ProfessorPaulElliott

Garcia-Perez I, Villaseñor A, Wijeyesekera A, Posma JM, Stamler J, Aronson PS, Elliott P, Unwin R, Barbas C, Nicholson JK, Holmes Eet al., 2012, Urinary metabolic phenotyping the slc26a6 (chloride-oxalate exchanger) null mouse model, Journal of Proteome Research, Vol: 11, Pages: 4425-4435, ISSN: 1535-3893

The prevalence of renal stone disease is increasing, although it remains higher in men than in women when matched for age. While still somewhat controversial, several studies have reported an association between renal stone disease and hypertension, but this may be confounded by a shared link with obesity. However, independent of obesity, hyperoxaluria has been shown to be associated with hypertension in stone-formers and the most common type of renal stone is composed of calcium oxalate. The chloride-oxalate exchanger slc26a6 (also known as CFEX or PAT-1), located in the renal proximal tubule, was originally thought to have an important role in sodium homeostasis and thereby blood pressure control, but it has recently been shown to have a key function in oxalate balance by mediating oxalate secretion in the gut. We have applied two orthogonal analytical platforms (NMR spectroscopy and capillary-electrophoresis with UV detection) in parallel to characterize the urinary metabolic signatures related to the loss of the renal chloride-oxalate exchanger in slc26a6 null mice. Clear metabolic differentiation between the urinary profiles of the slc26a6 null and the wild type mice were observed using both methods, with the combination of NMR and CE-UV providing extensive coverage of the urinary metabolome. Key discriminating metabolites included oxalate, m-hydroxyphenylpropionylsulfate (m-HPPS), trimethylamine-N-oxide, glycolate and scyllo-inositol (higher in CFEX null mice) and hippurate, taurine, trimethylamine, and citrate (lower in slc26a6 null mice). In addition to the reduced efficiency of anion transport, several of these metabolites (hippurate, m-HPPS, methylamines) reflect alteration in gut microbial co-metabolic activities. Gender-related metabotypes were also observed in both wild type and slc26a6 null groups. Other urinary chemicals that showed a gender-specific pattern included trimethylamine, trimethylamine-N-oxide, citrate, spermidine, guanidinoacetate, and 2-

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Fox CS, Liu Y, White CC, Feitosa M, Smith AV, Heard-Costa N, Lohman K, GIANT Consortium, MAGIC Consortium, GLGC Consortium, Johnson AD, Foster MC, Greenawalt DM, Griffin P, Ding J, Newman AB, Tylavsky F, Miljkovic I, Kritchevsky SB, Launer L, Garcia M, Eiriksdottir G, Carr JJ, Gudnason V, Harris TB, Cupples LA, Borecki IBet al., 2012, Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women., PLOS Genetics, Vol: 8, ISSN: 1553-7390

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat reveale

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O'Reilly PF, Hoggart CJ, Pomyen Y, Calboli FCF, Elliott P, Jarvelin M-R, Coin LJMet al., 2012, MultiPhen: Joint Model of Multiple Phenotypes Can Increase Discovery in GWAS, PLOS One, Vol: 7, ISSN: 1932-6203

The genome-wide association study (GWAS) approach has discovered hundreds of genetic variants associated with diseasesand quantitative traits. However, despite clinical overlap and statistical correlation between many phenotypes, GWAS aregenerally performed one-phenotype-at-a-time. Here we compare the performance of modelling multiple phenotypes jointlywith that of the standard univariate approach. We introduce a new method and software, MultiPhen, that models multiplephenotypes simultaneously in a fast and interpretable way. By performing ordinal regression, MultiPhen tests the linearcombination of phenotypes most associated with the genotypes at each SNP, and thus potentially captures effects hiddento single phenotype GWAS. We demonstrate via simulation that this approach provides a dramatic increase in power inmany scenarios. There is a boost in power for variants that affect multiple phenotypes and for those that affect only onephenotype. While other multivariate methods have similar power gains, we describe several benefits of MultiPhen overthese. In particular, we demonstrate that other multivariate methods that assume the genotypes are normally distributed,such as canonical correlation analysis (CCA) and MANOVA, can have highly inflated type-1 error rates when testing casecontrolor non-normal continuous phenotypes, while MultiPhen produces no such inflation. To test the performance ofMultiPhen on real data we applied it to lipid traits in the Northern Finland Birth Cohort 1966 (NFBC1966). In these dataMultiPhen discovers 21% more independent SNPs with known associations than the standard univariate GWAS approach,while applying MultiPhen in addition to the standard approach provides 37% increased discovery. The most associatedlinear combinations of the lipids estimated by MultiPhen at the leading SNPs accurately reflect the Friedewald Formula,suggesting that MultiPhen could be used to refine the definition of existing phenotypes or uncover novel heritablepheno

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Ikram MA, Fornage M, Smith AV, Seshadri S, Schmidt R, Debette S, Vrooman HA, Sigurdsson S, Ropele S, Taal HR, Mook-Kanamori DO, Coker LH, Longstreth WT, Niessen WJ, DeStefano AL, Beiser A, Zijdenbos AP, Struchalin M, Jack CR, Rivadeneira F, Uitterlinden AG, Knopman DS, Hartikainen A-L, Pennell CE, Thiering E, Steegers EAP, Hakonarson H, Heinrich J, Palmer LJ, Jarvelin M-R, McCarthy MI, Grant SFA, St Pourcain B, Timpson NJ, Smith GD, Sovio U, Nalls MA, Au R, Hofman A, Gudnason H, van der Lugt A, Harris TB, Meeks WM, Vernooij MW, van Buchem MA, Catellier D, Jaddoe VWV, Gudnason V, Windham BG, Wolf PA, van Duijn CM, Mosley TH, Schmidt H, Launer LJ, Breteler MMB, DeCarli C, Adair LS, Ang W, Atalay M, vanBeijsterveldt T, Bergen N, Benke K, Berry D, Coin L, Davis OSP, Elliott P, Flexeder C, Frayling T, Gaillard R, Groen-Blokhuis M, Goh L-K, Haworth CMA, Hadley D, Hedebrand J, Hinney A, Hirschhorn JN, Holloway JW, Holst C, Hottenga JJ, Horikoshi M, Huikari V, Hypponen E, Kilpelainen TO, Kirin M, Kowgier M, Lakka H-M, Lange LA, Lawlor DA, Lehtimaki T, Lewin A, Lindgren C, Lindi V, Maggi R, Marsh J, Middeldorp C, Millwood I, Murray JC, Nivard M, Nohr EA, Ntalla I, Oken E, Panoutsopoulou K, Pararajasingham J, Rodriguez A, Salem RM, Sebert S, Siitonen N, Strachan DP, Teo Y-Y, Valcarcel B, Willemsen G, Zeggini E, Boomsma DI, Cooper C, Gillman M, Hocher B, Lakka TA, Mohlke KL, Dedoussis GV, Ong KK, Pearson ER, Price TS, Power C, Raitakari OT, Saw S-M, Scherag A, Simell O, Sorensen TIA, Wilson JFet al., 2012, Common variants at 6q22 and 17q21 are associated with intracranial volume, NATURE GENETICS, Vol: 44, Pages: 539-+, ISSN: 1061-4036

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• Citations: 105

, 2012, A genome-wide association meta-analysis identifies new childhood obesity loci, Nat Genet, Vol: 44, Pages: 526-531, ISSN: 1061-4036

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Chambers JC, Tan ST, Zhang WH, Sehmi J, Al-Hussaini A, Ramasamy M, Scott J, Elliott P, Kooner JSet 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

Tan ST, Sehmi J, Al-Hussaini A, Ala-Korpela M, Elliott P, Chambers JC, Kooner JSet 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

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Taal HR, St Pourcain B, Thiering E, Das S, Mook-Kanamori DO, Warrington NM, Kaakinen M, Kreiner-Moller E, Bradfield JP, Freathy RM, Geller F, Guxens M, Cousminer DL, Kerkhof M, Timpson NJ, Ikram MA, Beilin LJ, Bonnelykke K, Buxton JL, Charoen P, Chawes BLK, Eriksson J, Evans DM, Hofman A, Kemp JP, Kim CE, Klopp N, Lahti J, Lye SJ, McMahon G, Mentch FD, Muller-Nurasyid M, O'Reilly PF, Prokopenko I, Rivadeneira F, Steegers EAP, Sunyer J, Tiesler C, Yaghootkar H, Breteler MMB, Debette S, Fornage M, Gudnason V, Launer LJ, van der Lugt A, Mosley TH, Seshadri S, Smith AV, Vernooij MW, Blakemore AIF, Chiavacci RM, Feenstra B, Fernandez-Banet J, Grant SFA, Hartikainen A, van der Heijden AJ, Iniguez C, Lathrop M, McArdle WL, Molgaard A, Newnham JP, Palmer LJ, Palotie A, Pouta A, Ring SM, Sovio U, Standl M, Uitterlinden AG, Wichmann H, Vissing NH, DeCarli C, van Duijn CM, McCarthy MI, Koppelman GH, Estivill X, Hattersley AT, Melbye M, Bisgaard H, Pennell CE, Widen E, Hakonarson H, Smith GD, Heinrich J, Jarvelin M, Jaddoe VWVet al., 2012, Common variants at 12q15 and 12q24 are associated with infant head circumference, Nat Genet, Vol: 44, Pages: 532-538, ISSN: 1061-4036

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Repacholi MH, Lerchl A, Roosli M, Sienkiewicz Z, Auvinen A, Breckenkamp J, d'Inzeo G, Elliott P, Frei P, Heinrich S, Lagroye I, Lahkola A, McCormick DL, Thomas S, Vecchia Pet al., 2012, Systematic review of wireless phone use and brain cancer and other head tumors, BIOELECTROMAGNETICS, Vol: 33, Pages: 187-206, ISSN: 0197-8462

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• Citations: 61

Khan SA, Emadossadaty S, Ladep NG, Thomas HC, Elliott P, Taylor-Robinson SD, Toledano MBet al., 2012, Rising trends in cholangiocarcinoma: Is the ICD classification system misleading us?, JOURNAL OF HEPATOLOGY, Vol: 56, Pages: 848-854, ISSN: 0168-8278

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• Citations: 213

Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T, Yengo L, Kimura I, Leloire A, Liu N, Iida K, Choquet H, Besnard P, Lecoeur C, Vivequin S, Ayukawa K, Takeuchi M, Ozawa K, Tauber M, Maffeis C, Morandi A, Buzzetti R, Elliott P, Pouta A, Jarvelin M-R, Koerner A, Kiess W, Pigeyre M, Caiazzo R, Van Hul W, Van Gaal L, Horber F, Balkau B, Levy-Marchal C, Rouskas K, Kouvatsi A, Hebebrand J, Hinney A, Scherag A, Pattou F, Meyre D, Koshimizu T-A, Wolowczuk I, Tsujimoto G, Froguel Pet al., 2012, Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human, NATURE, Vol: 483, Pages: 350-U149, ISSN: 0028-0836

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• Citations: 498

Froguel P, Ndiaye NC, Bonnefond A, Bouatia-Naji N, Dechaume A, Siest G, Herbeth B, Falchi M, Bottolo L, Gueant-Rodriguez R-M, Lecoeur C, Langlois MR, Labrune Y, Ruokonen A, El Shamieh S, Stathopoulou MG, Morandi A, Maffeis C, Meyre D, Delanghe JR, Jacobson P, Sjostrom L, Carlsson LMS, Walley A, Elliott P, Jarvelin M-R, Dedoussis GV, Visvikis-Siest Set al., 2012, A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels, PLOS One, Vol: 7, ISSN: 1932-6203

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes toaid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobinlevels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases,including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acutemyocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulatinghaptoglobin levels has not been conducted so far. We used a genome-wide association study initially conducted in 631French children followed by a replication in three additional European sample sets and we identified a common singlenucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulatingHaptoglobin levels (Poverall = 8.1610259), explaining 45.4% of its genetic variability (11.8% of Hp global variance). Thefunctional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (b = 0.2360.08,P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789European children (Ptotal cholesterol = 0.002 and PLDL = 0.0008). Given the central position of haptoglobin in manyinflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobinconcentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact.

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Dastani Z, Hivert M-F, Timpson N, Perry JRB, Yuan X, Scott RA, Henneman P, Heid IM, Kizer JR, Lyytikainen L-P, Fuchsberger C, Tanaka T, Morris AP, Small K, Isaacs A, Beekman M, Coassin S, Lohman K, Qi L, Kanoni S, Pankow JS, Uh H-W, Wu Y, Bidulescu A, Rasmussen-Torvik LJ, Greenwood CMT, Ladouceur M, Grimsby J, Manning AK, Liu C-T, Kooner J, Mooser VE, Vollenweider P, Kapur KA, Chambers J, Wareham NJ, Langenberg C, Frants R, Willems-vanDijk K, Oostra BA, Willems SM, Lamina C, Winkler TW, Psaty BM, Tracy RP, Brody J, Chen I, Viikari J, Kahonen M, Pramstaller PP, Evans DM, St Pourcain B, Sattar N, Wood AR, Bandinelli S, Carlson OD, Egan JM, Bohringer S, van Heemst D, Kedenko L, Kristiansson K, Nuotio M-L, Loo B-M, Harris T, Garcia M, Kanaya A, Haun M, Klopp N, Wichmann H-E, Deloukas P, Katsareli E, Couper DJ, Duncan BB, Kloppenburg M, Adair LS, Borja JB, Wilson JG, Musani S, Guo X, Johnson T, Semple R, Teslovich TM, Allison MA, Redline S, Buxbaum SG, Mohlke KL, Meulenbelt I, Ballantyne CM, Dedoussis GV, Hu FB, Liu Y, Paulweber B, Spector TD, Slagboom PE, Ferrucci L, Jula A, Perola M, Raitakari O, Florez JC, Salomaa V, Eriksson JG, Frayling TM, Hicks AA, Lehtimaki T, Smith GD, Siscovick DS, Kronenberg F, van Duijn C, Loos RJF, Waterworth DM, Meigs JB, Dupuis J, Richards JBet 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.

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Loo RL, Chan Q, Brown IJ, Robertson CE, Stamler J, Nicholson JK, Holmes E, Elliott Pet al., 2012, A Comparison of Self-Reported Analgesic Use and Detection of Urinary Ibuprofen and Acetaminophen Metabolites by Means of Metabonomics The INTERMAP Study, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 175, Pages: 348-358, ISSN: 0002-9262

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• Citations: 27

Creemers JWM, Choquet H, Stijnen P, Vatin V, Pigeyre M, Beckers S, Meulemans S, Than ME, Yengo L, Tauber M, Balkan B, Elliott P, Jarvelin M-R, Van Hul W, Van Gaal L, Horber F, Pattou F, Froguel P, Meyre Det al., 2012, Heterozygous Mutations Causing Partial Prohormone Convertase 1 Deficiency Contribute to Human Obesity, Diabetes, Vol: 61, Pages: 383-390, ISSN: 0012-1797

Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.

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Mitchell GF, Verwoert GC, Tarasov KV, Isaacs A, Smith AV, Yasmin, Rietzschel ER, Tanaka T, Liu Y, Parsa A, Najjar SS, O'Shaughnessy KM, Sigurdsson S, De Buyzere ML, Larson MG, Sie MPS, Andrews JS, Post WS, Mattace-Raso FUS, McEniery CM, Eiriksdottir G, Segers P, Vasan RS, van Rijn MJE, Howard TD, McArdle PF, Dehghan A, Jewell ES, Newhouse SJ, Bekaert S, Hamburg NM, Newman AB, Hofman A, Scuteri A, De Bacquer D, Ikram MA, Psaty BM, Fuchsberger C, Olden M, Wain LV, Elliott P, Smith NL, Felix JF, Erdmann J, Vita JA, Sutton-Tyrrell K, Sijbrands EJG, Sanna S, Launer LJ, De Meyer T, Johnson AD, Schut AFC, Herrington DM, Rivadeneira F, Uda M, Wilkinson IB, Aspelund T, Gillebert TC, Van Bortel L, Benjamin EJ, Oostra BA, Ding J, Gibson Q, Uitterlinden AG, Abecasis GR, Cockcroft JR, Gudnason V, De Backer GG, Ferrucci L, Harris TB, Shuldiner AR, van Duijn CM, Levy D, Lakatta EG, Witteman JCMet al., 2012, Common Genetic Variation in the 3′-<i>BCL11B</i> Gene Desert Is Associated With Carotid-Femoral Pulse Wave Velocity and Excess Cardiovascular Disease Risk The AortaGen Consortium, CIRCULATION-CARDIOVASCULAR GENETICS, Vol: 5, Pages: 81-90, ISSN: 1942-325X

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• Citations: 71

Palmer ND, McDonough CW, Hicks PJ, Roh BH, Wing MR, An SS, Hester JM, Cooke JN, Bostrom MA, Rudock ME, Talbert ME, Lewis JP, DIAGRAM Consortium, MAGIC Investigators, Ferrara A, Lu L, Ziegler JT, Sale MM, Divers J, Shriner D, Adeyemo A, Rotimi CN, Ng MC, Langefeld CD, Freedman BI, Bowden DW, Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segrè AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladeket al., 2012, A genome-wide association search for type 2 diabetes genes in African Americans., PLOS One, Vol: 7, ISSN: 1932-6203

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

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Wijeyesekera A, Clarke PA, Bictash M, Brown IJ, Fidock M, Ryckmans T, Yap IKS, Chan Q, Stamler J, Elliott P, Holmes E, Nicholson JKet al., 2012, Quantitative UPLC-MS/MS analysis of the gut microbial co-metabolites phenylacetylglutamine, 4-cresyl sulphate and hippurate in human urine: INTERMAP Study, ANALYTICAL METHODS, Vol: 4, Pages: 65-72, ISSN: 1759-9660

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• Citations: 28

Ward H, Toledano MB, Shaddick G, Davies Bet al., 2012, Oxford Handbook of Epidemiology for Clinicians, Oxford Handbook of Epidemiology for Clinicians, Editors: Ward, Toledano, Shaddick, Davies, Elliott, Oxford UK, Publisher: Oxford University Press, Pages: 1-388, ISBN: 978-0-19-852988-0

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Ward H, Toledano MB, Shaddick G, Davies Bet al., 2012, Oxford Handbook of Epidemiology for Clinicians 978-0-19-852988-0, Oxford UK, Publisher: Oxford University Press, ISBN: 978-0-19-852988-0

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Johnson T, Gaunt TR, Newhouse SJ, Padmanabhan S, Tomaszewski M, Kumari M, Morris RW, Tzoulaki I, O'Brien ET, Poulter NR, Sever P, Shields DC, Thom S, Wannamethee SG, Whincup PH, Brown MJ, Connell JM, Dobson RJ, Howard PJ, Mein CA, Onipinla A, Shaw-Hawkins S, Zhang Y, Smith GD, Day INM, Lawlor DA, Goodall AH, Fowkes FG, Abecasis GR, Elliott P, Gateva V, Braund PS, Burton PR, Nelson CP, Tobin MD, van der Harst P, Glorioso N, Neuvrith H, Salvi E, Staessen JA, Stucchi A, Devos N, Jeunemaitre X, Plouin P-F, Tichet J, Juhanson P, Org E, Putku M, Sober S, Veldre G, Viigimaa M, Levinsson A, Rosengren A, Thelle DS, Hastie CE, Hedner T, Lee WK, Melander O, Wahlstrand B, Hardy R, Wong A, Cooper JA, Palmen J, Chen L, Stewart AFR, Wells GA, Westra H-J, Wolfs MGM, Clarke R, Franzosi MG, Goel A, Hamsten A, Lathrop M, Peden JF, Seedorf U, Watkins H, Ouwehand WH, Sambrook J, Stephens J, Casas J-P, Drenos F, Holmes MV, Kivimaki M, Shah S, Shah T, Talmud PJ, Whittaker J, Wallace C, Delles C, Laan M, Kuh D, Humphries SE, Nyberg F, Cusi D, Roberts R, Newton-Cheh C, Franke L, Stanton AV, Dominiczak AF, Farrall M, Hingorani AD, Samani NJ, Caulfield MJ, Munroe PBet al., 2011, Blood Pressure Loci Identified with a Gene-Centric Array, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 89, Pages: 688-700, ISSN: 0002-9297

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Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic-Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Maegi R, Meacham S, Okada Y, Pirastu N, Sorice R, Teumer A, Voss K, Zhang W, Ramirez-Solis R, Bis JC, Ellinghaus D, Goegele M, Hottenga J-J, Langenberg C, Kovacs P, O'Reilly PF, Shin S-Y, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot CE, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, D'Adamo P, Davies G, de Boer RA, de Geus EJC, Doering A, Elliott P, Erdmann J, Evans DM, Falchi M, Feng W, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen A-L, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJF, Jolley J, Khaw KT, Kuehnel B, Kyrtsonis M-C, Lagou V, Lloyd-Jones H, Lumley T, Mangino M, Maschio A, Leach IM, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nakamura Y, Nauck M, Navis G, Noethlings U, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Tang WHW, Taylor K, Tenesa A, Thein SL, Toenjes A, Uda M, Ulivi S, van Veldhuisen DJ, Visscher PM, Voelker U, Wichmann H-E, Wiggins KL, Willemsen G, Yang T-P, Zhao JH, Zitting P, Bradley JR, Dedoussis GV, Gasparini P, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, van Pelt LJ, Zwaginga J-J, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin M-R, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman J-WN, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Rendon A, Ferreira MA, Ouwehand WH, Soranzo Net al., 2011, New gene functions in megakaryopoiesis and platelet formation, NATURE, Vol: 480, Pages: 201-208, ISSN: 0028-0836

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Pitcher A, Ashby D, Elliott P, Petersen SEet al., 2011, Cardiac MRI as end point in clinical trials reply, HEART, Vol: 97, Pages: 1991-1991, ISSN: 1355-6037

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Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga J-J, Kuehnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Leach IM, O'Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJC, Dixon AL, Doering A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen A-L, Heath S, Hirschfield GM, Hofman A, Homuth G, Hyppoenen E, Janssen HLA, Johnson T, Kangas AJ, Kema IP, Kuehn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin J-P, Loos RJF, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O'Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JNL, Seedorf U, Sen-Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, Van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann H-E, Willemsen G, Wuertz P, Xu C, Yerges-Armstrong LM, Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietilainen KH, Schumann G, Snieder H, Sternberg MJE, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JCM, Wolffenbuttel BHR, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Voelzke H, Schadt EE, Scott J, Jarvelin M-R, Elliott P, Kooner JSet 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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Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Maegi R, Workalemahu T, White CC, Bouatia-Naji N, Harris TB, Berndt SI, Ingelsson E, Willer CJ, Weedon MN, Luan J, Vedantam S, Esko T, Kilpelaeinen TO, Kutalik Z, Li S, Monda KL, Dixon AL, Holmes CC, Kaplan LM, Liang L, Min JL, Moffatt MF, Molony C, Nicholson G, Schadt EE, Zondervan KT, Feitosa MF, Ferreira T, Allen HL, Weyant RJ, Wheeler E, Wood AR, Estrada K, Goddard ME, Lettre G, Mangino M, Nyholt DR, Purcell S, Smith AV, Visscher PM, Yang J, McCarroll SA, Nemesh J, Voight BF, Absher D, Amin N, Aspelund T, Coin L, Glazer NL, Hayward C, Heard-Costa NL, Hottenga J-J, Johansson A, Johnson T, Kaakinen M, Kapur K, Ketkar S, Knowles JW, Kraft P, Kraja AT, Lamina C, Leitzmann MF, McKnight B, Morris AP, Ong KK, Perry JRB, Peters MJ, Polasek O, Prokopenko I, Rayner NW, Ripatti S, Rivadeneira F, Robertson NR, Sanna S, Sovio U, Surakka I, Teumer A, van Wingerden S, Vitart V, Zhao JH, Cavalcanti-Proenca C, Chines PS, Fisher E, Kulzer JR, Lecoeur C, Narisu N, Sandholt C, Scott LJ, Silander K, Stark K, Tammesoo M-L, Teslovich TM, Timpson NJ, Watanabe RM, Welch R, Chasman DI, Cooper MN, Jansson J-O, Kettunen J, Lawrence RW, Pellikka N, Perola M, Vandenput L, Alavere H, Almgren P, Atwood LD, Bennett AJ, Biffar R, Bonnycastle LL, Bornstein SR, Buchanan TA, Campbell H, Day INM, Dei M, Doerr M, Elliott P, Erdos MR, Eriksson JG, Freimer NB, Fu M, Gaget S, Geus EJC, Gjesing AP, Grallert H, Graessler J, Groves CJ, Guiducci C, Hartikainen A-L, Hassanali N, Havulinna AS, Herzig K-H, Hicks AA, Hui J, Igl W, Jousilahti P, Jula A, Kajantie E, Kinnunen L, Kolcic I, Koskinen S, Kovacs P, Kroemer HK, Krzelj V, Kuusisto J, Kvaloy K, Laitinen J, Lantieri O, Lathrop GM, Lokki M-L, Luben RN, Ludwig B, McArdle WL, McCarthy A, Morken MA, Nelis M, Neville MJ, Pare G, Parker AN, Peden JF, Pichler I, Pietilaeinen KH, Platou CGP, Pouta A, Ridderstrale M, Samani NJ, Saramies J, Sinisalo Jet al., 2011, Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution, NATURE GENETICS, Vol: 43, Pages: 1164-1164, ISSN: 1061-4036

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Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang S-J, Pihur V, Vollenweider P, O'Reilly PF, Amin N, Bragg-Gresham JL, Teumer A, Glazer NL, Launer L, Zhao JH, Aulchenko Y, Heath S, Sober S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Go MJ, van der Harst P, Kao WHL, Sjogren M, Vinay DG, Alexander M, Tabara Y, Shaw-Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Khanh-Dung HN, Lehtimaki T, Matullo G, Wu Y, Gaunt TR, Onland-Moret NC, Cooper MN, Platou CGP, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CSPM, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang Y-PC, O'Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day INM, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Hopewell JC, Ongen H, Dreisbach AW, Li Y, Young JH, Bis JC, Kahonen M, Viikari J, Adair LS, Lee NR, Chen M-H, Olden M, Pattaro C, Bolton JAH, Koettgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Graessler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso IS, Khaw K-T, Weder AB, Hunt SC, Sun YV, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand S-M, Staessen JA, Wang TJ, Burton PR, Artigas MS, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Doumatey A, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Corsi AM, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshimet 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

Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist E, Rybin D, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, Nica A, Wheeler E, Chen H, Voight BF, Taneera J, Kanoni S, Peden JF, Turrini F, Gustafsson S, Zabena C, Almgren P, Barker DJP, Barnes D, Dennison EM, Eriksson JG, Eriksson P, Eury E, Folkersen L, Fox CS, Frayling TM, Goel A, Gu HF, Horikoshi M, Isomaa B, Jackson AU, Jameson KA, Kajantie E, Kerr-Conte J, Kuulasmaa T, Kuusisto J, Loos RJF, Luan J, Makrilakis K, Manning AK, Teresa Martinez-Larrad M, Narisu N, Mannila MN, Ohrvik J, Osmond C, Pascoe L, Payne F, Sayer AA, Sennblad B, Silveira A, Stancakova A, Stirrups K, Swift AJ, Syvanen A-C, Tuomi T, van 't Hooft FM, Walker M, Weedon MN, Xie W, Zethelius B, Ongen H, Malarstig A, Hopewell JC, Saleheen D, Chambers J, Parish S, Danesh J, Kooner J, Ostenson C-G, Lind L, Cooper CC, Serrano-Rios M, Ferrannini E, Forsen TJ, Clarke R, Franzosi MG, Seedorf U, Watkins H, Froguel P, Johnson P, Deloukas P, Collins FS, Laakso M, Dermitzakis ET, Boehnke M, McCarthy MI, Wareham NJ, Groop L, Pattou F, Gloyn AL, Dedoussis GV, Lyssenko V, Meigs JB, Barroso I, Watanabe RM, Ingelsson E, Langenberg C, Hamsten A, Florez JCet al., 2011, Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes, Diabetes, Vol: 60, Pages: 2624-2634, ISSN: 0012-1797

OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates.RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets.CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.

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Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia K-S, Dimas AS, Hassanali N, Jafar T, Jowett JBM, Li X, Radha V, Rees SD, Takeuchi F, Young R, Aung T, Basit A, Chidambaram M, Das D, Grundberg E, Hedman AK, Hydrie ZI, Islam M, Khor C-C, Kowlessur S, Kristensen MM, Liju S, Lim W-Y, Matthews DR, Liu J, Morris AP, Nica AC, Pinidiyapathirage JM, Prokopenko I, Rasheed A, Samuel M, Shah N, Shera AS, Small KS, Suo C, Wickremasinghe AR, Wong TY, Yang M, Zhang F, Abecasis GR, Barnett AH, Caulfield M, Deloukas P, Frayling TM, Froguel P, Kato N, Katulanda P, Kelly MA, Liang J, Mohan V, Sanghera DK, Scott J, Seielstad M, Zimmet PZ, Elliott P, Teo YY, McCarthy MI, Danesh J, Tai ES, Chambers JCet 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

Soler Artigas M, Loth DW, Wain LV, Gharib SA, Obeidat M, Tang W, Zhai G, Zhao JH, Smith AV, Huffman JE, Albrecht E, Jackson CM, Evans DM, Cadby G, Fornage M, Manichaikul A, Lopez LM, Johnson T, Aldrich MC, Aspelund T, Barroso I, Campbell H, Cassano PA, Couper DJ, Eiriksdottir G, Franceschini N, Garcia M, Gieger C, Gislason GK, Grkovic I, Hammond CJ, Hancock DB, Harris TB, Ramasamy A, Heckbert SR, Heliovaara M, Homuth G, Hysi PG, James AL, Jankovic S, Joubert BR, Karrasch S, Klopp N, Koch B, Kritchevsky SB, Launer LJ, Liu Y, Loehr LR, Lohman K, Loos RJF, Lumley T, Al Balushi KA, Ang WQ, Barr RG, Beilby J, Blakey JD, Boban M, Boraska V, Brisman J, Britton JR, Brusselle GG, Cooper C, Curjuric I, Dahgam S, Deary IJ, Ebrahim S, Eijgelsheim M, Francks C, Gaysina D, Granell R, Gu X, Hankinson JL, Hardy R, Harris SE, Henderson J, Henry A, Hingorani AD, Hofman A, Holt PG, Hui J, Hunter ML, Imboden M, Jameson KA, Kerr SM, Kolcic I, Kronenberg F, Liu JZ, Marchini J, McKeever T, Morris AD, Olin A-C, Porteous DJ, Postma DS, Rich SS, Ring SM, Rivadeneira F, Rochat T, Sayer AA, Sayers I, Sly PD, Smith GD, Sood A, Starr JM, Uitterlinden AG, Vonk JM, Wannamethee SG, Whincup PH, Wijmenga C, Williams OD, Wong A, Mangino M, Marciante KD, McArdle WL, Meibohm B, Morrison AC, North KE, Omenaas E, Palmer LJ, Pietilainen KH, Pin I, Polasek O, Pouta A, Psaty BM, Hartikainen A-L, Rantanen T, Ripatti S, Rotter JI, Rudan I, Rudnicka AR, Schulz H, Shin S-Y, Spector TD, Surakka I, Vitart V, Voelzke H, Wareham NJ, Warrington NM, Wichmann H-E, Wild SH, Wilk JB, Wjst M, Wright AF, Zgaga L, Zemunik T, Pennell CE, Nyberg F, Kuh D, Holloway JW, Boezen HM, Lawlor DA, Morris RW, Probst-Hensch N, Kaprio J, Wilson JF, Hayward C, Kahonen M, Heinrich J, Musk AW, Jarvis DL, Glaeser S, Jarvelin M-R, Stricker BHC, Elliott P, O'Connor GT, Strachan DP, London SJ, Hall IP, Gudnason V, Tobin MDet al., 2011, Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function, NATURE GENETICS, Vol: 43, Pages: 1082-1090, ISSN: 1061-4036

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Wain LV, Verwoert GC, O'Reilly PF, Shi G, Johnson T, Johnson AD, Bochud M, Rice KM, Henneman P, Smith AV, Ehret GB, Amin N, Larson MG, Mooser V, Hadley D, Doerr M, Bis JC, Aspelund T, Esko T, Janssens ACJW, Zhao JH, Heath S, Laan M, Fu J, Pistis G, Luan J, Arora P, Lucas G, Pirastu N, Pichler I, Jackson AU, Webster RJ, Zhang F, Peden JF, Schmidt H, Tanaka T, Campbell H, Igl W, Milaneschi Y, Hottenga J-J, Vitart V, Chasman DI, Trompet S, Bragg-Gresham JL, Alizadeh BZ, Chambers JC, Guo X, Lehtimaki T, Kuehnel B, Lopez LM, Polasek O, Boban M, Nelson CP, Morrison AC, Pihur V, Ganesh SK, Hofman A, Kundu S, Mattace-Raso FUS, Rivadeneira F, Sijbrands EJG, Uitterlinden AG, Hwang S-J, Vasan RS, Wang TJ, Bergmann S, Vollenweider P, Waeber G, Laitinen J, Pouta A, Zitting P, McArdle WL, Kroemer HK, Voelker U, Voelzke H, Glazer NL, Taylor KD, Harris TB, Alavere H, Haller T, Keis A, Tammesoo M-L, Aulchenko Y, Barroso I, Khaw K-T, Galan P, Hercberg S, Lathrop M, Eyheramendy S, Org E, Sober S, Lu X, Nolte IM, Penninx BW, Corre T, Masciullo C, Sala C, Groop L, Voight BF, Melander O, O'Donnell CJ, Salomaa V, d'Adamo AP, Fabretto A, Faletra F, Ulivi S, Del Greco FM, Facheris M, Collins FS, Bergman RN, Beilby JP, Hung J, Musk AW, Mangino M, Shin S-Y, Soranzo N, Watkins H, Goel A, Hamsten A, Gider P, Loitfelder M, Zeginigg M, Hernandez D, Najjar SS, Navarro P, Wild SH, Corsi AM, Singleton A, de Geus EJC, Willemsen G, Parker AN, Rose LM, Buckley B, Stott D, Orru M, Uda M, van der Klauw MM, Zhang W, Li X, Scott J, Chen Y-DI, Burke GL, Kahonen M, Viikari J, Doering A, Meitinger T, Davies G, Starr JM, Emilsson V, Plump A, Lindeman JH, 't Hoen PAC, Koenig IR, Felix JF, Clarke R, Hopewell JC, Ongen H, Breteler M, Debette S, DeStefano AL, Fornage M, Mitchell GF, Smith NL, Holm H, Stefansson K, Thorleifsson G, Thorsteinsdottir U, Samani NJ, Preuss M, Rudan I, Hayward C, Deary IJ, Wichmann H-E, Raitakari OT, Palmas W, Kooner JS, Stolk RP, Jukema JW, Wright AF, Boomsma DI, Bandinelli S, Gyllensteet 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.

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