Publications
368 results found
Deloukas P, Kanoni S, Willenborg C, et al., 2013, Large-scale association analysis identifies new risk loci for coronary artery disease, NATURE GENETICS, Vol: 45, Pages: 25-U52, ISSN: 1061-4036
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- Citations: 959
Mills RK, Tan ST, Loh M, et al., 2013, DOES INACCURATE DEATH CERTIFICATION CONTRIBUTE TO THE REPORTED HIGH RISK OF CARDIOVASCULAR DISEASE AMONGST INDIAN ASIANS?, CARDIOLOGY, Vol: 126, Pages: 154-154, ISSN: 0008-6312
Mielewczik M, Cole GD, Nowbar AN, et al., 2013, The C-CURE Randomized Clinical Trial (Cardiopoietic stem Cell therapy in heart failURE), Journal of the American College of Cardiology, Vol: 62, Pages: 2453-2453
van der Harst P, Zhang W, Leach IM, et al., 2012, Seventy-five genetic loci influencing the human red blood cell, NATURE, Vol: 492, Pages: 369-+, ISSN: 0028-0836
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- Citations: 242
Huang J, Sabater-Lleal M, Asselbergs FW, et al., 2012, Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation, BLOOD, Vol: 120, Pages: 4873-4881, ISSN: 0006-4971
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- Citations: 72
Chahal NS, Lim TK, Jain P, et al., 2012, Population-Based Reference Values for 3D Echocardiographic LV Volumes and Ejection Fraction, JACC-CARDIOVASCULAR IMAGING, Vol: 5, Pages: 1191-1197, ISSN: 1936-878X
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- Citations: 68
Chaturvedi N, Bathula R, Shore AC, et al., 2012, South Asians have elevated postexercise blood pressure and myocardial oxygen consumption compared to Europeans despite equivalent resting pressure, Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease, Vol: 1, Pages: 1-9, ISSN: 2047-9980
BackgroundStroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this.Methods and ResultsA population‐based sample of 147 European and 145 South Asian middle‐aged men and women performed the Dundee 3‐minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate–pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, −0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate–pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, −39 to 561 mm Hg/min; P=0.3]).ConclusionPostexercise recovery of BP and rate–pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians.
Okada Y, Sim X, Go MJ, et al., 2012, Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations, NATURE GENETICS, Vol: 44, Pages: 904-+, ISSN: 1061-4036
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- Citations: 220
Chahal NS, Lim TK, Jain P, et al., 2012, Brain natriuretic peptide is independently associated with indices of left ventricular filling pressure but not with left ventricular mass in asymptomatic individuals, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 726-726, ISSN: 0195-668X
Braun TR, Been LF, Singhal A, et al., 2012, A replication study of GWAS-derived lipid genes in Asian Indians: The chromosomal region 11q23.3 harbors loci contributing to triglycerides, PLOS ONE, Vol: 7, Pages: 1-12, ISSN: 1932-6203
Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD.
Tan ST, Sehmi J, Al-Hussaini A, et al., 2012, NUCLEAR MAGNETIC RESONANCE PROFILING OF SERUM IDENTIFIES NOVEL BIOMARKER ASSOCIATED WITH CORONARY ATHEROSCLEROSIS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: B M J PUBLISHING GROUP, Pages: A83-A83, ISSN: 1355-6037
Chambers JC, Tan ST, Zhang WH, et al., 2012, WHOLE GENOME SEQUENCING TO IDENTIFY GENETIC VARIANTS UNDERLYING CARDIOVASCULAR DISEASE AMONG INDIAN ASIANS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: B M J PUBLISHING GROUP, Pages: A64-A64, ISSN: 1355-6037
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- Citations: 2
Li H, Kilpelaeinen TO, Liu C, et al., 2012, Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians, Diabetologia, Vol: 55, Pages: 981-995, ISSN: 0012-186X
Aims/hypothesisFTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r 2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.ResultsThe FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.Conclusions/interpretationFTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and simila
Sarwar N, Butterworth AS, Freitag DF, et al., 2012, Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies, LANCET, Vol: 379, Pages: 1205-1213, ISSN: 0140-6736
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- Citations: 580
Al-Hussaini A, Sehmi J, Tan T, et al., 2012, IDENTIFICATION OF NOVEL METABOLIC BIOMARKERS FOR CARDIOVASCULAR MORTALITY, 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: E1649-E1649, ISSN: 0735-1097
Dastani Z, Hivert M-F, Timpson N, et al., 2012, Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals, PLOS Genetics, Vol: 8, ISSN: 1553-7390
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inverselyassociated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wideassociation studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. Weidentified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.561028–1.2610243). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, andN = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samplesrevealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations afteraccounting for multiple testing (p,361024). We next developed a multi-SNP genotypic risk score to test the associationof adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This riskscore was associated with increased risk of T2D (p = 4.361023, n = 22,044), increased triglycerides (p = 2.6610214,n = 93,440), increased waist-to-hip ratio (p = 1.861025, n = 77,167), increased glucose two hours post oral glucosetolerance testing (p = 4.461023, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDLcholesterolconcentrations (p = 4.5610213, n = 96,748) and decreased BMI (p = 1.461024, n = 121,335). These findingsidentify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers ofinsulin resistance.
Clarke R, Bennett DA, Parish S, et al., 2012, Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias, PLoS Medicine, Vol: 9, Pages: 1-12, ISSN: 1549-1277
BackgroundModerately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality.Methods and FindingsNineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases).ConclusionsThe CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems.
Hoggart CJ, O'Reilly PF, Kaakinen M, et al., 2012, Fine-Scale Estimation of Location of Birth from Genome-Wide Single-Nucleotide Polymorphism Data, GENETICS, Vol: 190, Pages: 669-U583, ISSN: 0016-6731
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- Citations: 7
Gieger C, Radhakrishnan A, Cvejic A, et al., 2011, New gene functions in megakaryopoiesis and platelet formation, NATURE, Vol: 480, Pages: 201-208, ISSN: 0028-0836
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- Citations: 310
Bathula R, Hughes AD, Panerai RB, et al., 2011, South Asians have adverse cerebrovascular haemodynamics, despite equivalent blood pressure, compared with Europeans. This is due to their greater hyperglycaemia, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 40, Pages: 1490-1498, ISSN: 0300-5771
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- Citations: 15
Chambers JC, Zhang W, Sehmi J, et al., 2011, Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma, NATURE GENETICS, Vol: 43, Pages: 1131-1138, ISSN: 1061-4036
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- Citations: 409
Ehret GB, Munroe PB, Rice KM, et al., 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk, NATURE, Vol: 478, Pages: 103-109, ISSN: 0028-0836
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- Citations: 1509
Kooner JS, Saleheen D, Sim X, et al., 2011, Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci, NATURE GENETICS, Vol: 43, Pages: 984-U94, ISSN: 1061-4036
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- Citations: 398
Wain LV, Verwoert GC, O'Reilly PF, et al., 2011, Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure, NATURE GENETICS, Vol: 43, Pages: 1005-U122, ISSN: 1061-4036
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans1,2,3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10−8 to P = 2.3 × 10−13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Butterworth AS, Braund PS, Farrall M, et al., 2011, Large-scale gene-centric analysis identifies novel variants for coronary Artery disease, PLoS Genetics, Vol: 7, ISSN: 1553-7390
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse bioc
Fraser SDS, Parkes J, Roderick PJ, et al., 2011, SOCIO-DEMOGRAPHIC AND BEHAVIOURAL DETERMINANTS OF ABNORMAL LIVER FUNCTION IN A MULTI ETHNIC POPULATION IN THE UK: THE LOLIPOP STUDY, GUT, Vol: 60, Pages: A4-A4, ISSN: 0017-5749
Chahal NS, Lim TK, Jain P, et al., 2011, Does subclinical atherosclerosis burden identify the increased risk of cardiovascular disease mortality among United Kingdom Indian Asians? A population study, AMERICAN HEART JOURNAL, Vol: 162, Pages: 460-466, ISSN: 0002-8703
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- Citations: 9
Sehmi J, Das D, Ahmed N, et al., 2011, Unrecognized myocardial infarction in the London Life Sciences Population (LOLIPOP) study, Publisher: OXFORD UNIV PRESS, Pages: 751-751, ISSN: 0195-668X
Kilpelainen TO, Zillikens MC, Stancakova A, et al., 2011, Genetic variation near <i>IRS1</i> associates with reduced adiposity and an impaired metabolic profile, NATURE GENETICS, Vol: 43, Pages: 753-U58, ISSN: 1061-4036
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- Citations: 229
Schumann G, Coin LJ, Lourdusamy A, et al., 2011, Genome-wide association and genetic functional studies identify <i>autism susceptibility candidate 2</i> gene (AUTS2) in the regulation of alcohol consumption (vol 108, pg 7119, 2011), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 9316-9316, ISSN: 0027-8424
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