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3. Author Correction: Genetic analysis of over half a million people characterises C-reactive protein loci (Nature Communications, (2022), 13, 1, (2198), 10.1038/s41467-022-29650-5)

Author

Said, S, Pazoki, R, Karhunen, V, Võsa, U, Ligthart, S, Bodinier, B, Koskeridis, F, Welsh, P, Alizadeh, BZ, Chasman, DI, Sattar, N, Chadeau-Hyam, M, Evangelou, E, Jarvelin, MR, Elliott, P, Tzoulaki, I, and Dehghan, A

Abstract

Copyright © The Author(s) 2022. The original version of this article contained an error in the section “Data Availability”, which incorrectly read ‘The derived CRP GWAS meta-analysis summary statistics generated in this study has been deposited in the GWAS catalogue under accession code GCST00186 (https://www.ebi.ac.uk/gwas/)’. The correct version states ‘GCST90029070’ in place of ‘GCST00186’ and states “have” in place of “has”. This has been corrected in both the PDF and HTML versions of the Article.

Published
2022

5. Genetic analysis of over half a million people characterises C-reactive protein loci

Author

Said, S. (Saredo), Pazoki, R. (Raha), Karhunen, V. (Ville), Võsa, U. (Urmo), Ligthart, S. (Symen), Bodinier, B. (Barbara), Koskeridis, F. (Fotios), Welsh, P. (Paul), Alizadeh, B. Z. (Behrooz Z.), Chasman, D. I. (Daniel I.), Sattar, N. (Naveed), Chadeau-Hyam, M. (Marc), Evangelou, E. (Evangelos), Järvelin, M.-R. (Marjo-Riitta), Elliott, P. (Paul), Tzoulaki, I. (Ioanna), Dehghan, A. (Abbas), Said, S. (Saredo), Pazoki, R. (Raha), Karhunen, V. (Ville), Võsa, U. (Urmo), Ligthart, S. (Symen), Bodinier, B. (Barbara), Koskeridis, F. (Fotios), Welsh, P. (Paul), Alizadeh, B. Z. (Behrooz Z.), Chasman, D. I. (Daniel I.), Sattar, N. (Naveed), Chadeau-Hyam, M. (Marc), Evangelou, E. (Evangelos), Järvelin, M.-R. (Marjo-Riitta), Elliott, P. (Paul), Tzoulaki, I. (Ioanna), and Dehghan, A. (Abbas)

Abstract

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

Published
2022

8. Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality among 398 628 Individuals in UK Biobank

Author

Elliott, P, Muller, DC, Schneider-Luftman, D, Pazoki, R, Evangelou, E, Dehghan, A, Neal, B, Tzoulaki, I, Elliott, P, Muller, DC, Schneider-Luftman, D, Pazoki, R, Evangelou, E, Dehghan, A, Neal, B, and Tzoulaki, I

Abstract

We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.

Published
2020

9. Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Author

Robinson, O. (Oliver), Chadeau Hyam, M. (Marc), Karaman, I. (Ibrahim), Climaco Pinto, R. (Rui), Ala-Korpela, M. (Mika), Handakas, E. (Evangelos), Fiorito, G. (Giovanni), Gao, H. (He), Heard, A. (Andy), Jarvelin, M. (Marjo‐Riitta), Lewis, M. (Matthew), Pazoki, R. (Raha), Polidoro, S. (Silvia), Tzoulaki, I. (Ioanna), Wielscher, M. (Matthias), Elliott, P. (Paul), Vineis, P. (Paolo), Robinson, O. (Oliver), Chadeau Hyam, M. (Marc), Karaman, I. (Ibrahim), Climaco Pinto, R. (Rui), Ala-Korpela, M. (Mika), Handakas, E. (Evangelos), Fiorito, G. (Giovanni), Gao, H. (He), Heard, A. (Andy), Jarvelin, M. (Marjo‐Riitta), Lewis, M. (Matthew), Pazoki, R. (Raha), Polidoro, S. (Silvia), Tzoulaki, I. (Ioanna), Wielscher, M. (Matthias), Elliott, P. (Paul), and Vineis, P. (Paolo)

Abstract

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = 0.86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.

Published
2020

11. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps (Nature Genetics, (2016), 48, 11, (1303-1312), 10.1038/ng.3668)

Author

Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., Soranzo, N., Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., and Soranzo, N.

Subjects
Author correction
Abstract

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

Published
2018

12. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (Nature Genetics, (2018), 50, 10, (1412-1425), 10.1038/s41588-018-0205-x)

Author

Evangelou E., Warren H. R., Mosen-Ansorena D., Mifsud B., Pazoki R., Gao H., Ntritsos G., Dimou N., Cabrera C. P., Karaman I., Ng F. L., Evangelou M., Witkowska K., Tzanis E., Hellwege J. N., Giri A., Velez Edwards D. R., Sun Y. V., Cho K., Gaziano J. M., Wilson P. W. F., Tsao P. S., Kovesdy C. P., Esko T., Magi R., Milani L., Almgren P., Boutin T., Debette S., Ding J., Giulianini F., Holliday E. G., Jackson A. U., Li-Gao R., Lin W. -Y., Luan J., Mangino M., Oldmeadow C., Prins B. P., Qian Y., Sargurupremraj M., Shah N., Surendran P., Theriault S., Verweij N., Willems S. M., Zhao J. -H., Amouyel P., Connell J., de Mutsert R., Doney A. S. F., Farrall M., Menni C., Morris A. D., Noordam R., Pare G., Poulter N. R., Shields D. C., Stanton A., Thom S., Abecasis G., Amin N., Arking D. E., Ayers K. L., Barbieri C. M., Batini C., Bis J. C., Blake T., Bochud M., Boehnke M., Boerwinkle E., Boomsma D. I., Bottinger E. P., Braund P. S., Brumat M., Campbell A., Campbell H., Chakravarti A., Chambers J. C., Chauhan G., Ciullo M., Cocca M., Collins F., Cordell H. J., Davies G., de Borst M. H., de Geus E. J., Deary I. J., Deelen J., Del Greco M F., Demirkale C. Y., Dorr M., Ehret G. B., Elosua R., Enroth S., Erzurumluoglu A. M., Ferreira T., Franberg M., Franco O. H., Gandin I., Gasparini P., Giedraitis V., Gieger C., Girotto G., Goel A., Gow A. J., Gudnason V., Guo X., Gyllensten U., Hamsten A., Harris T. B., Harris S. E., Hartman C. A., Havulinna A. S., Hicks A. A., Hofer E., Hofman A., Hottenga J. -J., Huffman J. E., Hwang S. -J., Ingelsson E., James A., Jansen R., Jarvelin M. -R., Joehanes R., Johansson A., Johnson A. D., Joshi P. K., Jousilahti P., Jukema J. W., Jula A., Kahonen M., Kathiresan S., Keavney B. D., Khaw K. -T., Knekt P., Knight J., Kolcic I., Kooner J. S., Koskinen S., Kristiansson K., Kutalik Z., Laan M., Larson M., Launer L. J., Lehne B., Lehtimaki T., Liewald D. C. M., Lin L., Lind L., Lindgren C. M., Liu Y. M., Loos R. J. F., Lopez L. M., Lu Y., Lyytikainen L. -P., Mahajan A., Mamasoula C., Marrugat J., Marten J., Milaneschi Y., Morgan A., Morris A. P., Morrison A. C., Munson P. J., Nalls M. A., Nandakumar P., Nelson C. P., Niiranen T., Nolte I. M., Nutile T., Oldehinkel A. J., Oostra B. A., O'Reilly P. F., Org E., Padmanabhan S., Palmas W., Palotie A., Pattie A., Penninx B. W. J. H., Perola M., Peters A., Polasek O., Pramstaller P. P., Nguyen Q. T., Raitakari O. T., Ren M., Rettig R., Rice K., Ridker P. M., Ried J. S., Riese H., Ripatti S., Robino A., Rose L. M., Rotter J. I., Rudan I., Ruggiero D., Saba Y., Sala C. F., Salomaa V., Samani N. J., Sarin A. -P., Schmidt R., Schmidt H., Shrine N., Siscovick D., Smith A. V., Snieder H., Sober S., Sorice R., Starr J. M., Stott D. J., Strachan D. P., Strawbridge R. J., Sundstrom J., Swertz M. A., Taylor K. D., Teumer A., Tobin M. D., Tomaszewski M., Toniolo D., Traglia M., Trompet S., Tuomilehto J., Tzourio C., Uitterlinden A. G., Vaez A., van der Most P. J., van Duijn C. M., Vergnaud A. -C., Verwoert G. C., Vitart V., Volker U., Vollenweider P., Vuckovic D., Watkins H., Wild S. H., Willemsen G., Wilson J. F., Wright A. F., Yao J., Zemunik T., Zhang W., Attia J. R., Butterworth A. S., Chasman D. I., Conen D., Cucca F., Danesh J., Hayward C., Howson J. M. M., Laakso M., Lakatta E. G., Langenberg C., Melander O., Mook-Kanamori D. O., Palmer C. N. A., Risch L., Scott R. A., Scott R. J., Sever P., Spector T. D., van der Harst P., Wareham N. J., Zeggini E., Levy D., Munroe P. B., Newton-Cheh C., Brown M. J., Metspalu A., Hung A. M., O'Donnell C. J., Edwards T. L., Psaty B. M., Tzoulaki I., Barnes M. R., Wain L. V., Elliott P., Caulfield M. J., Evangelou, E., Warren, H. R., Mosen-Ansorena, D., Mifsud, B., Pazoki, R., Gao, H., Ntritsos, G., Dimou, N., Cabrera, C. P., Karaman, I., Ng, F. L., Evangelou, M., Witkowska, K., Tzanis, E., Hellwege, J. N., Giri, A., Velez Edwards, D. R., Sun, Y. V., Cho, K., Gaziano, J. M., Wilson, P. W. F., Tsao, P. S., Kovesdy, C. P., Esko, T., Magi, R., Milani, L., Almgren, P., Boutin, T., Debette, S., Ding, J., Giulianini, F., Holliday, E. G., Jackson, A. U., Li-Gao, R., Lin, W. -Y., Luan, J., Mangino, M., Oldmeadow, C., Prins, B. P., Qian, Y., Sargurupremraj, M., Shah, N., Surendran, P., Theriault, S., Verweij, N., Willems, S. M., Zhao, J. -H., Amouyel, P., Connell, J., de Mutsert, R., Doney, A. S. F., Farrall, M., Menni, C., Morris, A. D., Noordam, R., Pare, G., Poulter, N. R., Shields, D. C., Stanton, A., Thom, S., Abecasis, G., Amin, N., Arking, D. E., Ayers, K. L., Barbieri, C. M., Batini, C., Bis, J. C., Blake, T., Bochud, M., Boehnke, M., Boerwinkle, E., Boomsma, D. I., Bottinger, E. P., Braund, P. S., Brumat, M., Campbell, A., Campbell, H., Chakravarti, A., Chambers, J. C., Chauhan, G., Ciullo, M., Cocca, M., Collins, F., Cordell, H. J., Davies, G., de Borst, M. H., de Geus, E. J., Deary, I. J., Deelen, J., Del Greco M, F., Demirkale, C. Y., Dorr, M., Ehret, G. B., Elosua, R., Enroth, S., Erzurumluoglu, A. M., Ferreira, T., Franberg, M., Franco, O. H., Gandin, I., Gasparini, P., Giedraitis, V., Gieger, C., Girotto, G., Goel, A., Gow, A. J., Gudnason, V., Guo, X., Gyllensten, U., Hamsten, A., Harris, T. B., Harris, S. E., Hartman, C. A., Havulinna, A. S., Hicks, A. A., Hofer, E., Hofman, A., Hottenga, J. -J., Huffman, J. E., Hwang, S. -J., Ingelsson, E., James, A., Jansen, R., Jarvelin, M. -R., Joehanes, R., Johansson, A., Johnson, A. D., Joshi, P. K., Jousilahti, P., Jukema, J. W., Jula, A., Kahonen, M., Kathiresan, S., Keavney, B. D., Khaw, K. -T., Knekt, P., Knight, J., Kolcic, I., Kooner, J. S., Koskinen, S., Kristiansson, K., Kutalik, Z., Laan, M., Larson, M., Launer, L. J., Lehne, B., Lehtimaki, T., Liewald, D. C. M., Lin, L., Lind, L., Lindgren, C. M., Liu, Y. M., Loos, R. J. F., Lopez, L. M., Lu, Y., Lyytikainen, L. -P., Mahajan, A., Mamasoula, C., Marrugat, J., Marten, J., Milaneschi, Y., Morgan, A., Morris, A. P., Morrison, A. C., Munson, P. J., Nalls, M. A., Nandakumar, P., Nelson, C. P., Niiranen, T., Nolte, I. M., Nutile, T., Oldehinkel, A. J., Oostra, B. A., O'Reilly, P. F., Org, E., Padmanabhan, S., Palmas, W., Palotie, A., Pattie, A., Penninx, B. W. J. H., Perola, M., Peters, A., Polasek, O., Pramstaller, P. P., Nguyen, Q. T., Raitakari, O. T., Ren, M., Rettig, R., Rice, K., Ridker, P. M., Ried, J. S., Riese, H., Ripatti, S., Robino, A., Rose, L. M., Rotter, J. I., Rudan, I., Ruggiero, D., Saba, Y., Sala, C. F., Salomaa, V., Samani, N. J., Sarin, A. -P., Schmidt, R., Schmidt, H., Shrine, N., Siscovick, D., Smith, A. V., Snieder, H., Sober, S., Sorice, R., Starr, J. M., Stott, D. J., Strachan, D. P., Strawbridge, R. J., Sundstrom, J., Swertz, M. A., Taylor, K. D., Teumer, A., Tobin, M. D., Tomaszewski, M., Toniolo, D., Traglia, M., Trompet, S., Tuomilehto, J., Tzourio, C., Uitterlinden, A. G., Vaez, A., van der Most, P. J., van Duijn, C. M., Vergnaud, A. -C., Verwoert, G. C., Vitart, V., Volker, U., Vollenweider, P., Vuckovic, D., Watkins, H., Wild, S. H., Willemsen, G., Wilson, J. F., Wright, A. F., Yao, J., Zemunik, T., Zhang, W., Attia, J. R., Butterworth, A. S., Chasman, D. I., Conen, D., Cucca, F., Danesh, J., Hayward, C., Howson, J. M. M., Laakso, M., Lakatta, E. G., Langenberg, C., Melander, O., Mook-Kanamori, D. O., Palmer, C. N. A., Risch, L., Scott, R. A., Scott, R. J., Sever, P., Spector, T. D., van der Harst, P., Wareham, N. J., Zeggini, E., Levy, D., Munroe, P. B., Newton-Cheh, C., Brown, M. J., Metspalu, A., Hung, A. M., O'Donnell, C. J., Edwards, T. L., Psaty, B. M., Tzoulaki, I., Barnes, M. R., Wain, L. V., Elliott, P., and Caulfield, M. J.

Subjects
Blood pressure, genetic analysis
Abstract

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Published
2018

13. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Bohmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kahonen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikainen, L.P., Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumare, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Raikkonen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Published
2019

14. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S. E., TRAMPUSH, J. W., LUCIANO, M., HILL, W. D., HAGENAARS, S. P., RITCHIE, S. J., MARIONI, R. E., FAWNS-RITCHIE, C., LIEWALD, D. C. M., OKELY, J. A., AHOLA-OLLI, A. V., BARNES, C. L. K., Bertram, L., BIS, J. C., BURDICK, K. E., CHRISTOFOROU, A., DEROSSE, P., Djurovic, S., ESPESETH, T., GIAKOUMAKI, S., GIDDALURU, S., GUSTAVSON, D. E., Hayward, C., Hofer, E., KARLSSON, R., KNOWLES, E., Lahti, J., Leber, M., MATHER, K. A., Melle, I., Morris, D., OLDMEADOW, C., PALVIAINEN, T., PAYTON, A., PAZOKI, R., PETROVIC, K., Reynolds, C. A., SARGURUPREMRAJ, M., Scholz, M., Smith, J. A., SMITH, A. V., TERZIKHAN, N., THALAMUTHU, A., TROMPET, S., VAN DER LEE, S. J., WARE, E. B., WINDHAM, B. G., WRIGHT, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., ANDREASSEN, O. A., ARMSTRONG, N. J., ASSAREH, A. A., ATTIA, J. R., ATTIX, D., AVRAMOPOULOS, D., BENNETT, D. A., BOHMER, A. C., BOYLE, P. A., BRODATY, H., Campbell, H., CANNON, T. D., CIRULLI, E. T., CONGDON, E., CONLEY, E. D., CORLEY, J., COX, S. R., DALE, A. M., DEHGHAN, A., Dick, D., Dickinson, D., ERIKSSON, J. G., EVANGELOU, E., FAUL, J. D., Ford, I., FREIMER, N. A., Gao, H., Giegling, I., GILLESPIE, N. A., GORDON, S. D., GOTTESMAN, R. F., GRISWOLD, M. E., GUDNASON, V., HARRIS, T. B., HARTMANN, A. M., Hatzimanolis, A., Heiss, G., HOLLIDAY, E. G., Joshi, P. K., KAHONEN, M., KARDIA, S. L. R., KARLSSON, I., KLEINEIDAM, L., KNOPMAN, D. S., KOCHAN, N. A., Konte, B., KWOK, J. B., LE HELLARD, S., Lee, T., LEHTIMAKI, T., Li, S. C., Lill, C. M., Liu, T., KOINI, M., London, E., LONGSTRETH, W. T., Jr., LOPEZ, O. L., LOUKOLA, A., LUCK, T., LUNDERVOLD, A. J., LUNDQUIST, A., LYYTIKAINEN, L. P., Martin, N. G., MONTGOMERY, G. W., MURRAY, A. D., NEED, A. C., NOORDAM, R., Nyberg, L., OLLIER, W., PAPENBERG, G., PATTIE, A., POLASEK, O., POLDRACK, R. A., PSATY, B. M., REPPERMUND, S., RIEDEL-HELLER, S. G., ROSE, R. J., ROTTER, J. I., ROUSSOS, P., ROVIO, S. P., SABA, Y., SABB, F. W., SACHDEV, P. S., SATIZABAL, C. L., Schmid, M., Scott, R. J., SCULT, M. A., SIMINO, J., SLAGBOOM, P. E., SMYRNIS, N., Soumare, A., Stefanis, N. C., STOTT, D. J., STRAUB, R. E., SUNDET, K., Taylor, A. M., TAYLOR, K. D., TZOULAKI, I., Tzourio, C., Uitterlinden, A., Vitart, V., VOINESKOS, A. N., Kaprio, J., Wagner, M., Wagner, H., WEINHOLD, L., WEN, K. H., WIDEN, E., Yang, Q., Zhao, W., ADAMS, H. H. H., ARKING, D. E., Bilder, R. M., BITSIOS, P., BOERWINKLE, E., CHIBA-FALEK, O., Corvin, A., DE JAGER, P. L., Debette, S., Donohoe, G., Elliott, P., FITZPATRICK, A. L., Gill, M., GLAHN, D. C., HAGG, S., HANSELL, N. K., HARIRI, A. R., Ikram, M. A., JUKEMA, J. W., VUOKSIMAA, E., KELLER, M. C., KREMEN, W. S., LAUNER, L., LINDENBERGER, U., Palotie, A., PEDERSEN, N. L., PENDLETON, N., PORTEOUS, D. J., RAIKKONEN, K., RAITAKARI, O. T., Ramirez, A., REINVANG, I., RUDAN, I., DAN, Rujescu, Schmidt, R., Schmidt, H., SCHOFIELD, P. W., STARR, J. M., STEEN, V. M., TROLLOR, J. N., TURNER, S. T., VAN DUIJN, C. M., VILLRINGER, A., WEINBERGER, D. R., WEIR, D. R., WILSON, J. F., Malhotra, A., MCINTOSH, A. M., GALE, C. R., SESHADRI, S., MOSLEY, T. H., Jr., BRESSLER, J., Lencz, T., DEARY, I. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019

15. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. Uitterlinden, A. Vitart, V. Voineskos, A.N. Kaprio, J. Wagner, M. Wagner, H. Weinhold, L. Wen, K.H. Widen, E. Yang, Q. Zhao, W. Adams, H.H.H. Arking, D.E. Bilder, R.M. Bitsios, P. Boerwinkle, E. Chiba-Falek, O. Corvin, A. De Jager, P.L. Debette, S. Donohoe, G. Elliott, P. Fitzpatrick, A.L. Gill, M. Glahn, D.C. Hägg, S. Hansell, N.K. Hariri, A.R. Ikram, M.K. Jukema, J.W. Vuoksimaa, E. Keller, M.C. Kremen, W.S. Launer, L. Lindenberger, U. Palotie, A. Pedersen, N.L. Pendleton, N. Porteous, D.J. Räikkönen, K. Raitakari, O.T. Ramirez, A. Reinvang, I. Rudan, I. Dan Rujescu Schmidt, R. Schmidt, H. Schofield, P.W. Schofield, P.R. Starr, J.M. Steen, V.M. Trollor, J.N. Turner, S.T. Van Duijn, C.M. Villringer, A. Weinberger, D.R. Weir, D.R. Wilson, J.F. Malhotra, A. McIntosh, A.M. Gale, C.R. Seshadri, S. Mosley, T.H., Jr. Bressler, J. Lencz, T. Deary, I.J.

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. © 2019, The Author(s).

Published
2019

16. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, Derosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, Van Der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, and Brodaty, H

Abstract

© 2018 The Author(s). General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

17. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, and Kleineidam, L

Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019

18. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), Morrison, A.C. (Alanna), Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. 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(Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), and Morrison, A.C. (Alanna)

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019
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19. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author

Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), and Loos, R.J.F. (Ruth)

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 l

Published
2019
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20. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author

Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, Loos, RJF, Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, and Loos, RJF

Published
2019

21. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

Author

Evangelou, E, Warren, HR, Mosen-Ansorena, D, Mifsud, B, Pazoki, R, Gao, H, Ntritsos, G, Dimou, N, Cabrera, CP, Karaman, I, Fu, LN, Evangelou, M, Witkowska, K, Tzanis, E, Hellwege, JN, Giri, A, Edwards, DRV, Sun, YV, Cho, K, Gaziano, JM, Wilson, PWF, Tsao, PS, Kovesdy, CP, Esko, T, Magi, R, Milani, L, Almgren, P, Boutin, T, Debette, S, Ding, J, Giulianini, F, Holliday, EG, Jackson, AU, Li-Gao, R, Lin, W-Y, Luan, J, Mangino, M, Oldmeadow, C, Prins, BP, Qian, Y, Sargurupremraj, M, Shah, N, Surendran, P, Theriault, S, Verweij, N, Willems, SM, Zhao, J-H, Amouyel, P, Connell, J, De Mutsert, R, Doney, ASF, Farrall, M, Menni, C, Morris, AD, Noordam, R, Pare, G, Poulter, NR, Shields, DC, Stanton, A, Thom, S, Abecasis, G, Amin, N, Arking, DE, Ayers, KL, Barbieri, CM, Batini, C, Bis, JC, Blake, T, Bochud, M, Boehnke, M, Boerwinkle, E, Boomsma, DI, Bottinger, EP, Braund, PS, Brumat, M, Campbell, A, Campbell, H, Chakravarti, A, Chambers, JC, Chauhan, G, Ciullo, M, Cocca, M, Collins, F, Cordell, HJ, Davies, G, De Borst, MH, De Geus, EJ, Deary, IJ, Deelen, J, Del Greco, FM, Demirkale, CY, Dorr, M, Ehret, GB, Elosua, R, Enroth, S, Erzurumluoglu, AM, Ferreira, T, Franberg, M, Franco, OH, Gandin, I, Gasparini, P, Giedraitis, V, Gieger, C, Girotto, G, Goel, A, Gow, AJ, Gudnason, V, Guo, X, Gyllensten, U, Hamsten, A, Harris, TB, Harris, SE, Hartman, CA, Havulinna, AS, Hicks, AA, Hofer, E, Hofman, A, Hottenga, J-J, Huffman, JE, Hwang, S-J, Ingelsson, E, James, A, Jansen, R, Jarvelin, M-R, Joehanes, R, Johansson, A, Johnson, AD, Joshi, PK, Jousilahti, P, Jukema, JW, Jula, A, Kahonen, M, Kathiresan, S, Keavney, BD, Khaw, K-T, Knekt, P, Knight, J, Kolcic, I, Kooner, JS, Koskinen, S, Kristiansson, K, Kutalik, Z, Laan, M, Larson, M, Launer, LJ, Lehne, B, Lehtimaki, T, Liewald, DCM, Lin, L, Lind, L, Lindgren, CM, Liu, Y, Loos, RJF, Lopez, LM, Lu, Y, Lyytikainen, L-P, Mahajan, A, Mamasoula, C, Marrugat, J, Marten, J, Milaneschi, Y, Morgan, A, Morris, AP, Morrison, AC, Munson, PJ, Nalls, MA, Nandakumar, P, Nelson, CP, Niiranen, T, Nolte, IM, Nutile, T, Oldehinkel, AJ, Oostra, BA, O'Reilly, PF, Org, E, Padmanabhan, S, Palmas, W, Palotie, A, Pattie, A, Penninx, BWJH, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Quang, TN, Raitakari, OT, Ren, M, Rettig, R, Rice, K, Ridker, PM, Ried, JS, Riese, H, Ripatti, S, Robino, A, Rose, LM, Rotter, JI, Rudan, I, Ruggiero, D, Saba, Y, Sala, CF, Salomaa, V, Samani, NJ, Sarin, A-P, Schmidt, R, Schmidt, H, Shrine, N, Siscovick, D, Smith, AV, Snieder, H, Sober, S, Sorice, R, Starr, JM, Stott, DJ, Strachan, DP, Strawbridge, RJ, Sundstrom, J, Swertz, MA, Taylor, KD, Teumer, A, Tobin, MD, Tomaszewski, M, Toniolo, D, Traglia, M, Trompet, S, Tuomilehto, J, Tzourio, C, Uitterlinden, AG, Vaez, A, Van der Most, PJ, Van Duijn, CM, Vergnaud, A-C, Verwoert, GC, Vitart, V, Volker, U, Vollenweider, P, Vuckovic, D, Watkins, H, Wild, SH, Willemsen, G, Wilson, JF, Wright, AF, Yao, J, Zemunik, T, Zhang, W, Attia, JR, Butterworth, AS, Chasman, DI, Conen, D, Cucca, F, Danesh, J, Hayward, C, Howson, JMM, Laakso, M, Lakatta, EG, Langenberg, C, Melander, O, Mook-Kanamori, DO, Palmer, CNA, Risch, L, Scott, RA, Scott, RJ, Sever, P, Spector, TD, Van der Harst, P, Wareham, NJ, Zeggini, E, Levy, D, Munroe, PB, Newton-Cheh, C, Brown, MJ, Metspalu, A, Hung, AM, O'Donnell, CJ, Edwards, TL, Psaty, BM, Tzoulaki, I, Barnes, MR, Wain, LV, Elliott, P, and Caulfield, MJ

Subjects
Genetics & Heredity, Science & Technology, Million Veteran Program, 06 Biological Sciences, Life Sciences & Biomedicine, 11 Medical and Health Sciences, Developmental Biology
Abstract

Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.

Published
2018

22. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author

EVANGELOU, E., WARREN, H. R., MOSEN-ANSORENA, D., MIFSUD, B., PAZOKI, R., Gao, H., NTRITSOS, G., DIMOU, N., CABRERA, C. P., Karaman, I., NG, F. L., Evangelou, M., WITKOWSKA, K., TZANIS, E., HELLWEGE, J. N., Giri, A., VELEZ EDWARDS, D. R., Sun, Y. V., Cho, K., GAZIANO, J. M., WILSON, P. W. F., TSAO, P. S., Kovesdy, C. P., ESKO, T., MAGI, R., Milani, L., Almgren, P., Boutin, T., Debette, Stéphanie, Ding, J., GIULIANINI, F., HOLLIDAY, E. G., JACKSON, A. U., LI-GAO, R., LIN, W. Y., Luan, J., Mangino, M., OLDMEADOW, C., PRINS, B. P., Qian, Y., Sargurupremraj, Muralidharan, Shah, N., SURENDRAN, P., THERIAULT, S., VERWEIJ, N., WILLEMS, S. M., Zhao, J. H., Amouyel, P., Connell, J., DE MUTSERT, R., DONEY, A. S. F., Farrall, M., MENNI, C., NOORDAM, R., Pare, G., POULTER, N. R., SHIELDS, D. C., STANTON, A., THOM, S., ABECASIS, G., Amin, N., ARKING, D. E., Ayers, K. L., BARBIERI, C. M., Batini, C., BIS, J. C., Blake, T., Bochud, M., Boehnke, M., BOERWINKLE, E., Boomsma, D. I., BOTTINGER, E. P., BRAUND, P. S., BRUMAT, M., Campbell, A., Campbell, H., Chakravarti, A., CHAMBERS, J. C., Chauhan, Ganesh, Ciullo, M., COCCA, M., Collins, F., CORDELL, H. J., Davies, G., DE BORST, M. H., DE GEUS, E. J., DEARY, I. J., DEELEN, J., DEL GRECO, M. F., DEMIRKALE, C. Y., DORR, M., EHRET, G. B., ELOSUA, R., ENROTH, S., ERZURUMLUOGLU, A. M., Ferreira, T., Franberg, M., FRANCO, O. H., GANDIN, I., Gasparini, P., GIEDRAITIS, V., Gieger, C., GIROTTO, G., Goel, A., GOW, A. J., GUDNASON, V., Guo, X., GYLLENSTEN, U., HAMSTEN, A., HARRIS, T. B., Harris, S. E., HARTMAN, C. A., HAVULINNA, A. S., HICKS, A. A., Hofer, E., Hofman, A., HOTTENGA, J. J., HUFFMAN, J. E., Hwang, S. J., INGELSSON, E., James, A., Jansen, R., JARVELIN, M. R., JOEHANES, R., Johansson, A., JOHNSON, A. D., Joshi, P. K., JOUSILAHTI, P., JUKEMA, J. W., JULA, A., KAHONEN, M., KATHIRESAN, S., KEAVNEY, B. D., Khaw, K. T., KNEKT, P., Knight, J., KOLCIC, I., KOONER, J. S., KOSKINEN, S., KRISTIANSSON, K., KUTALIK, Z., Laan, M., Larson, M., LAUNER, L. J., LEHNE, B., LEHTIMAKI, T., LIEWALD, D. C. M., Lin, L., LIND, L., LINDGREN, C. M., Liu, Y., LOOS, R. J. F., LOPEZ, L. M., Lu, Y., LYYTIKAINEN, L. P., Mahajan, A., MAMASOULA, C., MARRUGAT, J., MARTEN, J., MILANESCHI, Y., Morgan, A., MORRIS, A. D., MORRISON, A. C., MUNSON, P. J., Nalls, M. A., NANDAKUMAR, P., NELSON, C. P., NIIRANEN, T., Nolte, I. M., Nutile, T., Oldehinkel, A. J., Oostra, B. A., O'REILLY, P. F., ORG, E., PADMANABHAN, S., PALMAS, W., Palotie, A., PATTIE, A., PENNINX, Bwjh, Perola, M., Peters, A., POLASEK, O., PRAMSTALLER, P. P., Nguyen, Q. T., RAITAKARI, O. T., REN, M., Rettig, R., Rice, K., RIDKER, P. M., RIED, J. S., RIESE, H., RIPATTI, S., ROBINO, A., ROSE, L. M., ROTTER, J. I., RUDAN, I., Ruggiero, D., SABA, Y., SALA, C. F., SALOMAA, V., SAMANI, N. J., SARIN, A. P., Schmidt, R., Schmidt, H., SHRINE, N., SISCOVICK, D., SMITH, A. V., SNIEDER, H., SOBER, S., Sorice, R., STARR, J. M., STOTT, D. J., Strachan, D. P., STRAWBRIDGE, R. J., SUNDSTROM, J., SWERTZ, M. A., TAYLOR, K. D., TEUMER, A., TOBIN, M. D., TOMASZEWSKI, M., TONIOLO, D., TRAGLIA, M., TROMPET, S., TUOMILEHTO, J., Tzourio, Christophe, UITTERLINDEN, A. G., VAEZ, A., VAN DER MOST, P. J., VAN DUIJN, C. M., VERGNAUD, A. C., VERWOERT, G. C., Vitart, V., VOLKER, U., Vollenweider, P., VUCKOVIC, D., WATKINS, H., WILD, S. H., Willemsen, G., WILSON, J. F., WRIGHT, A. F., Yao, J., ZEMUNIK, T., Zhang, W., ATTIA, J. R., BUTTERWORTH, A. S., Chasman, D. I., CONEN, D., Cucca, F., DANESH, J., Hayward, C., HOWSON, J. M. M., Laakso, M., LAKATTA, E. G., Langenberg, C., MELANDER, O., MOOK-KANAMORI, D. O., PALMER, C. N. A., Risch, L., SCOTT, R. A., SEVER, P., SPECTOR, T. D., Van Der Harst, P., Wareham, N. J., Zeggini, E., Levy, D., MUNROE, P. B., NEWTON-CHEH, C., Brown, M. J., Metspalu, A., HUNG, A. M., O'DONNELL, C. J., EDWARDS, T. L., PSATY, B. M., TZOULAKI, I., BARNES, M. R., WAIN, L. V., Elliott, P., CAULFIELD, M. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY
Abstract

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Published
2018

23. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author

Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), Caulfield, M. (Mark), Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), and Caulfield, M. (Mark)

Abstract

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Published
2018
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24. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author

Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), and Soranzo, N. (Nicole)

Abstract

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

Published
2018
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25. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the c

Published
2018
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26. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

27. Genetic predisposition to high blood pressure and lifestyle factors. Associations with midlife blood pressure levels and cardiovascular events

Author

Pazoki, R, Dehghan, A, Evangelou, E, Warren, H, Gao, H, Caulfield, M, Elliott, P, Tzoulaki, I, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), and British Heart Foundation

Subjects
Male, Cardiac & Cardiovascular Systems, Blood Pressure, Body Mass Index, 1117 Public Health and Health Services, healthy lifestyle, Risk Factors, Humans, genetics, COHORT, Genetic Predisposition to Disease, Life Style, 1102 Cardiorespiratory Medicine and Haematology, risk, EXCRETION, Science & Technology, HYPERTENSION, 1103 Clinical Sciences, Middle Aged, cardiovascular diseases, INTERSALT, INDIVIDUALS, PATTERN, PHYSICAL-ACTIVITY, Peripheral Vascular Disease, Cardiovascular System & Hematology, Genetic Loci, REGRESSION DILUTION BIAS, Cardiovascular System & Cardiology, RISK-FACTORS, Female, Diet, Healthy, Life Sciences & Biomedicine, Follow-Up Studies
Abstract

Background: High blood pressure (BP) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to elevated BP levels. We aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse BP genetic profile and its effect on CVD risk. Methods: We constructed a genetic risk score for high BP by using 314 published BP loci in 277 005 individuals without previous CVD from the UK Biobank study, a prospective cohort of individuals aged 40 to 69 years, with a median of 6.11 years of follow-up. We scored participants according to their lifestyle factors including body mass index, healthy diet, sedentary lifestyle, alcohol consumption, smoking, and urinary sodium excretion levels measured at recruitment. We examined the association between tertiles of genetic risk and tertiles of lifestyle score with BP levels and incident CVD by using linear regression and Cox regression models, respectively. Results: Healthy lifestyle score was strongly associated with BP (P

Published
2017

28. No association between gluten sensitivity and amyotrophic lateral sclerosis

Author

Visser, A.E., Pazoki, R., Pulit, S.L., Rheenen, W. van, Raaphorst, J., Kooi, A.J. van der, Ricano-Ponce, I., Wijmenga, C., Otten, H.G., Veldink, J.H., Berg, L.H. van den, Visser, A.E., Pazoki, R., Pulit, S.L., Rheenen, W. van, Raaphorst, J., Kooi, A.J. van der, Ricano-Ponce, I., Wijmenga, C., Otten, H.G., Veldink, J.H., and Berg, L.H. van den

Abstract

Contains fulltext : 170399.pdf (publisher's version ) (Open Access), To examine evidence for a role of gluten sensitivity (GS) or celiac disease (CD) in ALS etiology, we included participants from a population-based case-control study in The Netherlands between January 2006 and December 2015. We compared levels and seroprevalence of IgA antibodies to tissue transglutaminase 6 (TG6) in 359 ALS patients and 359 controls, and to transglutaminase 2 (TG2) and endomysium (EMA) in 199 ALS patients and 199 controls. Questionnaire data on 1829 ALS patients and 3920 controls were examined for CD or gluten-free diets (GFD). Genetic correlation and HLA allele frequencies were analyzed using two genome-wide association studies: one on ALS (12,577 cases, 23,475 controls), and one on CD (4533 cases, 10,750 controls). We found one patient with TG6, TG2 and EMA antibodies who had typical ALS and no symptoms of GS. TG6 antibody concentrations and positivity, CD prevalence and adherence to a GFD were similar in patients and controls (p > 0.66) and in these patients disease progression was compatible with typical ALS. CD and ALS were not found to be genetically correlated (p > 0.37). CD-associated HLA allele frequencies were similar in patients and controls (p > 0.28). In conclusion, we found no serological evidence for involvement of gluten-related antibodies in ALS etiology nor did we observe an association between CD and ALS in medical history or genetic data, indicating that there is no evidence in our data for an association between the two diseases. Hence, a role for a GFD in the ALS treatment seems unlikely.

Published
2017

29. The effects of (ethanolic, methanolic, and aqueous) extracts of Cinnamomum zeylanicum and Thymus vulgaris with clotrimazol ointment in preventing the growth of Candidad albicans fungus

Author

Saffarieh, E, Pazoki, R, Aghaamoo, S, and Jahan, E

Subjects
Extract, distilled extract, cinnamon, thyme, clotrimazole, candida albicans
Abstract

Background and Objectives: Considering the increasing demand for applying medicinal plants in the medical treatment, this study aimed to investigatethe effect of cinnamon and thyme extracts alone and in comparison with clotrimazole ointment on the Candida albicans yeast in laboratory condition.Materials and Methods: In this study the cinnamon bark available in market was used for providing cinnamon products. The thymus vulgaris was prepared from the medicinal plants farm of Semnan Agricultural Jahad Training Centre.Ethanolic, methanolic and aqueous extracts of cinnamon and thyme powders prepared by maceration method.Then paper discs which coated with herbal products placed in candida albicans medium and their zone diameters of growth inhibition compared with that of clotrimazole ointment.Findings: The results of observations showed that the following items have the highestinhibition zone respectively: 1).The cinnamon methanolic extract 19.5 mm 2) the cinnamon extract3) Thyme extract 4) Cinnamon ethanolic extract 5) Thyme ethanolic extract.Conclusion: The results clearly showed thatboth cinnamon and thyme extracts have a significant effect in limiting fungal growth.Keywords: Extract; distilled extract; cinnamon; thyme; clotrimazole; candida albicans

Published
2016

30. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Schmidt, A.F., Swerdlow, D.I., Holmes, M.V., Patel, R.S., Fairhurst-Hunter, Z., Lyall, D.M., Hartwig, F.P., Horta, B.L., Hypponen, E., Power, C., Moldovan, M., Iperen, E. van, Hovingh, G.K., Demuth, I., Norman, K., Steinhagen-Thiessen, E., Demuth, J., Bertram, L., Liu, T., Coassin, S., Willeit, J., Kiechl, S., Willeit, K., Mason, D., Wright, J., Morris, R., Wanamethee, G., Whincup, P., Ben-Shlomo, Y., McLachlan, S., Price, J.F., Kivimaki, M., Welch, C., Sanchez-Galvez, A., Marques-Vidal, P., Nicolaides, A., Panayiotou, A.G., Onland-Moret, N.C., Schouw, Y.T. van der, Matullo, G., Fiorito, G., Guarrera, S., Sacerdote, C., Wareham, N.J., Langenberg, C., Scott, R., Luan, J.A., Bobak, M., Malyutina, S.A., Pajak, A., Kubinova, R., Tamosiunas, A., Pikhart, H., Husemoen, L.L.N., Grarup, N., Pedersen, O., Hansen, T., Linneberg, A., Simonsen, K.S., Cooper, J., Humphries, S.E., Brilliant, M., Kitchner, T., Hakonarson, H., Carrell, D.S., McCarty, C.A., Kirchner, H.L., Larson, E.B., Crosslin, D.R., Andrade, M. de, Roden, D.M., Denny, J.C., Carty, C., Hancock, S., Attia, J., Holliday, E., Donnell, M.O., Yusuf, S., Chong, M., Pare, G., Harst, P. van der, Said, M.A., Eppinga, R.N., Verweij, N., Snieder, H., Christen, T., Mook-Kanamori, D.O., Gustafsson, S., Lind, L., Ingelsson, E., Pazoki, R., Franco, O., Hofman, A., Uitterlinden, A., Dehghan, A., Teumer, A., Baumeister, S., Dorr, M., Lerch, M.M., Volker, U., Volzke, H., Ward, J., Pell, J.P., Smith, D.J., Meade, T., Maitland-van der Zee, A.H., Baranova, E.V., Young, R., Ford, I., Campbell, A., Padmanabhan, S., Bots, M.L., Grobbee, D.E., Froguel, P., Thuillier, D., Balkau, B., Bonnefond, A., Cariou, B., Smart, M., Bao, Y., Kumari, M., Mahajan, A., Ridker, P.M., Chasman, D.I., Reiner, A.P., Lange, L.A., Ritchie, M.D., Asselbergs, F.W., Casas, J.P., Keating, B.J., Preiss, D., Hingorani, A.D., Sattar, N., LifeLines Cohort Study Grp, UCLEB Consortium, Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dept. of Gastroenterology, Hepatology and Endocrinology, Neuroepidemiology of Ageing Research Unit, Imperial College London, Institut des Sciences Moléculaires (ISM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), Division of Community Health Sciences, St George's University of London, Department of Social Medicine, University of Bristol [Bristol], Finnish Institute of Occupational Health of Helsinki, Department of Epidemiology and Public Health, Institute of Social and Preventive Medicine, Lausanne university hospital, Computer Science Department, University of Cyprus, Cyprus Institute of Neurology and Genetics, University Medical Center [Utrecht], Department of Genetics, Biology and Biochemistry, University of Turin, Institute for Scientific Interchange Foundation, Center for Cancer Prevention, CPO-Piemonte, Unità di epidemiologia dei tumori, Università degli studi di Torino (UNITO)-HuGeF Foundation, Medical Research Council Epidemiology Unit, University of Cambridge [UK] (CAM), Serono Genetics Institute S.A.[Evry], Serono Genetics Institute, Institute of Internal and Preventive Medicine Sibe rian Branch, Russian Academy of Medical Sciences, Institute of Internal Medicine, Novosibirsk State Medical University, Centre for Environmental Health, National Institute of Public Health [Prague], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, Rigshospitalet [Copenhagen], Copenhagen University Hospital, BHF Laboratories, Rayne building, Department of Medicine, 5 University Street, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Population Health Research Institute, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen [Groningen], Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Limnology, Ecology, Uppsala Universitet [Uppsala], Metacohorts Consortium, Erasmus University Medical Center [Rotterdam] (Erasmus MC), King‘s College London, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Institute for Community Medicine, Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], European Associated Laboratory [Sheffield, UK] (Sarcoma Research Unit), Robertson Centre for Biostatistics, University of Glasgow, Faculty of Medicine, University of Glasgow, Julius Center for Health Sciences and Primary Care, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), INSERM UMRS 1178, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Department of Pathological Biochemistry, Royal Infirmary, Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], and Apollo - University of Cambridge Repository

Subjects
Blood Glucose, Cohort Studies, Diabetes Mellitus, Type 2, Case-Control Studies, [SDV]Life Sciences [q-bio], Genetic Variation, Humans, Genetic Predisposition to Disease, Cholesterol, LDL, Mendelian Randomization Analysis, Proprotein Convertase 9, Randomized Controlled Trials as Topic
Abstract

BACKGROUND:Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS:In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS:Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30).INTERPRETATION:PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.FUNDING:British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.

Published
2016

31. Subcloning and Expression of Recombinant Echinococcus granulosus Antigen B, in Pqe-30 Expression Vector

Author

Taghipour, N., Bandepour, M., Pazoki, R., Ali Haghighi, Nazari Pouya, M. R., and Kazemi, B.

Subjects
Cystic echinococcosis, Recombinant antigen B, lcsh:RC109-216, HI gene, lcsh:Infectious and parasitic diseases
Abstract

"nBackground: Echinococcosis or hydatid disease is a zoonotic infection caused by larval (metacestode) stages of cestodes belonging to the genus Echinococcus, family Taeniidae. We aimed to subclone antigen B gene in pQE-30 plasmid, its expression, and purification."nMethods: We subcloned HI gene into pQE-30 expression vector. The recombinant vector was transformed into E. coli, M15 and mass cultured. The subcloned gene was expressed by IPTG. Subcloning of gene was confirmed by both PCR and enzyme digestion."nResults: Production of recombinant protein was confirmed by SDS-PAGE. Western blot analysis was carried out by both His-Tag monoclonal Ab and human serum to estimate the expressed protein in E. coli cells. Recombinant protein was purified and its specificity was proved by Western blotting."nConclusion: Production of this recombinant protein can increase sensitivity and specificity in serological test (ELISA).

Published
2009

33. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

Author

Pankratz, V.S. (Shane), Schick, U.M. (Ursula), Zhou, Y. (Yi), Zhou, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Allende, M.L. (Maria Laura), Auer, P. (Paul), Bork-Jensen, J. (Jette), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Clavo, V. (Vinna), Eicher, J.D. (John D.), Grarup, N. (Niels), Hagedorn, E.J. (Elliott J.), Hu, B. (Bella), Hunker, K. (Kristina), Johnson, A.D. (Andrew), Leusink, M. (Maarten), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Marioni, R.E. (Riccardo), Nalls, M.A. (Michael), Pazoki, R. (Raha), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Yang, M.-L. (Min-Lee), Zhang, X. (Xiaoling), Zhang, Y. (Yan), Asselbergs, F.W. (Folkert), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Cushman, M. (Mary Ann), Bakker, P.I.W. (Paul) de, Deary, I.J. (Ian), Dong, L. (Liguang), Feitosa, M.F. (Mary Furlan), Floyd, J. (James), Franceschini, N. (Nora), Franco, O.H. (Oscar), Garcia, M. (Melissa), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jia, J. (Jia), Kähönen, M. (Mika), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Nguyen, V.M. (Vy M.), Numans, M.E. (Mattijs), Pedersen, O. (Oluf), Psaty, B.M. (Bruce M.), Raitakari, O.T. (Olli T.), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Di Sant, A.M.R. (Amanda M. Rosa), Rotter, J.I. (Jerome I.), Starr, J.M. (John), Taylor, K.D. (Kent), Thuesen, B.H. (Betina Heinsbek), Tracy, R.P. (Russell), Uitterlinden, A.G. (André), Wang, J. (Jiansong), Wang, J. (Judy), Dehghan, A. (Abbas), Huo, Y. (Yong), Cupples, L.A. (Adrienne), Wilson, J.F. (James), Proia, R.L. (Richard L.), Zon, L.I. (Leonard), O'Donnell, C.J. (Christopher), Reiner, A.P. (Alex P.), Ganesh, S.K. (Santhi), Pankratz, V.S. (Shane), Schick, U.M. (Ursula), Zhou, Y. (Yi), Zhou, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Allende, M.L. (Maria Laura), Auer, P. (Paul), Bork-Jensen, J. (Jette), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Clavo, V. (Vinna), Eicher, J.D. (John D.), Grarup, N. (Niels), Hagedorn, E.J. (Elliott J.), Hu, B. (Bella), Hunker, K. (Kristina), Johnson, A.D. (Andrew), Leusink, M. (Maarten), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Marioni, R.E. (Riccardo), Nalls, M.A. (Michael), Pazoki, R. (Raha), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Yang, M.-L. (Min-Lee), Zhang, X. (Xiaoling), Zhang, Y. (Yan), Asselbergs, F.W. (Folkert), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Cushman, M. (Mary Ann), Bakker, P.I.W. (Paul) de, Deary, I.J. (Ian), Dong, L. (Liguang), Feitosa, M.F. (Mary Furlan), Floyd, J. (James), Franceschini, N. (Nora), Franco, O.H. (Oscar), Garcia, M. (Melissa), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jia, J. (Jia), Kähönen, M. (Mika), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Nguyen, V.M. (Vy M.), Numans, M.E. (Mattijs), Pedersen, O. (Oluf), Psaty, B.M. (Bruce M.), Raitakari, O.T. (Olli T.), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Di Sant, A.M.R. (Amanda M. Rosa), Rotter, J.I. (Jerome I.), Starr, J.M. (John), Taylor, K.D. (Kent), Thuesen, B.H. (Betina Heinsbek), Tracy, R.P. (Russell), Uitterlinden, A.G. (André), Wang, J. (Jiansong), Wang, J. (Judy), Dehghan, A. (Abbas), Huo, Y. (Yong), Cupples, L.A. (Adrienne), Wilson, J.F. (James), Proia, R.L. (Richard L.), Zon, L.I. (Leonard), O'Donnell, C.J. (Christopher), Reiner, A.P. (Alex P.), and Ganesh, S.K. (Santhi)

Abstract

Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.

Published
2016
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34. PCSK9 genetic variants and risk of type 2 diabetes: A mendelian randomisation study

Author

Schmidt, A.F. (Amand F.), Swerdlow, D.I. (Daniel), Holmes, M.V. (Michael), Patel, R.S. (Riyaz), Fairhurst-Hunter, Z. (Zammy), Lyall, D.M. (Donald M.), Hartwig, F.P. (Fernando Pires), Horta, B.L. (Bernardo Lessa), Hypponen, E. (Elina), Power, C. (Christopher), Moldovan, M. (Max), Iperen, E.P.A. (Erik) van, Hovingh, G.K. (Kees), Demuth, I. (Ilja), Norman, K. (Kristina), Steinhagen-Thiessen, E. (Elisabeth), Demuth, J. (Juri), Bertram, L. (Lars), Liu, T. (Tian), Coassin, S. (Stefan), Willeit, J. (Johann), Kiechl, S. (Stefan), Willeit, K. (Karin), Mason, D. (Dan), Wright, J. (Juliet), Morris, R.W. (Richard), Wanamethee, G. (Goya), Whincup, P.H. (Peter), Ben-Shlomo, Y., McLachlan, S. (Stela), Price, J.F. (Jackie F.), Kivimaki, M. (Mika), Welch, C. (Catherine), Sanchez-Galvez, A. (Adelaida), Marques-Vidal, P. (Pedro), Nicolaides, A.N. (Andrew), Panayiotou, A.G. (Andrie), Onland-Moret, N.C. (N Charlotte), Schouw, Y.T. (Yvonne) van der, Matullo, G., Fiorito, G. (Giovanni), Guarrera, S. (Simonetta), Sacerdote, C. (Carlotta), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Scott, R. (Robert), Luan, J. (Jian'an), Bobak, M. (Martin), Malyutina, S., Pajak, A. (Andrzej), Kubinova, R., Tamosiunas, A. (Abdonas), Pikhart, H. (Hynek), Husemoen, L.L.N. (Lise Lotte), Grarup, N. (Niels), Pedersen, O. (Oluf), Hansen, T. (T.), Linneberg, A. (Allan), Simonsen, K.S. (Kenneth Starup), Cooper, J. (Jim), Humphries, S.E. (Steve), Brilliant, M.H. (Murray H.), Kitchner, T.E. (Terrie E.), Hakonarson, H. (Hakon), Carrell, D.S. (David), McCarty, C.A. (Catherine A.), Kirchner, H.L. (H Lester), Larson, E.B. (Eric B.), Crosslin, D.R. (David), de Andrade, M. (Mariza), Roden, D.M. (Dan M.), Denny, J.C. (Joshua C.), Carty, C. (Cara), Hancock, S. (Stephen), Attia, J. (John), Holliday, E.G. (Elizabeth), Donnell, M.O.'. (Martin O'), Yusuf, S. (Salim), Chong, M. (Michael), Pare, G. (Guillame), Harst, P. (Pim) van der, Said, M.A. (M Abdullah), Eppinga, R.N. (Ruben N.), Verweij, N. (Niek), Snieder, H. (Harold), Christen, T. (Tim), Mook-Kanamori, D.O. (Dennis), Gustafsson, S. (Stefan), Kao, W.H.L. (Wen), Ingelsson, E. (Erik), Pazoki, R. (Raha), Franco, O.H. (Oscar), Hofman, A. (Albert), Uitterlinden, A.G. (André), Dehghan, A. (Abbas), Teumer, A. (Alexander), Baumeister, S.E. (Sebastian), Dörr, M. (Marcus), Lerch, M.M. (Markus M.), Völker, U. (Uwe), Völzke, H. (Henry), Ward, J. (Joey), Pell, J.P. (Jill P.), Smith, D.J. (Daniel J.), Meade, T. (Tom), Maitland-van der Zee, A-H. (Anke-Hilse), Baranova, E.V. (Ekaterina V.), Young, R. (Robin), Ford, I. (Ian), Campbell, A. (Archie), Padmanabhan, S. (Sandosh), Bots, M.L. (Michiel), Grobbee, D.E. (Diederick E.), Froguel, P. (Philippe), Thuillier, D. (Dorothee), Balkau, B. (Beverley), Bonnefond, A. (Amélie), Cariou, B. (Bertrand), Smart, M. (Melissa), Bao, Y. (Yanchun), Kumari, M. (Meena), Mahajan, A. (Anubha), Ridker, P.M. (Paul), Chasman, D.I. (Daniel I.), Reiner, A. (Alexander), Lange, L.A. (Leslie), Ritchie, M.D. (Marylyn D.), Asselbergs, F.W. (Folkert), Casas, J.P. (Juan), Keating, J. (John), Preiss, D. (David), Hingorani, A. (Aroon), Sattar, N. (Naveed), Schmidt, A.F. (Amand F.), Swerdlow, D.I. (Daniel), Holmes, M.V. (Michael), Patel, R.S. (Riyaz), Fairhurst-Hunter, Z. (Zammy), Lyall, D.M. (Donald M.), Hartwig, F.P. (Fernando Pires), Horta, B.L. (Bernardo Lessa), Hypponen, E. (Elina), Power, C. (Christopher), Moldovan, M. (Max), Iperen, E.P.A. (Erik) van, Hovingh, G.K. (Kees), Demuth, I. (Ilja), Norman, K. (Kristina), Steinhagen-Thiessen, E. (Elisabeth), Demuth, J. (Juri), Bertram, L. (Lars), Liu, T. (Tian), Coassin, S. (Stefan), Willeit, J. (Johann), Kiechl, S. (Stefan), Willeit, K. (Karin), Mason, D. (Dan), Wright, J. (Juliet), Morris, R.W. (Richard), Wanamethee, G. (Goya), Whincup, P.H. (Peter), Ben-Shlomo, Y., McLachlan, S. (Stela), Price, J.F. (Jackie F.), Kivimaki, M. (Mika), Welch, C. (Catherine), Sanchez-Galvez, A. (Adelaida), Marques-Vidal, P. (Pedro), Nicolaides, A.N. (Andrew), Panayiotou, A.G. (Andrie), Onland-Moret, N.C. (N Charlotte), Schouw, Y.T. (Yvonne) van der, Matullo, G., Fiorito, G. (Giovanni), Guarrera, S. (Simonetta), Sacerdote, C. (Carlotta), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Scott, R. (Robert), Luan, J. (Jian'an), Bobak, M. (Martin), Malyutina, S., Pajak, A. (Andrzej), Kubinova, R., Tamosiunas, A. (Abdonas), Pikhart, H. (Hynek), Husemoen, L.L.N. (Lise Lotte), Grarup, N. (Niels), Pedersen, O. (Oluf), Hansen, T. (T.), Linneberg, A. (Allan), Simonsen, K.S. (Kenneth Starup), Cooper, J. (Jim), Humphries, S.E. (Steve), Brilliant, M.H. (Murray H.), Kitchner, T.E. (Terrie E.), Hakonarson, H. (Hakon), Carrell, D.S. (David), McCarty, C.A. (Catherine A.), Kirchner, H.L. (H Lester), Larson, E.B. (Eric B.), Crosslin, D.R. (David), de Andrade, M. (Mariza), Roden, D.M. (Dan M.), Denny, J.C. (Joshua C.), Carty, C. (Cara), Hancock, S. (Stephen), Attia, J. (John), Holliday, E.G. (Elizabeth), Donnell, M.O.'. (Martin O'), Yusuf, S. (Salim), Chong, M. (Michael), Pare, G. (Guillame), Harst, P. (Pim) van der, Said, M.A. (M Abdullah), Eppinga, R.N. (Ruben N.), Verweij, N. (Niek), Snieder, H. (Harold), Christen, T. (Tim), Mook-Kanamori, D.O. (Dennis), Gustafsson, S. (Stefan), Kao, W.H.L. (Wen), Ingelsson, E. (Erik), Pazoki, R. (Raha), Franco, O.H. (Oscar), Hofman, A. (Albert), Uitterlinden, A.G. (André), Dehghan, A. (Abbas), Teumer, A. (Alexander), Baumeister, S.E. (Sebastian), Dörr, M. (Marcus), Lerch, M.M. (Markus M.), Völker, U. (Uwe), Völzke, H. (Henry), Ward, J. (Joey), Pell, J.P. (Jill P.), Smith, D.J. (Daniel J.), Meade, T. (Tom), Maitland-van der Zee, A-H. (Anke-Hilse), Baranova, E.V. (Ekaterina V.), Young, R. (Robin), Ford, I. (Ian), Campbell, A. (Archie), Padmanabhan, S. (Sandosh), Bots, M.L. (Michiel), Grobbee, D.E. (Diederick E.), Froguel, P. (Philippe), Thuillier, D. (Dorothee), Balkau, B. (Beverley), Bonnefond, A. (Amélie), Cariou, B. (Bertrand), Smart, M. (Melissa), Bao, Y. (Yanchun), Kumari, M. (Meena), Mahajan, A. (Anubha), Ridker, P.M. (Paul), Chasman, D.I. (Daniel I.), Reiner, A. (Alexander), Lange, L.A. (Leslie), Ritchie, M.D. (Marylyn D.), Asselbergs, F.W. (Folkert), Casas, J.P. (Juan), Keating, J. (John), Preiss, D. (David), Hingorani, A. (Aroon), and Sattar, N. (Naveed)

Abstract

Background: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering . PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. Methods: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). Interpretation: . PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibi

Published
2016
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35. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

Author

Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), Lettre, G. (Guillaume), Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), and Lettre, G. (Guillaume)

Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10−10 for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10−8 for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribut

Published
2016
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36. Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis

Author

Polfus, L.M. (Linda M.), Khajuria, R.K. (Rajiv K.), Schick, U.M. (Ursula), Pankratz, V.S. (Shane), Pazoki, R. (Raha), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Auer, P. (Paul), Floyd, J. (James), Huang, J. (Jian), Lange, L.A. (Leslie), Rooij, F.J.A. (Frank) van, Gibbs, R.A. (Richard), Metcalf, G.A. (Ginger A.), Muzny, D. (Donna), Veeraraghavan, N. (Narayanan), Walter, K. (Klaudia), Chen, L. (Lu), Yanek, L.R. (Lisa), Becker, L.C. (Lewis), Peloso, G.M. (Gina), Wakabayashi, A. (Aoi), Kals, M. (Mart), Metspalu, A. (Andres), Esko, T. (Tõnu), Fox, K. (Keolu), Wallace, R. (Robert), Franceshini, N. (Nora), Aleksic, N. (Nena), Rice, K.M. (Kenneth), Bartz, T.M. (Traci M.), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O.T. (Olli T.), Li-Gao, R. (Ruifang), Mook-Kanamori, D.O. (Dennis), Lettre, G. (Guillaume), Duijn, C.M. (Cornelia) van, Franco, O.H. (Oscar), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wilson, J.F. (James), Psaty, B.M. (Bruce), Soranzo, N. (Nicole), Dehghan, A. (Abbas), Boerwinkle, E.A. (Eric), Zhang, X. (Xiaoling), Johnson, A.D. (Andrew), O'Donnell, C.J. (Christopher), Johnsen, J.M. (Jill M.), Reiner, A. (Alexander), Ganesh, S.K. (Santhi), Sankaran, V.G. (Vijay G.), Polfus, L.M. (Linda M.), Khajuria, R.K. (Rajiv K.), Schick, U.M. (Ursula), Pankratz, V.S. (Shane), Pazoki, R. (Raha), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Auer, P. (Paul), Floyd, J. (James), Huang, J. (Jian), Lange, L.A. (Leslie), Rooij, F.J.A. (Frank) van, Gibbs, R.A. (Richard), Metcalf, G.A. (Ginger A.), Muzny, D. (Donna), Veeraraghavan, N. (Narayanan), Walter, K. (Klaudia), Chen, L. (Lu), Yanek, L.R. (Lisa), Becker, L.C. (Lewis), Peloso, G.M. (Gina), Wakabayashi, A. (Aoi), Kals, M. (Mart), Metspalu, A. (Andres), Esko, T. (Tõnu), Fox, K. (Keolu), Wallace, R. (Robert), Franceshini, N. (Nora), Aleksic, N. (Nena), Rice, K.M. (Kenneth), Bartz, T.M. (Traci M.), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O.T. (Olli T.), Li-Gao, R. (Ruifang), Mook-Kanamori, D.O. (Dennis), Lettre, G. (Guillaume), Duijn, C.M. (Cornelia) van, Franco, O.H. (Oscar), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wilson, J.F. (James), Psaty, B.M. (Bruce), Soranzo, N. (Nicole), Dehghan, A. (Abbas), Boerwinkle, E.A. (Eric), Zhang, X. (Xiaoling), Johnson, A.D. (Andrew), O'Donnell, C.J. (Christopher), Johnsen, J.M. (Jill M.), Reiner, A. (Alexander), Ganesh, S.K. (Santhi), and Sankaran, V.G. (Vijay G.)

Abstract

Circulating blood cell counts and indices are important indicators of hematopoietic function and a number of clinical parameters, such as blood oxygen-carrying capacity, inflammation, and hemostasis. By performing whole-exome sequence association analyses of hematologic quantitative traits in 15,459 community-dwelling individuals, followed by in silico replication in up to 52,024 independent samples, we identified two previously undescribed coding variants associated with lower platelet count: a common missense variant in CPS1 (rs1047891, MAF = 0.33, discovery + replication p = 6.38 × 10−10) and a rare synonymous variant in GFI1B (rs150813342, MAF = 0.009, discovery + replication p = 1.79 × 10−27). By performing CRISPR/Cas9 genome editing in hematopoietic cell lines and follow-up targeted knockdown experiments in primary human hematopoietic stem and progenitor cells, we demonstrate an alternative splicing mechanism by which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that pref

Published
2016
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37. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author

Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), and Soranzo, N. (Nicole)

Abstract

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.

Published
2016
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38. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Author

Eicher, J.D. (John D.), Chami, N. (Nathalie), Kacprowski, T. (Tim), Nomura, A. (Akihiro), Chen, M.-H. (Ming-Huei), Yanek, L.R. (Lisa), Tajuddin, S.M. (Salman M.), Schick, U.M. (Ursula), Slater, A.J. (Andrew J.), Pankratz, V.S. (Shane), Polfus, L. (Linda), Schurmann, C. (Claudia), Giri, A. (Ayush), Brody, J.A. (Jennifer A.), Lange, L.A. (Leslie), Manichaikul, A. (Ani), Hill, W.D. (W. David), Pazoki, R. (Raha), Elliot, P. (Paul), Evangelou, E. (Evangelos), Tzoulaki, I., Gao, H. (He), Vergnaud, A.-C. (Anne-Claire), Mathias, J. (Jasmine), Becker, D.M. (Diane), Becker, L.C. (Lewis), Burt, A.D. (Alastair), Crosslin, D.R. (David), Lyytikäinen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Hernesniemi, J. (Jussi), Kähönen, M. (Mika), Raitoharju, E. (Emma), Mononen, K. (Kari), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Cushman, M. (Mary Ann), Zakai, N.A. (Neil), Nickerson, D.A. (Deborah), Raffield, L.M. (Laura M.), Quarells, R. (Rakale), Willer, C.J. (Cristen), Peloso, G.M. (Gina), Abecasis, G.R. (Gonçalo), Liu, D. (Dajiang), Deloukas, P. (Panagiotis), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Fornage, M. (Myriam), Richard, M. (Melissa), Tardif, J.-C. (Jean-Claude), Rioux, J.D. (John D.), Dube, M.-P. (Marie-Pierre), de Denus, S. (Simon), Lu, Y. (Yingchang), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Smith, A.V. (Albert Vernon), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Gudnason, V. (Vilmundur), Velez Edwards, D.R. (Digna R.), Torstenson, E.S. (Eric S.), Liu, Y. (YongMei), Tracy, R.P. (Russell), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Highland, H. (Heather), Boerwinkle, E.A. (Eric), Li, J. (Jin), Lange, E.M. (Ethan), Wilson, J.F. (James), Mihailov, E. (Evelin), Mägi, R. (Reedik), Hirschhorn, J.N. (Joel), Metspalu, A. (Andres), Esko, T. (Tõnu), Vacchi-Suzzi, C. (Caterina), Nalls, M.A. (Michael), Zonderman, A.B., Evans, M.K. (Michele), Engström, G., Orho-Melander, M. (Marju), Melander, O. (Olle), O'Donoghue, M.L. (Michelle L.), Waterworth, D. (Dawn), Wallentin, L.C. (Lars), White, H.D. (Harvey D.), Floyd, J. (James), Bartz, T.M. (Traci M.), Rice, K.M. (Kenneth), Psaty, B.M. (Bruce), Starr, J.M. (John), Liewald, D.C.M. (David), Hayward, C. (Caroline), Deary, I.J. (Ian), Greinacher, A. (Andreas), Völker, U. (Uwe), Thiele, T. (Thomas), Völzke, H. (Henry), Rooij, F.J.A. (Frank) van, Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Kathiresan, S. (Sekar), Faraday, N. (Nauder), Auer, P. (Paul), Reiner, A. (Alexander), Lettre, G. (Guillaume), Johnson, A.D. (Andrew), Eicher, J.D. (John D.), Chami, N. (Nathalie), Kacprowski, T. (Tim), Nomura, A. (Akihiro), Chen, M.-H. (Ming-Huei), Yanek, L.R. (Lisa), Tajuddin, S.M. (Salman M.), Schick, U.M. (Ursula), Slater, A.J. (Andrew J.), Pankratz, V.S. (Shane), Polfus, L. (Linda), Schurmann, C. (Claudia), Giri, A. (Ayush), Brody, J.A. (Jennifer A.), Lange, L.A. (Leslie), Manichaikul, A. (Ani), Hill, W.D. (W. David), Pazoki, R. (Raha), Elliot, P. (Paul), Evangelou, E. (Evangelos), Tzoulaki, I., Gao, H. (He), Vergnaud, A.-C. (Anne-Claire), Mathias, J. (Jasmine), Becker, D.M. (Diane), Becker, L.C. (Lewis), Burt, A.D. (Alastair), Crosslin, D.R. (David), Lyytikäinen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Hernesniemi, J. (Jussi), Kähönen, M. (Mika), Raitoharju, E. (Emma), Mononen, K. (Kari), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Cushman, M. (Mary Ann), Zakai, N.A. (Neil), Nickerson, D.A. (Deborah), Raffield, L.M. (Laura M.), Quarells, R. (Rakale), Willer, C.J. (Cristen), Peloso, G.M. (Gina), Abecasis, G.R. (Gonçalo), Liu, D. (Dajiang), Deloukas, P. (Panagiotis), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Fornage, M. (Myriam), Richard, M. (Melissa), Tardif, J.-C. (Jean-Claude), Rioux, J.D. (John D.), Dube, M.-P. (Marie-Pierre), de Denus, S. (Simon), Lu, Y. (Yingchang), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Smith, A.V. (Albert Vernon), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Gudnason, V. (Vilmundur), Velez Edwards, D.R. (Digna R.), Torstenson, E.S. (Eric S.), Liu, Y. (YongMei), Tracy, R.P. (Russell), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Highland, H. (Heather), Boerwinkle, E.A. (Eric), Li, J. (Jin), Lange, E.M. (Ethan), Wilson, J.F. (James), Mihailov, E. (Evelin), Mägi, R. (Reedik), Hirschhorn, J.N. (Joel), Metspalu, A. (Andres), Esko, T. (Tõnu), Vacchi-Suzzi, C. (Caterina), Nalls, M.A. (Michael), Zonderman, A.B., Evans, M.K. (Michele), Engström, G., Orho-Melander, M. (Marju), Melander, O. (Olle), O'Donoghue, M.L. (Michelle L.), Waterworth, D. (Dawn), Wallentin, L.C. (Lars), White, H.D. (Harvey D.), Floyd, J. (James), Bartz, T.M. (Traci M.), Rice, K.M. (Kenneth), Psaty, B.M. (Bruce), Starr, J.M. (John), Liewald, D.C.M. (David), Hayward, C. (Caroline), Deary, I.J. (Ian), Greinacher, A. (Andreas), Völker, U. (Uwe), Thiele, T. (Thomas), Völzke, H. (Henry), Rooij, F.J.A. (Frank) van, Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Kathiresan, S. (Sekar), Faraday, N. (Nauder), Auer, P. (Paul), Reiner, A. (Alexander), Lettre, G. (Guillaume), and Johnson, A.D. (Andrew)

Abstract

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets’ important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

Published
2016
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39. The global impact of non-communicable diseases on macro-economic productivity: a systematic review

Author

Chaker, L. (Layal), Falla, A. (Abby), Lee, S.J. (Sven) van der, Muka, T. (Taulant), Imo, D. (David), Jaspers, L. (Loes), Colpani, V. (Veronica), Mendis, S. (Shanthi), Chowdhury, R. (Rajiv), Bramer, W.M. (Wichor), Pazoki, R. (Raha), Franco, O.H. (Oscar), Chaker, L. (Layal), Falla, A. (Abby), Lee, S.J. (Sven) van der, Muka, T. (Taulant), Imo, D. (David), Jaspers, L. (Loes), Colpani, V. (Veronica), Mendis, S. (Shanthi), Chowdhury, R. (Rajiv), Bramer, W.M. (Wichor), Pazoki, R. (Raha), and Franco, O.H. (Oscar)

Abstract

Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case–control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured i

Published
2015
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40. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals

Author

Arking, D.E. (Dan), Junttila, M.J. (Juhani), Goyette, P. (Philippe), Huertas-Vazquez, A. (Adriana), Eijgelsheim, M. (Mark), Blom, M.T. (Marieke), Newton-Cheh, C. (Christopher), Reinier, K. (Kyndaron), Teodorescu, C. (Carmen), Uy-Evanado, A. (Audrey), Carter-Monroe, N. (Naima), Kaikkonen, K.S. (Kari), Kortelainen, M.-L., Boucher, G. (Gabrielle), Lagacé, C. (Caroline), Moes, A. (Anna), Zhao, X., Kolodgie, F. (Frank), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Uitterlinden, A.G. (André), Marsman, R.F. (Roos), Pazoki, R. (Raha), Bardai, A. (Abdennasser), Koster, R.W. (Rudolph), Dehghan, A. (Abbas), Hwang, S.J., Bhatnagar, P. (Pallav), Post, W. (Wendy), Hilton, G. (Gina), Prineas, R.J. (Ronald), Li, M. (Man), Köttgen, A. (Anna), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Coresh, J. (Josef), Kao, W.H.L. (Wen), Psaty, B.M. (Bruce), Tomaselli, G.F. (Gordon), Sotoodehnia, N. (Nona), Siscovick, D.S. (David), Burke, G.L. (Greg), Marbán, E. (Eduardo), Spooner, P.M. (Peter), Cupples, L.A. (Adrienne), Jui, J. (Jonathan), Gunson, K. (Karen), Kesaniemi, Y.A. (Antero), Wilde, A.A.M. (Arthur), Tardif, J.-C. (Jean-Claude), O'Donnell, C.J. (Christopher), Bezzina, C.R. (Connie), Virmani, R. (Renu), Stricker, B.H.Ch. (Bruno), Tan, H.L. (Hanno), Albert, C.M. (Christine), Chakravarti, A. (Aravinda), Rioux, J.D. (John), Huikuri, H.V. (Heikki), Chugh, S.S. (Sumeet), Arking, D.E. (Dan), Junttila, M.J. (Juhani), Goyette, P. (Philippe), Huertas-Vazquez, A. (Adriana), Eijgelsheim, M. (Mark), Blom, M.T. (Marieke), Newton-Cheh, C. (Christopher), Reinier, K. (Kyndaron), Teodorescu, C. (Carmen), Uy-Evanado, A. (Audrey), Carter-Monroe, N. (Naima), Kaikkonen, K.S. (Kari), Kortelainen, M.-L., Boucher, G. (Gabrielle), Lagacé, C. (Caroline), Moes, A. (Anna), Zhao, X., Kolodgie, F. (Frank), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Uitterlinden, A.G. (André), Marsman, R.F. (Roos), Pazoki, R. (Raha), Bardai, A. (Abdennasser), Koster, R.W. (Rudolph), Dehghan, A. (Abbas), Hwang, S.J., Bhatnagar, P. (Pallav), Post, W. (Wendy), Hilton, G. (Gina), Prineas, R.J. (Ronald), Li, M. (Man), Köttgen, A. (Anna), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Coresh, J. (Josef), Kao, W.H.L. (Wen), Psaty, B.M. (Bruce), Tomaselli, G.F. (Gordon), Sotoodehnia, N. (Nona), Siscovick, D.S. (David), Burke, G.L. (Greg), Marbán, E. (Eduardo), Spooner, P.M. (Peter), Cupples, L.A. (Adrienne), Jui, J. (Jonathan), Gunson, K. (Karen), Kesaniemi, Y.A. (Antero), Wilde, A.A.M. (Arthur), Tardif, J.-C. (Jean-Claude), O'Donnell, C.J. (Christopher), Bezzina, C.R. (Connie), Virmani, R. (Renu), Stricker, B.H.Ch. (Bruno), Tan, H.L. (Hanno), Albert, C.M. (Christine), Chakravarti, A. (Aravinda), Rioux, J.D. (John), Huikuri, H.V. (Heikki), and Chugh, S.S. (Sumeet)

Abstract

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10-10). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs

Published
2011
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49. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author

Iotchkova, V, Huang, J, Morris, JA, Jain, D, Barbieri, C, Walter, K, Min, JL, Chen, L, Astle, W, Cocca, M, Deelen, P, Elding, H, Farmaki, A-E, Franklin, CS, Franberg, M, Gaunt, TR, Hofman, A, Jiang, T, Kleber, ME, Lachance, G, Luan, J, Malerba, G, Matchan, A, Mead, D, Memari, Y, Ntalla, I, Panoutsopoulou, K, Pazoki, R, Perry, JRB, Rivadeneira, F, Sabater-Lleal, M, Sennblad, B, Shin, S-Y, Southam, L, Traglia, M, Van Dijk, F, Van Leeuwen, EM, Zaza, G, Zhang, W, UK10K Consortium, Amin, N, Butterworth, A, Chambers, JC, Dedoussis, G, Dehghan, A, Franco, OH, Franke, L, Frontini, M, Gambaro, G, Gasparini, P, Hamsten, A, Issacs, A, Kooner, JS, Kooperberg, C, Langenberg, C, Marz, W, Scott, RA, Swertz, MA, Toniolo, D, Uitterlinden, AG, Van Duijn, CM, Watkins, H, Zeggini, E, Maurano, MT, Timpson, NJ, Reiner, AP, Auer, PL, and Soranzo, N

Subjects
Male, Heart Diseases, Genetic Loci, Genome, Human, Quantitative Trait Loci, Genetic Variation, Humans, Female, Genetic Predisposition to Disease, Sequence Analysis, DNA, Hematologic Diseases, 3. Good health, Genome-Wide Association Study
Abstract

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.

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