ProfessorJohnChambers

Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka DC, Esko T, Fall T, Ferreira T, Gustafsson S, Kutalik Z, Luan J, Maegi R, Randall JC, Winkler TW, Wood AR, Workalemahu T, Faul JD, Smith JA, Zhao JH, Zhao W, Chen J, Fehrmann R, Hedman AK, Karjalainen J, Schmidt EM, Absher D, Amin N, Anderson D, Beekman M, Bolton JL, Bragg-Gresham L, Buyske S, Demirkan A, Deng G, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Goel A, Gong J, Jackson AU, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Leach IM, Medina-Gomez C, Medland SE, Nalls MA, Palmer CD, Pasko D, Pechlivanis S, Peters MJ, Prokopenko I, Shungin D, Stancakova A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Settee J, Van Vliet-Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Isaacs A, Albrecht E, Arnlov J, Arscott GM, Attwood AP, Bandinelli S, Barrett A, Bas IN, Bellis C, Bennett AJ, Berne C, Blagieva R, Blueher M, Bohringer S, Bonnycastle LL, Boettcher Y, Boyd HA, Bruinenberg M, Caspersen IH, Chen Y-DI, Clarke R, Daw EW, de Craen AJM, Delgado G, Dimitriou M, Doney ASF, Eklund N, Estrada K, Eury E, Folkersen L, Fraser RM, Garcia ME, Geller F, Giedraitis V, Gigante B, Go AS, Golay A, Goodall AH, Gordon SD, Gorski M, Grabe H-J, Grallert H, Grammer TB, Graessler J, Gronberg H, Groves CJ, Gusto G, Haessler J, Hall P, Haller T, Hallmans G, Hartman CA, Hassinen M, Hayward C, Heard-Costa NL, Helmer Q, Hengstenberg C, Holmen O, Hottenga J-J, James AL, Jeff JM, Johansson A, Jolley J, Juliusdottir T, Kinnunen L, Koenig W, Koskenvuo M, Kratzer W, Laitinen J, Lamina C, Leander K, Lee NR, Lichtner P, Lind L, Lindstrom J, Lo KS, Lobbens S, Lorbeer R, Lu Y, Mach F, Magnusson PKE, Mahajan A, McArdle WL, McLachlan S, Menni C, Merger S, Mihailov E, Milani L, Moayyeri A, Monda KL, Morken MA, Mulas A, Mueller G, Mueller-Nurasyid M, Musk AW, Nagaraja R, Noethen MM, Nolte IM, Pilz S, Rayner NW, Renstrom F, Rettig R, Ried JS, Ripkeet al., 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature, Vol: 518, Pages: 197-206, ISSN: 0028-0836

• Cite

Yaghootkar H, Scott RA, White CC, Zhang W, Speliotes E, Munroe PB, Ehret GB, Bis JC, Fox CS, Walker M, Borecki IB, Knowles JW, Yerges-Armstrong L, Ohlsson C, Perry JRB, Chambers JC, Kooner JS, Franceschini N, Langenberg C, Hivert M-F, Dastani Z, Richards JB, Semple RK, Frayling TMet al., 2014, Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes, Diabetes, Vol: 63, Pages: 4369-4377, ISSN: 0012-1797

The mechanisms that predispose to hypertension, coronary artery disease (CAD), and type 2 diabetes (T2D) in individuals of normal weight are poorly understood. In contrast, in monogenic primary lipodystrophy—a reduction in subcutaneous adipose tissue—it is clear that it is adipose dysfunction that causes severe insulin resistance (IR), hypertension, CAD, and T2D. We aimed to test the hypothesis that common alleles associated with IR also influence the wider clinical and biochemical profile of monogenic IR. We selected 19 common genetic variants associated with fasting insulin–based measures of IR. We used hierarchical clustering and results from genome-wide association studies of eight nondisease outcomes of monogenic IR to group these variants. We analyzed genetic risk scores against disease outcomes, including 12,171 T2D cases, 40,365 CAD cases, and 69,828 individuals with blood pressure measurements. Hierarchical clustering identified 11 variants associated with a metabolic profile consistent with a common, subtle form of lipodystrophy. A genetic risk score consisting of these 11 IR risk alleles was associated with higher triglycerides (β = 0.018; P = 4 × 10−29), lower HDL cholesterol (β = −0.020; P = 7 × 10−37), greater hepatic steatosis (β = 0.021; P = 3 × 10−4), higher alanine transaminase (β = 0.002; P = 3 × 10−5), lower sex-hormone-binding globulin (β = −0.010; P = 9 × 10−13), and lower adiponectin (β = −0.015; P = 2 × 10−26). The same risk alleles were associated with lower BMI (per-allele β = −0.008; P = 7 × 10−8) and increased visceral-to-subcutaneous adipose tissue ratio (β = −0.015; P = 6 × 10−7). Individuals carrying ≥17 fasting insulin–raising alleles (5.5% population) were slimmer (0.30 kg/m2) but at increased risk of T2D (odds ratio [OR] 1.46; per-allele P = 5

• Abstract
• Publisher Web Link
• Author Web Link
• Cite

Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chun AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau-Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Maegi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AAE, Westra H-J, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice AE, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Lui JC, Mangino M, Leach IM, Medina-Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancakova A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet-Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Arnloev J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blueher M, Bolton JL, Boettcher Y, Boyd HA, Bruinenberg M, Buckley BM, Buyske S, Caspersen IH, Chines PS, Clarke R, Claudi-Boehm S, Cooper M, Daw EW, De Jong PA, Deelen J, Delgado G, Denny JC, Dhonukshe-Rutten R, Dimitriou M, Doney ASF, Doerr M, Eklund N, Eury E, Folkersen L, Garcia ME, Geller F, Giedraitis V, Go AS, Grallert H, Grammer TB, Graessler J, Groenberg H, de Groot LCPGM, Groves CJ, Haessler J, Hall P, Haller T, Hallmans G, Hannemann A, Hartman CA, Hassinen M, Hayward C, Heard-Costa NL, Helmer Q, Hemani G, Henders AK, Hillege HL, Hlatky MA, Hoffmann W, Hoffmann P, Holmen O, Houwing-Duistermaat JJ, Illig T, Isaacs A, James AL, Jeff J, Johansen B, Johansson A, Jolley J, Juliusdottir T, Junttila J, Kho AN, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Lindstroem J, Lobbens S, Lorentzon M, Lu Y, Lyssenko V, Magnusson PKE, Mahajan A, Maillard M, McArdle WL, McKenzie CA, McLachlan S, McLaren PJ, Menni C, Merger S, Milani L, Moayyeri A, Monda KL, Morken MA, Mueller G, Mueller-Nurasyid M, Musk AW, Narisu N, Nauck M, Nolte IM, Noet al., 2014, Defining the role of common variation in the genomic and biological architecture of adult human height, Nature Genetics, Vol: 46, Pages: 1173-1186, ISSN: 1546-1718

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate–related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

• Abstract
• Author Web Link
• Open Access Link
• Cite

Xi B, Takeuchi F, Meirhaeghe A, Kato N, Chambers JC, Morris AP, Cho YS, Zhang W, Mohlke KL, Kooner JS, Shu XO, Pan H, Tai ES, Pan H, Wu J-Y, Zhou D, Chandak GRet al., 2014, Associations of genetic variants in/near body mass index-associated genes with type 2 diabetes: a systematic meta-analysis, CLINICAL ENDOCRINOLOGY, Vol: 81, Pages: 702-710, ISSN: 0300-0664

• Author Web Link
• Cite
• Citations: 29

Chen L, Kostadima M, Martens JHA, Canu G, Garcia SP, Turro E, Downes K, Macaulay IC, Bielczyk-Maczynska E, Coe S, Farrow S, Poudel P, Burden F, Jansen SBG, Astle WJ, Attwood A, Bariana T, de Bono B, Breschi A, Chambers JC, Choudry FA, Clarke L, Coupland P, van der Ent M, Erber WN, Jansen JH, Favier R, Fenech ME, Foad N, Freson K, van Geet C, Gomez K, Guigo R, Hampshire D, Kelly AM, Kerstens HHD, Kooner JS, Laffan M, Lentaigne C, Labalette C, Martin T, Meacham S, Mumford A, Nuernberg S, Palumbo E, van der Reijden BA, Richardson D, Sammut SJ, Slodkowicz G, Tamuri AU, Vasquez L, Voss K, Watt S, Westbury S, Flicek P, Loos R, Goldman N, Bertone P, Read RJ, Richardson S, Cvejic A, Soranzo N, Ouwehand WH, Stunnenberg HG, Frontini M, Rendon Aet al., 2014, Transcriptional diversity during lineage commitment of human blood progenitors, SCIENCE, Vol: 345, Pages: 1580-+, ISSN: 0036-8075

• Author Web Link
• Cite
• Citations: 185

Chambers JC, Abbott J, Zhang W, Turro E, Scott WR, Tan S-T, Afzal U, Afaq S, Loh M, Lehne B, O'Reilly P, Gaulton KJ, Pearson RD, Li X, Lavery A, Vandrovcova J, Wass MN, Miller K, Sehmi J, Oozageer L, Kooner IK, Al-Hussaini A, Mills R, Grewal J, Panoulas V, Lewin AM, Northwood K, Wander GS, Geoghegan F, Li Y, Wang J, Aitman TJ, McCarthy MI, Scott J, Butcher S, Elliott P, Kooner JSet al., 2014, The South Asian Genome, PLOS One, Vol: 9, ISSN: 1932-6203

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

• Abstract
• Open Access Link
• Cite

Hoggart CJ, Venturini G, Mangino M, Gomez F, Ascari G, Zhao JH, Teumer A, Winkler TW, Tsernikova N, Luan J, Mihailov E, Ehret GB, Zhang W, Lamparter D, Esko T, Mace A, Rueeger S, Bochud P-Y, Barcella M, Dauvilliers Y, Benyamin B, Evans DM, Hayward C, Lopez MF, Franke L, Russo A, Heid IM, Salvi E, Vendantam S, Arking DE, Boerwinkle E, Chambers JC, Fiorito G, Grallert H, Guarrera S, Homuth G, Huffman JE, Porteous D, Moradpour D, Iranzo A, Hebebrand J, Kemp JP, Lammers GJ, Aubert V, Heim MH, Martin NG, Montgomery GW, Peraita-Adrados R, Santamaria J, Negro F, Schmidt CO, Scott RA, Spector TD, Strauch K, Voelzke H, Wareham NJ, Yuan W, Bell JT, Chakravarti A, Kooner JS, Peters A, Matullo G, Wallaschofski H, Whitfield JB, Paccaud F, Vollenweider P, Bergmann S, Beckmann JS, Tafti M, Hastie ND, Cusi D, Bochud M, Frayling TM, Metspalu A, Jarvelin M-R, Scherag A, Smith GD, Borecki IB, Rousson V, Hirschhorn JN, Rivolta C, Loos RJF, Kutalik Zet al., 2014, Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index, PLOS Genetics, Vol: 10, ISSN: 1553-7390

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present anovel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. Themethod exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six leadSNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternalrs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCRexperiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent onparental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelatedindividuals to identify POEs and demonstrates that they play an important role in adult obesity.

• Abstract
• Open Access Link
• Cite

Ganesh SK, Chasman DI, Larson MG, Guo X, Verwoert G, Bis JC, Gu X, Smith AV, Yang M-L, Zhang Y, Ehret G, Rose LM, Hwang S-J, Papanicolau GJ, Sijbrands EJ, Rice K, Eiriksdottir G, Pihur V, Ridker PM, Vasan RS, Newton-Cheh C, Raffel LJ, Amin N, Rotter JI, Liu K, Launer LJ, Xu M, Caulfield M, Morrison AC, Johnson AD, Vaidya D, Dehghan A, Li G, Bouchard C, Harris TB, Zhang H, Boerwinkle E, Siscovick DS, Gao W, Uitterlinden AG, Rivadeneira F, Hofman A, Willer CJ, Franco OH, Huo Y, Witteman JCM, Munroe PB, Gudnason V, Palmas W, van Duijn C, Fornage M, Levy D, Psaty BM, Chakravarti Aet al., 2014, Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 95, Pages: 49-65, ISSN: 0002-9297

• Author Web Link
• Cite
• Citations: 55

Yaghootkar H, Scott R, White CC, Zhang W, Speliotes EK, Munroe PB, Ehret GB, Bis JC, Fox CS, Walker M, Borecki IB, Knowles JW, Yerges-Armstrong L, Ohlsson C, Perry J, Chambers JC, Kooner JS, Franceschini N, Langenberg C, Hivert M-F, Dastani Z, Richards BJ, Semple R, Frayling TMet al., 2014, Genetic Evidence for a Metabolically Obese, Normal Weight Phenotype That Links Insulin Resistance with Type 2 Diabetes, Hypertension, and Coronary Artery Disease, Publisher: AMER DIABETES ASSOC, Pages: A414-A414, ISSN: 0012-1797

• Author Web Link
• Cite

Flannick J, Thorleifsson G, Beer NL, Jacobs SBR, Grarup N, Burtt NP, Mahajan A, Fuchsberger C, Atzmon G, Benediktsson R, Blangero J, Bowden DW, Brandslund I, Brosnan J, Burslem F, Chambers J, Cho YS, Christensen C, Douglas DA, Duggirala R, Dymek Z, Farjoun Y, Fennell T, Fontanillas P, Forsén T, Gabriel S, Glaser B, Gudbjartsson DF, Hanis C, Hansen T, Hreidarsson AB, Hveem K, Ingelsson E, Isomaa B, Johansson S, Jørgensen T, Jørgensen ME, Kathiresan S, Kong A, Kooner J, Kravic J, Laakso M, Lee J-Y, Lind L, Lindgren CM, Linneberg A, Masson G, Meitinger T, Mohlke KL, Molven A, Morris AP, Potluri S, Rauramaa R, Ribel-Madsen R, Richard A-M, Rolph T, Salomaa V, Segrè AV, Skärstrand H, Steinthorsdottir V, Stringham HM, Sulem P, Tai ES, Teo YY, Teslovich T, Thorsteinsdottir U, Trimmer JK, Tuomi T, Tuomilehto J, Vaziri-Sani F, Voight BF, Wilson JG, Boehnke M, McCarthy MI, Njølstad PR, Pedersen O, Go-T2D Consortium, T2D-GENES Consortium, Groop L, Cox DR, Stefansson K, Altshuler Det al., 2014, Loss-of-function mutations in SLC30A8 protect against type 2 diabetes., Nat Genet, Vol: 46, Pages: 357-363

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.

• Abstract
• Author Web Link
• Cite

Mahajan A, Go MJ, Zhang W, Below JE, Gaulton KJ, Ferreira T, Horikoshi M, Johnson AD, Ng MCY, Prokopenko I, Saleheen D, Wang X, Zeggini E, Abecasis GR, Adair LS, Almgren P, Atalay M, Aung T, Baldassarre D, Balkau B, Bao Y, Barnett AH, Barroso I, Basit A, Been LF, Beilby J, Bell GI, Benediktsson R, Bergman RN, Boehm BO, Boerwinkle E, Bonnycastle LL, Burtt N, Cai Q, Campbell H, Carey J, Cauchi S, Caulfield M, Chan JCN, Chang L-C, Chang T-J, Chang Y-C, Charpentier G, Chen C-H, Chen H, Chen Y-T, Chia K-S, Chidambaram M, Chines PS, Cho NH, Cho YM, Chuang L-M, Collins FS, Cornelis MC, Couper DJ, Crenshaw AT, van Dam RM, Danesh J, Das D, de Faire U, Dedoussis G, Deloukas P, Dimas AS, Dina C, Doney ASF, Donnelly PJ, Dorkhan M, van Duijn C, Dupuis J, Edkins S, Elliott P, Emilsson V, Erbel R, Eriksson JG, Escobedo J, Esko T, Eury E, Florez JC, Fontanillas P, Forouhi NG, Forsen T, Fox C, Fraser RM, Frayling TM, Froguel P, Frossard P, Gao Y, Gertow K, Gieger C, Gigante B, Grallert H, Grant GB, Groop LC, Groves CJ, Grundberg E, Guiducci C, Hamsten A, Han B-G, Hara K, Hassanali N, Hattersley AT, Hayward C, Hedman AK, Herder C, Hofman A, Holmen OL, Hovingh K, Hreidarsson AB, Hu C, Hu FB, Hui J, Humphries SE, Hunt SE, Hunter DJ, Hveem K, Hydrie ZI, Ikegami H, Illig T, Ingelsson E, Islam M, Isomaa B, Jackson AU, Jafar T, James A, Jia W, Joeckel K-H, Jonsson A, Jowett JBM, Kadowaki T, Kang HM, Kanoni S, Kao WHL, Kathiresan S, Kato N, Katulanda P, Keinanen-Kiukaanniemi SM, Kelly AM, Khan H, Khaw K-T, Khor C-C, Kim H-L, Kim S, Kim YJ, Kinnunen L, Klopp N, Kong A, Korpi-Hyovalti E, Kowlessur S, Kraft P, Kravic J, Kristensen MM, Krithika S, Kumar A, Kumate J, Kuusisto J, Kwak SH, Laakso M, Lagou V, Lakka TA, Langenberg C, Langford C, Lawrence R, Leander K, Lee J-M, Lee NR, Li M, Li X, Li Y, Liang J, Liju S, Lim W-Y, Lind L, Lindgren CM, Lindholm E, Liu C-T, Liu JJ, Lobbens S, Long J, Loos RJF, Lu W, Luan J, Lyssenko V, Ma RCW, Maeda S, Maegi R, Mannisto S, Matthews DR, Meigs JB, Melanderet al., 2014, Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility, Nature Genetics, Vol: 46, Pages: 234-244, ISSN: 1061-4036

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

• Abstract
• Publisher Web Link
• Author Web Link
• Open Access Link
• Cite

Williams AL, Jacobs SBR, Moreno-Macias H, Huerta-Chagoya A, Churchhouse C, Marquez-Luna C, Garcia-Ortiz H, Jose Gomez-Vazquez M, Burtt NP, Aguilar-Salinas CA, Gonzalez-Villalpando C, Florez JC, Orozco L, Haiman CA, Tusie-Luna T, Altshuler D, Williams AL, Marquez-Luna C, Huerta-Chagoya A, Ripke S, Jose Gomez-Vazquez M, Manning AK, Moreno-Macias H, Garcia-Ortiz H, Neale B, Burtt NP, Aguilar-Salinas CA, Reich D, Stram DO, Carlos Fernandez-Lopez J, Romero-Hidalgo S, Altshuler D, Florez JC, Tusie-Luna T, Patterson N, Haiman CA, Aguilar-Delfin I, Martinez-Hernandez A, Centeno-Cruz F, Mendoza-Caamal E, Revilla-Monsalve C, Islas-Andrade S, Cordova E, Rodriguez-Arellano E, Soberon X, Orozco L, Florez JC, Gonzalez-Villalpando C, Elena Gonzalez-Villalpando M, Haiman CA, Henderson BE, Monroe K, Wilkens L, Kolonel LN, Le Marchand L, Riba L, Luisa Ordonez-Sanchez M, Rodriguez-Guillen R, Cruz-Bautista I, Rodriguez-Torres M, Liliana Munoz-Hernandez L, Saenz T, Gomez D, Alvirde U, Burtt NP, Onofrio RC, Brodeur WM, Gage D, Murphy J, Franklin J, Mahan S, Ardlie K, Crenshaw AT, Winckler W, Prufer K, Shunkov MV, Sawyer S, Stenzel U, Kelso J, Lek M, Sankararaman S, Williams AL, Patterson N, MacArthur DG, Reich D, Derevianko AP, Paabo S, Jacobs SBR, Churchhouse C, Gopal S, Grammatikos JA, Smith IC, Bullock KH, Deik AA, Souza AL, Pierce KA, Clish CB, Altshuler D, Fennell T, Farjoun Y, Gabriel S, Stram DO, Gross MD, Pereira MA, Seielstad M, Koh W-P, Tai E-S, Flannick J, Fontanillas P, Morris A, Teslovich TM, Burtt NP, Atzmon G, Blangero J, Bowden DW, Chambers J, Cho YS, Duggirala R, Glaser B, Hanis C, Kooner J, Laakso M, Lee J-Y, Tai E-S, Teo YY, Wilson JG, Haiman CA, Henderson BE, Monroe K, Wilkens L, Kolonel LN, Le Marchand L, Puppala S, Farook VS, Thameem F, Abboud HE, DeFronzo RA, Jenkinson CP, Lehman DM, Curran JE, Blangero J, Duggirala R, Burtt NP, Cortes ML, Altshuler D, Florez JC, Haiman CA, Henderson BE, Aguilar-Salinas CA, Gonzalez-Villalpando C, Orozco L, Tusie-Luna Tet al., 2014, Sequence variants in <i>SLC16A11</i> are a common risk factor for type 2 diabetes in Mexico, NATURE, Vol: 506, Pages: 97-+, ISSN: 0028-0836

• Author Web Link
• Cite
• Citations: 61

Dichgans M, Malik R, Koenig IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O'Donnell CJ, Fornage M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J, Bis JC, Peters A, Boncoraglio GB, Maerz W, Meschia JF, Kathiresan S, Ikram MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR, Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, Schunkert Het al., 2014, Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease A Genome-Wide Analysis of Common Variants, STROKE, Vol: 45, Pages: 24-36, ISSN: 0039-2499

• Author Web Link
• Cite
• Citations: 249

Dichgans M, Malik R, Koenig IR, Rosand J, Clarke R, Gretarsdottir S, Mitchell BD, Erdmann J, Kathiresan S, McPherson R, Sudlow C, Reilly MP, Thompson JR, Sharma P, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, Schunkert Het al., 2013, Evidence for a shared genetic determination of Ischemic Stroke And Coronary Artery Disease - a genome-wide analysis, Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E160-E161, ISSN: 0009-7330

• Author Web Link
• Cite

Walker DG, Williams HRT, Bancil AS, Rai P, Pantelidis P, Chambers J, Kooner JS, Sato H, Orchard TRet al., 2013, Ethnicity Differences in Genetic Susceptibility to Ulcerative Colitis: A Comparison of Indian Asians and White Northern Europeans, INFLAMMATORY BOWEL DISEASES, Vol: 19, Pages: 2888-2894, ISSN: 1078-0998

• Author Web Link
• Cite
• Citations: 10

Tan S-T, Rai B, Boustead L, Badii F, Howell N, Frost G, Scott J, Elliott P, Chambers JC, Koner JSet al., 2013, Assessing the Contribution of Dietary Factors to the Increased Prevalence of Insulin Resistance Amongst Uk Indian Asians Compared to Europeans, Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

• Author Web Link
• Cite

Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang H-Y, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkila K, Hyppoenen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikainen L-P, Magnusson PKE, Mangino M, Mihailov E, Montasser ME, Mueller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen A-K, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney ASF, Doering A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen A-L, Hayward C, Hernandez D, Hicks AA, Holm H, Hung Y-J, Illig T, Jones MR, Kaleebu P, Kastelein JJP, Khaw K-T, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimaki T, Lin S-Y, Lindstrom J, Loos RJF, Mach F, McArdle WL, Meisinger C, Mitchell BD, Mueller G, Nagaraja R, Narisu N, Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stancakova A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen Y-DI, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrieres J, Ferrucci L, Freet al., 2013, Common variants associated with plasma triglycerides and risk for coronary artery disease, Nature Genetics, Vol: 45, Pages: 1345-1352, ISSN: 1061-4036

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10−8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

• Abstract
• Publisher Web Link
• Author Web Link
• Open Access Link
• Cite

Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang H-Y, Demirkan A, Den Hertog HM, Do R, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkila K, Hyppoenen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikainen L-P, Magnusson PKE, Mangino M, Mihailov E, Montasser ME, Mueller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen A-K, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney ASF, Doering A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen A-L, Hayward C, Hernandez D, Hicks AA, Holm H, Hung Y-J, Illig T, Jones MR, Kaleebu P, Kastelein JJP, Khaw K-T, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimaki T, Lin S-Y, Lindstrom J, Loos RJF, Mach F, McArdle WL, Meisinger C, Mitchell BD, Mueller G, Nagaraja R, Narisu N, Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stancakova A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen Y-DI, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrieres J, Ferrucci L, Freimer NBet al., 2013, Discovery and refinement of loci associated with lipid levels, Nature Genetics, Vol: 45, Pages: 1274-1283, ISSN: 1061-4036

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

• Abstract
• Publisher Web Link
• Author Web Link
• Open Access Link
• Cite

O'Seaghdha CM, Wu H, Yang Q, Kapur K, Guessous I, Zuber AM, Koettgen A, Stoudmann C, Teumer A, Kutalik Z, Mangino M, Dehghan A, Zhang W, Eiriksdottir G, Li G, Tanaka T, Portas L, Lopez LM, Hayward C, Lohman K, Matsuda K, Padmanabhan S, Firsov D, Sorice R, Ulivi S, Brockhaus AC, Kleber ME, Mahajan A, Ernst FD, Gudnason V, Launer LJ, Mace A, Boerwinckle E, Arking DE, Tanikawa C, Nakamura Y, Brown MJ, Gaspoz J-M, Theler J-M, Siscovick DS, Psaty BM, Bergmann S, Vollenweider P, Vitart V, Wright AF, Zemunik T, Boban M, Kolcic I, Navarro P, Brown EM, Estrada K, Ding J, Harris TB, Bandinelli S, Hernandez D, Singleton AB, Girotto G, Ruggiero D, d'Adamo AP, Robino A, Meitinger T, Meisinger C, Davies G, Starr JM, Chambers JC, Boehm BO, Winkelmann BR, Huang J, Murgia F, Wild SH, Campbell H, Morris AP, Franco OH, Hofman A, Uitterlinden AG, Rivadeneira F, Voelker U, Hannemann A, Biffar R, Hoffmann W, Shin S-Y, Lescuyer P, Henry H, Schurmann C, Munroe PB, Gasparini P, Pirastu N, Ciullo M, Gieger C, Maerz W, Lind L, Spector TD, Smith AV, Rudan I, Wilson JF, Polasek O, Deary IJ, Pirastu M, Ferrucci L, Liu Y, Kestenbaum B, Kooner JS, Witteman JCM, Nauck M, Kao WHL, Wallaschofski H, Bonny O, Fox CS, Bochud Met al., 2013, Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations, PLoS Genetics, Vol: 9, Pages: 1-13, ISSN: 1553-7390

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

• Abstract
• Publisher Web Link
• Author Web Link
• Open Access Link
• Cite

Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD, Teumer A, Reiner AP, Folkersen L, Basu S, Rudnicka AR, Trompet S, Malarstig A, Baumert J, Bis JC, Guo X, Hottenga JJ, Shin S-Y, Lopez LM, Lahti J, Tanaka T, Yanek LR, Oudot-Mellakh T, Wilson JF, Navarro P, Huffman JE, Zemunik T, Redline S, Mehra R, Pulanic D, Rudan I, Wright AF, Kolcic I, Polasek O, Wild SH, Campbell H, Curb JD, Wallace R, Liu S, Eaton CB, Becker DM, Becker LC, Bandinelli S, Raikkonen K, Widen E, Palotie A, Fornage M, Green D, Gross M, Davies G, Harris SE, Liewald DC, Starr JM, Williams FMK, Grant PJ, Spector TD, Strawbridge RJ, Silveira A, Sennblad B, Rivadeneira F, Uitterlinden AG, Franco OH, Hofman A, van Dongen J, Willemsen G, Boomsma DI, Yao J, Jenny NS, Haritunians T, McKnight B, Lumley T, Taylor KD, Rotter JI, Psaty BM, Peters A, Gieger C, Illig T, Grotevendt A, Homuth G, Voelzke H, Kocher T, Goel A, Franzosi MG, Seedorf U, Clarke R, Steri M, Tarasov KV, Sanna S, Schlessinger D, Stott DJ, Sattar N, Buckley BM, Rumley A, Lowe GD, McArdle WL, Chen M-H, Tofler GH, Song J, Boerwinkle E, Folsom AR, Rose LM, Franco-Cereceda A, Teichert M, Ikram MA, Mosley TH, Bevan S, Dichgans M, Rothwell PM, Sudlow CLM, Hopewell JC, Chambers JC, Saleheen D, Kooner JS, Danesh J, Nelson CP, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Morange P-E, Ferrucci L, Eriksson JG, Jacobs D, Deary IJ, Soranzo N, Witteman JCM, de Geus EJC, Tracy RP, Hayward C, Koenig W, Cucca F, Jukema JW, Eriksson P, Seshadri S, Markus HS, Watkins H, Samani NJ, Wallaschofski H, Smith NL, Tregouet D, Ridker PM, Tang W, Strachan DP, Hamsten A, O'Donnell CJet al., 2013, Multiethnic Meta-Analysis of Genome-Wide Association Studies in &gt; 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease, CIRCULATION, Vol: 128, Pages: 1310-1324, ISSN: 0009-7322

• Author Web Link
• Cite
• Citations: 113

van Meurs JBJ, Pare G, Schwartz SM, Hazra A, Tanaka T, Vermeulen SH, Cotlarciuc I, Yuan X, Malarstig A, Bandinelli S, Bis JC, Morn H, Brown MJ, Chen C, Chen Y-D, Clarke RJ, Dehghan A, Erdmann J, Ferrucci L, Hamsten A, Hofman A, Hunten DJ, Goel A, Johnson AD, Kathiresan S, Kampman E, Kiel DP, Kiemeney LA, Chambers JC, Kraft P, Lindemans J, McKnight B, Nelson CP, O'Donnell CJ, Psaty BM, Ridken PM, Rivadeneira F, Rose LM, Seedoif U, Siscovick DS, Schunkert H, Selhub J, Ueland PM, Vollenweiden P, Waeben G, Waterworth DM, Watkins H, Witteman JCM, den Heijen M, Jacques P, Uitterlinden AG, Koonet JS, Rader DJ, Reilly MP, Moose V, Chasman DI, Samani NJ, Ahmadi KRet al., 2013, Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 98, Pages: 668-676, ISSN: 0002-9165

• Author Web Link
• Cite
• Citations: 143

Sabharwal S, Patel V, Nijjer SS, Kirresh A, Darzi A, Chambers JC, Malik I, Kooner JS, Athanasiou Tet al., 2013, Guidelines in cardiac clinical practice: evaluation of their methodological quality using the AGREE II instrument, JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, Vol: 106, Pages: 315-322, ISSN: 0141-0768

• Author Web Link
• Cite
• Citations: 33

Paul DS, Albers CA, Rendon A, Voss K, Stephens J, van der Harst P, Chambers JC, Soranzo N, Ouwehand WH, Deloukas Pet al., 2013, Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci, GENOME RESEARCH, Vol: 23, Pages: 1130-1141, ISSN: 1088-9051

• Author Web Link
• Cite
• Citations: 30

Paul D, Albers CA, Rendon A, Voss K, Stephens J, Van der Harst P, Chambers JC, Soranzo N, Ouwehand WH, Deloukas Pet al., 2013, The epigenetic landscape of platelet and red blood cell traits, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 349-349, ISSN: 1538-7933

• Author Web Link
• Cite

Wang X, Chua H-X, Chen P, Ong RT-H, Sim X, Zhang W, Takeuchi F, Liu X, Khor C-C, Tay W-T, Cheng C-Y, Suo C, Liu J, Aung T, Chia K-S, Kooner JS, Chambers JC, Wong T-Y, Tai E-S, Kato N, Teo Y-Yet al., 2013, Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 2303-2311, ISSN: 0964-6906

• Author Web Link
• Cite
• Citations: 52

den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM, Nolte IM, Segre AV, Holm H, Handsaker RE, Westra H-J, Johnson T, Isaacs A, Yang J, Lundby A, Zhao JH, Kim YJ, Go MJ, Almgren P, Bochud M, Boucher G, Cornelis MC, Gudbjartsson D, Hadley D, van der Harst P, Hayward C, den Heijer M, Igl W, Jackson AU, Kutalik Z, Luan J, Kemp JP, Kristiansson K, Ladenvall C, Lorentzon M, Montasser ME, Njajou OT, O'Reilly PF, Padmanabhan S, Pourcain BS, Rankinen T, Salo P, Tanaka T, Timpson NJ, Vitart V, Waite L, Wheeler W, Zhang W, Draisma HHM, Feitosa MF, Kerr KF, Lind PA, Mihailov E, Onland-Moret NC, Song C, Weedon MN, Xie W, Yengo L, Absher D, Albert CM, Alonso A, Arking DE, de Bakker PIW, Balkau B, Barlassina C, Benaglio P, Bis JC, Bouatia-Naji N, Brage S, Chanock SJ, Chines PS, Chung M, Darbar D, Dina C, Doerr M, Elliott P, Felix SB, Fischer K, Fuchsberger C, de Geus EJC, Goyette P, Gudnason V, Harris TB, Hartikainen A-L, Havulinna AS, Heckbert SR, Hicks AA, Hofman A, Holewijn S, Hoogstra-Berends F, Hottenga J-J, Jensen MK, Johansson A, Junttila J, Kaeaeb S, Kanon B, Ketkar S, Khaw K-T, Knowles JW, Kooner AS, Kors JA, Kumari M, Milani L, Laiho P, Lakatta EG, Langenberg C, Leusink M, Liu Y, Luben RN, Lunetta KL, Lynch SN, Markus MRP, Marques-Vidal P, Leach IM, McArdle WL, McCarroll SA, Medland SE, Miller KA, Montgomery GW, Morrison AC, Mueller-Nurasyid M, Navarro P, Nelis M, O'Connell JR, O'Donnell CJ, Ong KK, Newman AB, Peters A, Polasek O, Pouta A, Pramstaller PP, Psaty BM, Rao DC, Ring SM, Rossin EJ, Rudan D, Sanna S, Scott RA, Sehmi JS, Sharp S, Shin JT, Singleton AB, Smith AV, Soranzo N, Spector TD, Stewart C, Stringham HM, Tarasov KV, Uitterlinden AG, Vandenput L, Hwang S-J, Whitfield JB, Wijmenga C, Wild SH, Willemsen G, Wilson JF, Witteman JCM, Wong A, Wong Q, Jamshidi Y, Zitting P, Boer JMA, Boomsma DI, Borecki IB, van Duijn CM, Ekelund U, Forouhi NG, Froguel P, Hingorani A, Ingelsson E, Kivimaki M, Kronmal RA, Kuh D, Lind L, Martin NG, Oostra BA, Pedersenet al., 2013, Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders, NATURE GENETICS, Vol: 45, Pages: 621-+, ISSN: 1061-4036

• Author Web Link
• Cite
• Citations: 228

Saxena R, Saleheen D, Been LF, Garavito ML, Braun T, Bjonnes A, Young R, Ho WK, Rasheed A, Frossard P, Sim X, Hassanali N, Radha V, Chidambaram M, Liju S, Rees SD, Ng DP-K, Wong T-Y, Yamauchi T, Hara K, Tanaka Y, Hirose H, McCarthy MI, Morris AP, Basit A, Barnett AH, Katulanda P, Matthews D, Mohan V, Wander GS, Singh JR, Mehra NK, Ralhan S, Kamboh MI, Mulvihill JJ, Maegawa H, Tobe K, Maeda S, Cho YS, Tai ES, Kelly MA, Chambers JC, Kooner JS, Kadowaki T, Deloukas P, Rader DJ, Danesh J, Sanghera DKet al., 2013, Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India, Diabetes, Vol: 62, Pages: 1746-1755, ISSN: 0012-1797

We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10−3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10−4) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10−8) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10−3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10−4) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10−5 to < 10−7), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.

• Abstract
• Publisher Web Link
• Author Web Link
• Open Access Link
• Cite

Chahal NS, Lim TK, Jain P, Chambers JC, Kooner JS, Senior Ret al., 2013, The increased prevalence of left ventricular hypertrophy and concentric remodeling in UK Indian Asians compared with European Whites, JOURNAL OF HUMAN HYPERTENSION, Vol: 27, Pages: 288-293, ISSN: 0950-9240

• Author Web Link
• Cite
• Citations: 6

Mughal SA, Chambers JC, Kelly MA, Ellard S, Kooner JS, McCarthy MI, Owen KRet al., 2013, Evaluation of high sensitivity C-reactive protein as a screening tool for detecting young South Asians with maturity-onset diabetes of the young due to <i>HNF1A</i> mutations, DIABETIC MEDICINE, Vol: 30, Pages: 61-61, ISSN: 0742-3071

• Author Web Link
• Cite

Koettgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, Pistis G, Ruggiero D, O'Seaghdha CM, Haller T, Yang Q, Tanaka T, Johnson AD, Kutalik Z, Smith AV, Shi J, Struchalin M, Middelberg RPS, Brown MJ, Gaffo AL, Pirastu N, Li G, Hayward C, Zemunik T, Huffman J, Yengo L, Zhao JH, Demirkan A, Feitosa MF, Liu X, Malerba G, Lopez LM, van der Harst P, Li X, Kleber ME, Hicks AA, Nolte IM, Johansson A, Murgia F, Wild SH, Bakker SJL, Peden JF, Dehghan A, Steri M, Tenesa A, Lagou V, Salo P, Mangino M, Rose LM, Lehtimaki T, Woodward OM, Okada Y, Tin A, Mueller C, Oldmeadow C, Putku M, Czamara D, Kraft P, Frogheri L, Thun GA, Grotevendt A, Gislason GK, Harris TB, Launer LJ, McArdle P, Shuldiner AR, Boerwinkle E, Coresh J, Schmidt H, Schallert M, Martin NG, Montgomery GW, Kubo M, Nakamura Y, Tanaka T, Munroe PB, Samani NJ, Jacobs DR, Liu K, D'Adamo P, Ulivi S, Rotter JI, Psaty BM, Vollenweider P, Waeber G, Campbell S, Devuyst O, Navarro P, Kolcic I, Hastie N, Balkau B, Froguel P, Esko T, Salumets A, Khaw KT, Langenberg C, Wareham NJ, Isaacs A, Kraja A, Zhang Q, Wild PS, Scott RJ, Holliday EG, Org E, Viigimaa M, Bandinelli S, Metter JE, Lupo A, Trabetti E, Sorice R, Doering A, Lattka E, Strauch K, Theis F, Waldenberger M, Wichmann H-E, Davies G, Gow AJ, Bruinenberg M, Stolk RP, Kooner JS, Zhang W, Winkelmann BR, Boehm BO, Lucae S, Penninx BW, Smit JH, Curhan G, Mudgal P, Plenge RM, Portas L, Persico I, Kirin M, Wilson JF, Leach IM, van Gilst WH, Goel A, Ongen H, Hofman A, Rivadeneira F, Uitterlinden AG, Imboden M, von Eckardstein A, Cucca F, Nagaraja R, Piras MG, Nauck M, Schurmann C, Budde K, Ernst F, Farrington SM, Theodoratou E, Prokopenko I, Stumvoll M, Jula A, Perola M, Salomaa V, Shin S-Y, Spector TD, Sala C, Ridker PM, Kaehoenen M, Viikari J, Hengstenberg C, Nelson CP, Meschia JF, Nalls MA, Sharma P, Singleton AB, Kamatani N, Zeller T, Burnier M, Attia J, Laan M, Klopp N, Hillege HL, Kloiber S, Choi H, Pirastu M, Tore S, Probst-Hensch NM, Voelzke H, Gudnasonet al., 2013, Genome-wide association analyses identify 18 new loci associated with serum urate concentrations, NATURE GENETICS, Vol: 45, Pages: 145-154, ISSN: 1061-4036

• Author Web Link
• Cite
• Citations: 561