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To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association between each single nucleotide polymorphism (SNP) and entrepreneurship. The most promising genetic variant (rs10791283 of the OPCML gene on chromosome 11q25) was significant at the 6 × 10[superscript -7] level. Suggestive associations with entrepreneurship were also identified with variants of "KIAA1199," "SYT13" and "PARD3B." Of the top 30 SNPs, 13 (43%) were located on chromosome 11, 7 (23%) on chromosome 14, and 5 (17%) on chromosome 15. However, the effect of each SNP was small, accounting for less than 1% of the variance. Our results suggest that the effects of individual common risk variants on entrepreneurship are probably very small and very large sample sizes are required to identify variants that reach genome-wide significance.

CVD is the leading cause of death worldwide and, after dementia, is the second biggest cause of death for women. In England, it accounts for one in four of all deaths. Lifestyle modifications represent the primary route both to reduce CVD risk factors and prevent CVD outcomes. Diet constitutes one of the key modifiable risk factors in the aetiology of CVD. We investigated the relationship between nine main dietary indices and a comprehensive range of CVD risk factors in 2590 women from TwinsUK. After adjustment for multiple testing, we found that the Dietary Approaches to Stop Hypertension (DASH) diet was inversely correlated with some of the most common CVD risk factors (BMI, visceral fat (VF), TAG, insulin, homoeostasis model assessment of insulin resistance (HOMA2-IR) and atherosclerotic CVD (ASCVD) risk) with PFDR ranging from 6·28 × 10−7 to 5·63 × 10−4. Similar association patterns were detected across most of the dietary indices analysed. In our post hoc investigation, to determine if any specific food groups were driving associations between the DASH score and markers of cardiometabolic risk, we found that increased BMI, VF, HOMA2-IR, ASCVD risk, insulin and TAG levels were directly correlated with red meat consumption (PFDR ranging from 4·65 × 10−9 to 7·98 × 10−3) and inversely correlated with whole-grain cereal consumption (PFDR ranging from 1·26 × 10−6 to 8·28 × 10−3). Our findings revealed that the DASH diet is associated with a more favourable CVD risk profile, suggesting that this diet may be a candidate dietary pattern to supplement current UK dietary recommendations for CVD prevention. [ABSTRACT FROM AUTHOR]

Introduction: A lack of physical activity (PA) is one of the most pressing health issues today. Our individual propensity for PA is influenced by genetic factors. Stated liking of different PA types may help capture additional and informative dimensions of PA behavior genetics. Methods: In over 157,000 individuals from the UK Biobank, we performed genome-wide association studies of five items assessing the liking of different PA types, plus an additional derived trait of overall PA-liking. We attempted to replicate significant associations in the Netherlands Twin Register (NTR) and TwinsUK. Additionally, polygenic scores (PGS) were trained in the UK Biobank for each PA-liking item and for self-reported PA behavior, and tested for association with PA in the NTR. Results: We identified a total of 19 unique significant loci across all five PA-liking items and the overall PA-liking trait, and these showed strong directional consistency in the replication cohorts. Four of these loci were previously identified for PA behavior, including CADM2 , which was associated with three PA-liking items. The PA-liking items were genetically correlated with self-reported (r g = 0.38–0.80) and accelerometer (r g = 0.26–0.49) PA measures, and with a wide range of health-related traits. Each PA-liking PGS significantly predicted the same PA-liking item in NTR. The PGS of liking for going to the gym predicted PA behavior in the NTR (r 2 = 0.40%) nearly as well as a PGS based on self-reported PA behavior (r 2 = 0.42%). Combining the two PGS into a single model increased the r 2 to 0.59%, suggesting that PA-liking captures distinct and relevant dimensions of PA behavior. Conclusions: We have identified the first loci associated with PA-liking and extended our understanding of the genetic basis of PA behavior. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diet is a modifiable risk factor for common chronic diseases and mental health disorders, and its effects are under partial genetic control. To estimate the impact of diet on individual health, most epidemiological and genetic studies have focused on individual aspects of dietary intake. However, analysing individual food groups in isolation does not capture the complexity of the whole diet pattern. Dietary indices enable a holistic estimation of diet and account for the intercorrelations between food and nutrients. In this study we performed the first ever genome-wide association study (GWA) including 173,701 individuals from the UK Biobank to identify genetic variants associated with the Dietary Approaches to Stop Hypertension (DASH) diet. DASH was calculated using the 24 h-recall questionnaire collected by UK Biobank. The GWA was performed using a linear mixed model implemented in BOLT-LMM. We identified seven independent single-nucleotide polymorphisms (SNPs) associated with DASH. Significant genetic correlations were observed between DASH and several educational traits with a significant enrichment for genes involved in the AMP-dependent protein kinase (AMPK) activation that controls the appetite by regulating the signalling in the hypothalamus. The colocalization analysis implicates genes involved in body mass index (BMI)/obesity and neuroticism ( ARPP21, RP11-62H7.2, MFHAS1, RHEBL1 ). The Mendelian randomisation analysis suggested that increased DASH score, which reflect a healthy diet style, is causal of lower glucose, and insulin levels. These findings further our knowledge of the pathways underlying the relationship between diet and health outcomes. They may have significant implications for global public health and provide future dietary recommendations for the prevention of common chronic diseases.

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting., Methods: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m 2 vs ≥30 kg/m 2 ), and comorbidities (binary variable, with or without comorbidities)., Findings: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days., Interpretation: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days., Funding: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association., Competing Interests: Declaration of interests CM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

A healthy diet is associated with the improvement or maintenance of health parameters, and several indices have been proposed to assess diet quality comprehensively. Twin studies have found that some specific foods, nutrients and food patterns have a heritable component; however, the heritability of overall dietary intake has not yet been estimated. Here, we compute heritability estimates of the nine most common dietary indices utilized in nutritional epidemiology. We analyzed 2590 female twins from TwinsUK (653 monozygotic [MZ] and 642 dizygotic [DZ] pairs) who completed a 131-item food frequency questionnaire (FFQ). Heritability estimates were computed using structural equation models (SEM) adjusting for body mass index (BMI), smoking status, Index of Multiple Deprivation (IMD), physical activity, menopausal status, energy and alcohol intake. The AE model was the best-fitting model for most of the analyzed dietary scores (seven out of nine), with heritability estimates ranging from 10.1% (95% CI [.02, .18]) for the Dietary Reference Values (DRV) to 42.7% (95% CI [.36, .49]) for the Alternative Healthy Eating Index (A-HEI). The ACE model was the best-fitting model for the Healthy Diet Indicator (HDI) and Healthy Eating Index 2010 (HEI-2010) with heritability estimates of 5.4% (95% CI [-.17, .28]) and 25.4% (95% CI [.05, .46]), respectively. Here, we find that all analyzed dietary indices have a heritable component, suggesting that there is a genetic predisposition regulating what you eat. Future studies should explore genes underlying dietary indices to further understand the genetic disposition toward diet-related health parameters.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 -8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10 -8 ) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10 -3 ) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.

Background: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber., Methods: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber intake in UK women ( n = 1810) and in a small group of UK men ( n = 64)., Results: (Poly)phenol intakes correlated with microbiome alpha diversity (Shannon Index) after adjusting for confounders and fiber intake. Moreover, flavonoid intake was significantly correlated with the abundance of Veillonella , (a genus known to improve physical performance), and stilbene intake with that of butyrate-producing bacteria ( Lachnospira and Faecalibacterium) . Stilbene and flavonoid intake also correlated with lower odds of prevalent obesity ( Stilbenes: Odds Ratio (95% Confidence Interval) (OR(95%CI)) = 0.80 (0.73, 0.87), p = 4.90 × 10 -7 ; Flavonoids : OR(95%CI) = 0.77 (0.65, 0.91), p = 0.002). Formal mediation analyses revealed that gut microbiome mediates ~11% of the total effect of flavonoid and stilbene intake on prevalent obesity., Conclusions: Our findings highlight the importance of (poly)phenol consumption for optimal human health.

TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King's College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several 'omic' technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the 'TwinsUK' resource with the scientific community - interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.

Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10 -5 ), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.

Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects.Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes.

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 -8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

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.

Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium)., Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample., Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations., Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers., Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.

Myocardial infarction (MI) is currently among the leading causes of death in the developed world. A functional SNP (rs7291467) in galectin-2 (LGALS2), a protein involved in the LTA cascade, has been associated with susceptibility to MI in the Japanese population. We explored for the first time the hypothesis that the same SNP could be associated with the risk of MI in the British population. We conducted a case-control association study on a cohort of 752 British MI patients and 705 population controls. Power calculations showed that our resource had 98% of power to detect a significant association at OR of 1.57, and 80% power to detect an association with an OR of 1.35 (recessive model). Despite this, we found no significant association of allele frequency with risk of MI. Stratification for age, gender and other cardiovascular risk factors also failed to reveal an association of this polymorphism with MI.