vol: 106, Pages: 389-404, ISSN: 0002-9297
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Murphy J, Uttamlal T, Schmidtke KA, et al., 2020, Tracking physical activity using smart phone apps: assessing the ability of a current app and systematically collecting patient recommendations for future development, BMC Medical Informatics and Decision Making, Vol: 20, ISSN: 1472-6947
BACKGROUND: Within the United Kingdom's National Health System (NHS), patients suffering from obesity may be provided with bariatric surgery. After receiving surgery many of these patients require further support to continue to lose more weight or to maintain a healthy weight. Remotely monitoring such patients' physical activity and other health-related variables could provide healthworkers with a more 'ecologically valid' picture of these patients' behaviours to then provide more personalised support. The current study assesses the feasibility of two smartphone apps to do so. In addition, the study looks at the barriers and facilitators patients experience to using these apps effectively. METHODS: Participants with a BMI > 35 kg/m2 being considered for and who had previously undergone bariatric surgery were recruited. Participants were asked to install two mobile phone apps. The 'Moves' app automatically tracked participants' physical activity and the 'WLCompanion' app prompted participants to set goals and input other health-related information. Then, to learn about participants' facilitators and barriers to using the apps, some participants were asked to complete a survey informed by the Theoretical Domains Framework. The data were analysed using regressions and descriptive statistics. RESULTS: Of the 494 participants originally enrolled, 274 participants data were included in the analyses about their activity pre- and/or post-bariatric surgery (ages 18-65, M = 44.02, SD ± 11.29). Further analyses were performed on those 36 participants whose activity was tracked both pre- and post-surgery. Participants' activity levels pre- and post-surgery did not differ. In addition, 54 participants' survey responses suggested that the main facilitator to their continued use of the Moves app was its automatic nature, and the main barrier was its battery drain. CONCLUSIONS: The current study tracked physical activity in patien
Amin HA, Drenos F, Blakemore AI, 2019, Variation at the Klotho gene locus does not affect cognitive function in up to 335,074 British Caucasians in the UK Biobank
<jats:title>Abstract</jats:title><jats:p>The proportion of older adults in Western populations is increasing and there is, therefore, a need to define factors affecting maintenance of physical and cognitive health in old age. Variations in the Klotho (<jats:italic>KL</jats:italic>) gene, and specifically the <jats:italic>KL</jats:italic>-VS haplotype, have been identified by several authors as potentially influencing cognitive function and decline. We have attempted to verify the reported associations between <jats:italic>KL</jats:italic> variants, including the <jats:italic>KL</jats:italic>-VS haplotype, and cognitive function in up to 335,074 British Caucasian participants aged 40-79 years from the UK Biobank. We do not find evidence that <jats:italic>KL</jats:italic>-VS affects cognitive function or its decline with increasing age. We examined a further 244 <jats:italic>KL</jats:italic> variants and found that rs117650866 was associated with Prospective Memory, but could not replicate this in follow-up samples. In conclusion, there is insufficient evidence in the UK Biobank to support the concept that <jats:italic>KL</jats:italic> variants affect cognitive function or its rate of decline.</jats:p>
Wilson MSJ, Knight S, Vaughan-Shaw P, et al., 2019, A modified AUGIS Delphi process to establish research priorities in bariatric and metabolic surgery, CLINICAL OBESITY, Vol: 10, ISSN: 1758-8103
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- Citations: 6
Cooiman MI, Kleinendorst L, Aarts EO, et al., 2019, Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity, OBESITY SURGERY, Vol: 30, Pages: 470-477, ISSN: 0960-8923
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- Citations: 29
Almansoori S, Alsters SI, Chahal HS, et al., 2019, Analysis of genes associated with obesity phenotypes in mouse models, reveals new potentially causative mutations for monogenic obesity in humans, 52nd Conference of the European-Society-of-Human-Genetics (ESHG), Publisher: NATURE PUBLISHING GROUP, Pages: 1838-1838, ISSN: 1018-4813
Yiorkas AM, Leinhard O, Blakemore AI, 2019, Population-based assessment of the phenotypic profile of Melanocortin-4 Receptor mutation carriers, 52nd Conference of the European-Society-of-Human-Genetics (ESHG), Publisher: NATURE PUBLISHING GROUP, Pages: 1763-1764, ISSN: 1018-4813
Alves AC, De Silva NMG, Karhunen V, et al., 2019, GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI, Science Advances, Vol: 5, ISSN: 2375-2548
Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here we combine genome-wide association studies with modelling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score and co-localization analyses to determine how developmental timings, molecular pathways and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult BMI, with variants associated with adult BMI acting as early as 4-6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Evangelou E, Gao H, Blakeley P, et al., 2019, New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders, Nature Human Behaviour, Vol: 3, Pages: 950-961, ISSN: 2397-3374
Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d−1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.
Kidd ED, Walley A, Buxton J, et al., 2019, Impact of diet, household income and stress on telomere length in a cohort of Colombian schoolchildren, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 1022-1023, ISSN: 1018-4813
Fairbrother U, Kidd E, Buxton J, et al., 2019, Blood glucose, BMI and telomere length in a cohort of Colombian schoolchildren, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 1038-1039, ISSN: 1018-4813
Szepietowski O, Alsters S, Mahir G, et al., 2019, Recent-Onset Type 2 Diabetes Is Defined As < 10 Years Duration, 10th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S11-S11, ISSN: 0960-8923
Ji Y, Yiorkas AM, Frau F, et al., 2019, Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension, Diabetes, Vol: 68, Pages: 207-219, ISSN: 0012-1797
Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.
De Silva M, Sebert S, Alves AC, et al., 2018, Genetic architecture of early growth phenotypes gives insights into their link with later obesity, Publisher: NATURE PUBLISHING GROUP
Macare C, Ducci F, Zhang Y, et al., 2018, A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response, European Neuropsychopharmacology, Vol: 28, Pages: 1103-1114, ISSN: 0924-977X
The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.
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