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5. List of Contributors

Author

Arnett, D.K., primary, Aslibekyan, S., additional, Bai, G., additional, Barreiro, E., additional, Basta, J., additional, Bayliss, P.E., additional, Bennett, D.A., additional, Carvajal, C.A., additional, Claas, S.A., additional, De Jager, P.L., additional, Dubner, R., additional, Fardella, C.E., additional, Friso, S., additional, Hanai, J., additional, Kelsey, K.T., additional, Kikyo, N., additional, Kishi, S., additional, Klein, H.-U., additional, Kobayashi, H., additional, Langevin, S.M., additional, Liu, N., additional, Lowe, M., additional, Olivieri, O., additional, Pan, T., additional, Pizzolo, F., additional, Rauchman, M., additional, Ren, K., additional, Yang, J., additional, and Yu, L., additional

Published
2017
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6. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., Räikkönen, K., Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., and Räikkönen, K.

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

7. Cerebral small vessel disease genomics and its implications across the lifespan

Author

Sargurupremraj, M., Suzuki, H., Jian, X., Sarnowski, C., Evans, T.E., Bis, J.C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N.J., Hofer, E., Yanek, L.R., Hagenaars, S.P., Kumar, R.B., van den Akker, E.B., McWhirter, R.E., Trompet, S., Mishra, A., Saba, Y., Satizabal, C.L., Beaudet, G., Petit, L., Tsuchida, A., Zago, L., Schilling, S., Sigurdsson, S., Gottesman, R.F., Lewis, C.E., Aggarwal, N.T., Lopez, O.L., Smith, J.A., Valdés Hernández, M.C., Van der Grond, J., Wright, M.J., Knol, M.J., Dörr, M., Thomson, R.J., Bordes, C., Le Grand, Q., Duperron, M-G, Smith, A.V., Knopman, D.S., Schreiner, P.J., Evans, D.A., Rotter, J.I., Beiser, A.S., Maniega, S.M., Beekman, M., Trollor, J., Stott, D.J., Vernooij, M.W., Wittfeld, K., Niessen, W.J., Soumaré, A., Boerwinkle, E., Sidney, S., Turner, S.T., Davies, G., Thalamuthu, A., Völker, U., van Buchem, M.A., Bryan, R.N., Dupuis, J., Bastin, M.E., Ames, D., Teumer, A., Amouyel, P., Kwok, J.B., Bülow, R., Deary, I.J., Schofield, P.R., Brodaty, H., Jiang, J., Tabara, Y., Setoh, K., Miyamoto, S., Yoshida, K., Nagata, M., Kamatani, Y., Matsuda, F., Psaty, B.M., Bennett, D.A., De Jager, P.L., Mosley, T.H., Sachdev, P.S., Schmidt, R., Warren, H.R., Evangelou, E., Trégouët, D-A, Ikram, M.A., Wen, W., DeCarli, C., Srikanth, V.K., Jukema, J.W., Slagboom, E.P., Kardia, S.L.R., Okada, Y., Mazoyer, B., Wardlaw, J.M., Nyquist, P.A., Mather, K.A., Grabe, H.J., Schmidt, H., van Duijn, C.M., Gudnason, V., Longstreth, W.T., Launer, L. J., Lathrop, M., Seshadri, S., Tzourio, C., Adams, H.H., Matthews, P.M., Fornage, M., Debette, S., Sargurupremraj, M., Suzuki, H., Jian, X., Sarnowski, C., Evans, T.E., Bis, J.C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N.J., Hofer, E., Yanek, L.R., Hagenaars, S.P., Kumar, R.B., van den Akker, E.B., McWhirter, R.E., Trompet, S., Mishra, A., Saba, Y., Satizabal, C.L., Beaudet, G., Petit, L., Tsuchida, A., Zago, L., Schilling, S., Sigurdsson, S., Gottesman, R.F., Lewis, C.E., Aggarwal, N.T., Lopez, O.L., Smith, J.A., Valdés Hernández, M.C., Van der Grond, J., Wright, M.J., Knol, M.J., Dörr, M., Thomson, R.J., Bordes, C., Le Grand, Q., Duperron, M-G, Smith, A.V., Knopman, D.S., Schreiner, P.J., Evans, D.A., Rotter, J.I., Beiser, A.S., Maniega, S.M., Beekman, M., Trollor, J., Stott, D.J., Vernooij, M.W., Wittfeld, K., Niessen, W.J., Soumaré, A., Boerwinkle, E., Sidney, S., Turner, S.T., Davies, G., Thalamuthu, A., Völker, U., van Buchem, M.A., Bryan, R.N., Dupuis, J., Bastin, M.E., Ames, D., Teumer, A., Amouyel, P., Kwok, J.B., Bülow, R., Deary, I.J., Schofield, P.R., Brodaty, H., Jiang, J., Tabara, Y., Setoh, K., Miyamoto, S., Yoshida, K., Nagata, M., Kamatani, Y., Matsuda, F., Psaty, B.M., Bennett, D.A., De Jager, P.L., Mosley, T.H., Sachdev, P.S., Schmidt, R., Warren, H.R., Evangelou, E., Trégouët, D-A, Ikram, M.A., Wen, W., DeCarli, C., Srikanth, V.K., Jukema, J.W., Slagboom, E.P., Kardia, S.L.R., Okada, Y., Mazoyer, B., Wardlaw, J.M., Nyquist, P.A., Mather, K.A., Grabe, H.J., Schmidt, H., van Duijn, C.M., Gudnason, V., Longstreth, W.T., Launer, L. J., Lathrop, M., Seshadri, S., Tzourio, C., Adams, H.H., Matthews, P.M., Fornage, M., and Debette, S.

Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Published
2020

9. 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

10. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

Author

Aparicio H.J., Del C. Valdes Hernandez M., Luciano M., Liewald D., Deary I.J., Starr J.M., Bastin M.E., Maniega S.M., Slagboom P.E., Beekman M., Deelen J., Uh H.-W., Lemmens R., Brodaty H., Wright M.J., Ames D., Boncoraglio G.B., Hopewell J.C., Beecham A.H., Blanton S.H., Wright C.B., Sacco R.L., Wen W., Thalamuthu A., Armstrong N.J., Chong E., Schofield P.R., Kwok J.B., van der Grond J., Stott D.J., Ford I., Jukema J.W., Vernooij M.W., Hofman A., Uitterlinden A.G., van der Lugt A., Wittfeld K., Grabe H.J., Hosten N., von Sarnowski B., Volker U., Levi C., Jimenez-Conde J., Sharma P., Sudlow C.L.M., Rosand J., Woo D., Cole J.W., Meschia J.F., Slowik A., Thijs V., Lindgren A., Melander O., Grewal R.P., Rundek T., Rexrode K., Rothwell P.M., Arnett D.K., Jern C., Johnson J.A., Benavente O.R., Wasssertheil-Smoller S., Lee J.-M., Wong Q., Mitchell B.D., Rich S.S., McArdle P.F., Geerlings M.I., van der Graaf Y., de Bakker P.I.W., Asselbergs F.W., Srikanth V., Thomson R., McWhirter R., Moran C., Callisaya M., Phan T., Rutten-Jacobs L.C.A., Bevan S., Tzourio C., Mather K.A., Sachdev P.S., van Duijn C.M., Worrall B.B., Dichgans M., Kittner S.J., Markus H.S., Ikram M.A., Fornage M., Launer L.J., Seshadri S., Longstreth W.T., Debette S., Chauhan G., Adams H.H.H., Satizabal C.L., Bis J.C., Teumer A., Sargurupremraj M., Hofer E., Trompet S., Hilal S., Smith A.V., Jian X., Malik R., Traylor M., Pulit S.L., Amouyel P., Mazoyer B., Zhu Y.-C., Kaffashian S., Schilling S., Beecham G.W., Montine T.J., Schellenberg G.D., Kjartansson O., Gudnason V., Knopman D.S., Griswold M.E., Windham B.G., Gottesman R.F., Mosley T.H., Schmidt R., Saba Y., Schmidt H., Takeuchi F., Yamaguchi S., Nabika T., Kato N., Rajan K.B., Aggarwal N.T., De Jager P.L., Evans D.A., Psaty B.M., Rotter J.I., Rice K., Lopez O.L., Liao J., Chen C., Cheng C.-Y., Wong T.Y., Ikram M.K., van der Lee S.J., Amin N., Chouraki V., Destefano A.L., Romero J.R., Maillard P., Decarli C., Wardlaw J.M., Aparicio H.J., Del C. Valdes Hernandez M., Luciano M., Liewald D., Deary I.J., Starr J.M., Bastin M.E., Maniega S.M., Slagboom P.E., Beekman M., Deelen J., Uh H.-W., Lemmens R., Brodaty H., Wright M.J., Ames D., Boncoraglio G.B., Hopewell J.C., Beecham A.H., Blanton S.H., Wright C.B., Sacco R.L., Wen W., Thalamuthu A., Armstrong N.J., Chong E., Schofield P.R., Kwok J.B., van der Grond J., Stott D.J., Ford I., Jukema J.W., Vernooij M.W., Hofman A., Uitterlinden A.G., van der Lugt A., Wittfeld K., Grabe H.J., Hosten N., von Sarnowski B., Volker U., Levi C., Jimenez-Conde J., Sharma P., Sudlow C.L.M., Rosand J., Woo D., Cole J.W., Meschia J.F., Slowik A., Thijs V., Lindgren A., Melander O., Grewal R.P., Rundek T., Rexrode K., Rothwell P.M., Arnett D.K., Jern C., Johnson J.A., Benavente O.R., Wasssertheil-Smoller S., Lee J.-M., Wong Q., Mitchell B.D., Rich S.S., McArdle P.F., Geerlings M.I., van der Graaf Y., de Bakker P.I.W., Asselbergs F.W., Srikanth V., Thomson R., McWhirter R., Moran C., Callisaya M., Phan T., Rutten-Jacobs L.C.A., Bevan S., Tzourio C., Mather K.A., Sachdev P.S., van Duijn C.M., Worrall B.B., Dichgans M., Kittner S.J., Markus H.S., Ikram M.A., Fornage M., Launer L.J., Seshadri S., Longstreth W.T., Debette S., Chauhan G., Adams H.H.H., Satizabal C.L., Bis J.C., Teumer A., Sargurupremraj M., Hofer E., Trompet S., Hilal S., Smith A.V., Jian X., Malik R., Traylor M., Pulit S.L., Amouyel P., Mazoyer B., Zhu Y.-C., Kaffashian S., Schilling S., Beecham G.W., Montine T.J., Schellenberg G.D., Kjartansson O., Gudnason V., Knopman D.S., Griswold M.E., Windham B.G., Gottesman R.F., Mosley T.H., Schmidt R., Saba Y., Schmidt H., Takeuchi F., Yamaguchi S., Nabika T., Kato N., Rajan K.B., Aggarwal N.T., De Jager P.L., Evans D.A., Psaty B.M., Rotter J.I., Rice K., Lopez O.L., Liao J., Chen C., Cheng C.-Y., Wong T.Y., Ikram M.K., van der Lee S.J., Amin N., Chouraki V., Destefano A.L., Romero J.R., Maillard P., Decarli C., and Wardlaw J.M.

Abstract

Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10-8; and LINC00539/ZDHHC20, p = 5.82 x 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 x 10-25; p [SSBI] = 5.23 x 10-14 for hypertension), smoking (p[BI]= 4.4 x 10-10; p [SSBI] = 1.2 x 10 -4), diabetes (p[BI] = 1.7 x 10 -8; p [SSBI] = 2.8 x 10 -3), previous cardiovascular disease (p [BI] = 1.0 x 10-18; p [SSBI] = 2.3 x 10-7), stroke (p [BI] = 3.9 x 10-69; p [SSBI] = 3.2 x 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 x 10-157; p [SSBI] = 3.16 x 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p <= 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significa

Published
2019

11. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., Ikram, M.A., Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., and Ikram, M.A.

Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

12. 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., 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., 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, 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., 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., Lill, C.M., 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, 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.

Abstract

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary.

Published
2019

13. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, G., Adams, H.H.H., Satizabal, C.L., Bis, J.C., Teumer, A., Sargurupremraj, M., Hofer, E., Trompet, S., Hilal, S., Smith, A.V., Jian, X., Malik, R., Traylor, M., Pulit, S.L., Amouyel, P., Mazoyer, B., Zhu, Y-C, Kaffashian, S., Schilling, S., Beecham, G.W., Montine, T.J., Schellenberg, G.D., Kjartansson, O., Guðnason, V., Knopman, D.S., Griswold, M.E., Windham, B.G., Gottesman, R.F., Mosley, T.H., Schmidt, R., Saba, Y., Schmidt, H., Takeuchi, F., Yamaguchi, S., Nabika, T., Kato, N., Rajan, K.B., Aggarwal, N.T., De Jager, P.L., Evans, D.A., Psaty, B.M., Rotter, J.I., Rice, K., Lopez, O.L., Liao, J., Chen, C., Cheng, C-Y, Wong, T.Y., Ikram, M.K., van der Lee, S.J., Amin, N., Chouraki, V., DeStefano, A.L., Aparicio, H.J., Romero, J.R., Maillard, P., DeCarli, C., Wardlaw, J.M., Hernández, M.d.C.V., Luciano, M., Liewald, D., Deary, I.J., Starr, J.M., Bastin, M.E., Munoz Maniega, S., Slagboom, P.E., Beekman, M., Deelen, J., Uh, H-W, Lemmens, R., Brodaty, H., Wright, M.J., Ames, D., Boncoraglio, G.B., Hopewell, J.C., Beecham, A.H., Blanton, S.H., Wright, C.B., Sacco, R.L., Wen, W., Thalamuthu, A., Armstrong, N.J., Chong, E., Schofield, P.R., Kwok, J.B., Van der Grond, J., Stott, D.J., Ford, I., Jukema, J.W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., van der Lugt, A., Wittfeld, K., Grabe, H.J., Hosten, N., von Sarnowski, B., Völker, U., Levi, C., Jimenez-Conde, J., Sharma, P., Sudlow, C.L.M., Rosand, J., Woo, D., Cole, J.W., Meschia, J.F., Slowik, A., Thijs, V., Lindgren, A., Melander, O., Grewal, R.P., Rundek, T., Rexrode, K., Rothwell, P.M., Arnett, D.K., Jern, C., Johnson, J.A., Benavente, O.R., Wasssertheil-Smoller, S., Lee, J-M, Wong, Q., Mitchell, B.D., Rich, S.S., McArdle, P.F., Geerlings, M.I., van der Graaf, Y., de Bakker, P.I.W., Asselbergs, F.W., Srikanth, V., Thomson, R., McWhirter, R., Moran, C., Callisaya, M., Phan, T., Rutten-Jacobs, L.C.A., Bevan, S., Tzourio, C., Mather, K.A., Sachdev, P.S., van Duijn, C.M., Worrall, B.B., Dichgans, M., Kittner, S.J., Markus, H.S., Ikram, M.A., Fornage, M., Launer, L.J., Seshadri, S., Longstreth, W.T., Debette, S., Chauhan, G., Adams, H.H.H., Satizabal, C.L., Bis, J.C., Teumer, A., Sargurupremraj, M., Hofer, E., Trompet, S., Hilal, S., Smith, A.V., Jian, X., Malik, R., Traylor, M., Pulit, S.L., Amouyel, P., Mazoyer, B., Zhu, Y-C, Kaffashian, S., Schilling, S., Beecham, G.W., Montine, T.J., Schellenberg, G.D., Kjartansson, O., Guðnason, V., Knopman, D.S., Griswold, M.E., Windham, B.G., Gottesman, R.F., Mosley, T.H., Schmidt, R., Saba, Y., Schmidt, H., Takeuchi, F., Yamaguchi, S., Nabika, T., Kato, N., Rajan, K.B., Aggarwal, N.T., De Jager, P.L., Evans, D.A., Psaty, B.M., Rotter, J.I., Rice, K., Lopez, O.L., Liao, J., Chen, C., Cheng, C-Y, Wong, T.Y., Ikram, M.K., van der Lee, S.J., Amin, N., Chouraki, V., DeStefano, A.L., Aparicio, H.J., Romero, J.R., Maillard, P., DeCarli, C., Wardlaw, J.M., Hernández, M.d.C.V., Luciano, M., Liewald, D., Deary, I.J., Starr, J.M., Bastin, M.E., Munoz Maniega, S., Slagboom, P.E., Beekman, M., Deelen, J., Uh, H-W, Lemmens, R., Brodaty, H., Wright, M.J., Ames, D., Boncoraglio, G.B., Hopewell, J.C., Beecham, A.H., Blanton, S.H., Wright, C.B., Sacco, R.L., Wen, W., Thalamuthu, A., Armstrong, N.J., Chong, E., Schofield, P.R., Kwok, J.B., Van der Grond, J., Stott, D.J., Ford, I., Jukema, J.W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., van der Lugt, A., Wittfeld, K., Grabe, H.J., Hosten, N., von Sarnowski, B., Völker, U., Levi, C., Jimenez-Conde, J., Sharma, P., Sudlow, C.L.M., Rosand, J., Woo, D., Cole, J.W., Meschia, J.F., Slowik, A., Thijs, V., Lindgren, A., Melander, O., Grewal, R.P., Rundek, T., Rexrode, K., Rothwell, P.M., Arnett, D.K., Jern, C., Johnson, J.A., Benavente, O.R., Wasssertheil-Smoller, S., Lee, J-M, Wong, Q., Mitchell, B.D., Rich, S.S., McArdle, P.F., Geerlings, M.I., van der Graaf, Y., de Bakker, P.I.W., Asselbergs, F.W., Srikanth, V., Thomson, R., McWhirter, R., Moran, C., Callisaya, M., Phan, T., Rutten-Jacobs, L.C.A., Bevan, S., Tzourio, C., Mather, K.A., Sachdev, P.S., van Duijn, C.M., Worrall, B.B., Dichgans, M., Kittner, S.J., Markus, H.S., Ikram, M.A., Fornage, M., Launer, L.J., Seshadri, S., Longstreth, W.T., and Debette, S.

Abstract

Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10−8; and LINC00539/ZDHHC20, p = 5.82 × 10−9. Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10−25; p[SSBI] = 5.23 × 10−14 for hypertension), smoking (p[BI] = 4.4 × 10−10; p[SSBI] = 1.2 × 10−4), diabetes (p[BI] = 1.7 × 10−8; p[SSBI] = 2.8 × 10−3), previous cardiovascular disease (p[BI] = 1.0 × 10−18; p[SSBI] = 2.3 × 10−7), stroke (p[BI] = 3.9 × 10−69; p[SSBI] = 3.2 × 10−24), and MRI-defined white matter hyperintensity burden (p[BI] = 1.43 × 10−157; p[SSBI] = 3.16 × 10−106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifi

Published
2019

15. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Author

Sims, R., van der Lee, S.J., Naj, A.C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B.W., Boland, A., Raybould, R., Bis, J.C., Martin, E.R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A.B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R.R., Olaso, R., Hoffmann, P., Grove, M.L., Vardarajan, B.N., Hiltunen, M., Nöthen, M.M., White, C.C., Hamilton-Nelson, K.L., Epelbaum, J., Maier, W., Choi, S.H., Beecham, G.W., Dulary, C., Herms, S., Smith, A.V., Funk, C.C., Derbois, Forstner, A.J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C.L., Valladares, O., Squassina, A., Thomas, R., Brody, J.A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F.J., Zhao, Y., Garcia, F.S., Denning, N., Fornage, M., Malamon, J., Naranjo, M.C.D., Majounie, E., Mosley, T.H., Dombroski, B., Wallon, D., Lupton, M.K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L.B., Panza, F., McGuinness, B., Moreno-Grau, S., Burgess, J.D., Solfrizzi, V., Proitsi, P., Adams, H.H., Allen, M., Seripa, D., Pastor, P., Cupples, L.A., Price, N.D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A.S., Giedraitis, V., Hampel, H., Garcia, M.E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P.K., Pasquier, F., Boccardi, V., Henández, I., Barber, R.C., Scherer, M., Tarraga, L., Adams, P.M., Leber, M., Chen, Y., Albert, M.S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, C., Schmidt, H., Doody, R.S., Spalletta, G., Longstreth, W.T., Jr., Fairchild, T.J., Bossù, P., Lopez, O.L., Frosch, M.P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R.M., Jessen, F., Li, S., Kamboh, M.I., Morris, J., Sotolongo-Grau, O., Katz, M.J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M.D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J.T., Lord, J., Turton, J., Hartmann, A.M., Cecchetti, R., Fenoglio, C., Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M.D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I.S., Brookes, K., Cupidi, C., Maletta, R.G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N.C., Hardy, J., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barnes, L.L., Barral, S., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Burns, J.M., Buxbaum, J.D., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Diaz, C.C., Chui, H.C., Clark, D.G., Cribbs, D.H., Crocco, E.A., DeCarli, C., Dick, M., Duara, R., Evans, D.A., Faber, K.M., Fallon, K.B., Fardo, D.W., Farlow, M.R., Ferris, S., Foroud, T.M., Galasko, D.R., Gearing, M., Geschwind, D.H., Gilbert, J.R., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hamilton, R.L., Harrell, L.E., Honig, L.S., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Abner, E., Jin, L.W., Jun, G., Karydas, A., Kaye, J.A., Kim, R., Kowall, N.W., Kramer, J.H., LaFerla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Li, G., Lieberman, A.P., Lunetta, K.L., Lyketsos, C.G., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., McCormick, W.C., McCurry, S.M., McDavid, A.N., McKee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Paulson, H.L., Perry, W., Peskind, E., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Sager, M.A., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Swerdlow, R.H., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Van Deerlin, V.M., Van Eldik, L.J., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Wilhelmsen, K.C., Williamson, J., Wingo, T.S., Woltjer, R.L., Wright, C.B., Yu, C.E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P.P., Fernadez, C.M., Benito, Y.A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A.M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J.J., Keene, C.D., Tschanz, J., Fitzpatrick, A.L., Kukull, W.A., Norton, M., Aspelund, T., Larson, E.B., Munger, R., Rotter, J.I., Lipton, R.B., Bullido, M.J., Hofman, A., Montine, T.J., Coto, E., Boerwinkle, E., Petersen, R.C., Alvarez, V., Rivadeneira, F., Reiman, E.M., Gallo, M., O'Donnell, C.J., Reisch, J.S., Bruni, A.C., Royall, D.R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D.W., Mancuso, M., Bonuccelli, U., Winslow, A.R., Daniele, A., Wu, C.K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D.C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C.E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M.C., Owen, M.J., Behrens, T.W., Mead, S., Goate, A.M., Uitterlinden, A.G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D.A., Powell, J., Golde, T.E., Graff, C., De Jager, P.L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B.M., Passmore, P., Younkin, S.G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D.W., Dartigues, J.F., DeStefano, A.L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J.K., Farrer, L.A., Van Broeckhoven, C., Ikram, M.A., Jones, L., Haines, J.L., Tzourio, C., Launer, L.J., Escott-Price, V., Mayeux, R., Deleuze, J.F., Amin, N., Holmans, P.A., Pericak-Vance, M.A., Amouyel, P., van Duijn, C.M., Ramirez, A., Wang, L.S., Lambert, J.C., Seshadri, S., Williams, J., Schellenberg, G.D., Peloso, Gina M., van der Lee, Sven J., Destefano, Anita L., and Seshardi, Sudha

Published
2018
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16. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe, P. Depondt, C. Dlugos, D. Ferraro, T.N. French, J. Hjalgrim, H. Jamnadas-Khoda, J. Kälviäinen, R. Kunz, W.S. Lerche, H. Leu, C. Lindhout, D. Lo, W. Lowenstein, D. McCormack, M. Møller, R.S. Molloy, A. Ng, P.-W. Oliver, K. Privitera, M. Radtke, R. Ruppert, A.-K. Sander, T. Schachter, S. Schankin, C. Scheffer, I. Schoch, S. Sisodiya, S.M. Smith, P. Sperling, M. Striano, P. Surges, R. Neil Thomas, G. Visscher, F. Whelan, C.D. Zara, F. Heinzen, E.L. Marson, A. Becker, F. Stroink, H. Zimprich, F. Gasser, T. Gibbs, R. Heutink, P. Martinez, M. Morris, H.R. Sharma, M. Ryten, M. Mok, K.Y. Pulit, S. Bevan, S. Holliday, E. Attia, J. Battey, T. Boncoraglio, G. Thijs, V. Chen, W.-M. Mitchell, B. Rothwell, P. Sharma, P. Sudlow, C. Vicente, A. Markus, H. Kourkoulis, C. Pera, J. Raffeld, M. Silliman, S. Perica, V.B. Thornton, L.M. Huckins, L.M. William Rayner, N. Lewis, C.M. Gratacos, M. Rybakowski, F. Keski-Rahkonen, A. Raevuori, A. Hudson, J.I. Reichborn-Kjennerud, T. Monteleone, P. Karwautz, A. Mannik, K. Baker, J.H. O'Toole, J.K. Trace, S.E. Davis, O.S.P. Helder, S.G. Ehrlich, S. Herpertz-Dahlmann, B. Danner, U.N. Van Elburg, A.A. Clementi, M. Forzan, M. Docampo, E. Lissowska, J. Hauser, J. Tortorella, A. Maj, M. Gonidakis, F. Tziouvas, K. Papezova, H. Yilmaz, Z. Wagner, G. Cohen-Woods, S. Herms, S. Julia, A. Rabionet, R. Dick, D.M. Ripatti, S. Andreassen, O.A. Espeseth, T. Lundervold, A.J. Steen, V.M. Pinto, D. Scherer, S.W. Aschauer, H. Schosser, A. Alfredsson, L. Padyukov, L. Halmi, K.A. Mitchell, J. Strober, M. Bergen, A.W. Kaye, W. Szatkiewicz, J.P. Cormand, B. Ramos-Quiroga, J.A. Sánchez-Mora, C. Ribasés, M. Casas, M. Hervas, A. Arranz, M.J. Haavik, J. Zayats, T. Johansson, S. Williams, N. Dempfle, A. Rothenberger, A. Kuntsi, J. Oades, R.D. Banaschewski, T. Franke, B. Buitelaar, J.K. Vasquez, A.A. Doyle, A.E. Reif, A. Lesch, K.-P. Freitag, C. Rivero, O. Palmason, H. Romanos, M. Langley, K. Rietschel, M. Witt, S.H. Dalsgaard, S. Børglum, A.D. Waldman, I. Wilmot, B. Molly, N. Bau, C.H.D. Crosbie, J. Schachar, R. Loo, S.K. McGough, J.J. Grevet, E.H. Medland, S.E. Robinson, E. Weiss, L.A. Bacchelli, E. Bailey, A. Bal, V. Battaglia, A. Betancur, C. Bolton, P. Cantor, R. Celestino-Soper, P. Dawson, G. De Rubeis, S. Duque, F. Green, A. Klauck, S.M. Leboyer, M. Levitt, P. Maestrini, E. Mane, S. Moreno-De-Luca, D. Parr, J. Regan, R. Reichenberg, A. Sandin, S. Vorstman, J. Wassink, T. Wijsman, E. Cook, E. Santangelo, S. Delorme, R. Roge, B. Magalhaes, T. Arking, D. Schulze, T.G. Thompson, R.C. Strohmaier, J. Matthews, K. Melle, I. Morris, D. Blackwood, D. McIntosh, A. Bergen, S.E. Schalling, M. Jamain, S. Maaser, A. Fischer, S.B. Reinbold, C.S. Fullerton, J.M. Guzman-Parra, J. Mayoral, F. Schofield, P.R. Cichon, S. Mühleisen, T.W. Degenhardt, F. Schumacher, J. Bauer, M. Mitchell, P.B. Gershon, E.S. Rice, J. Potash, J.B. Zandi, P.P. Craddock, N. Nicol Ferrier, I. Alda, M. Rouleau, G.A. Turecki, G. Ophoff, R. Pato, C. Anjorin, A. Stahl, E. Leber, M. Czerski, P.M. Cruceanu, C. Jones, I.R. Posthuma, D. Andlauer, T.F.M. Forstner, A.J. Streit, F. Baune, B.T. Air, T. Sinnamon, G. Wray, N.R. MacIntyre, D.J. Porteous, D. Homuth, G. Rivera, M. Grove, J. Middeldorp, C.M. Hickie, I. Pergadia, M. Mehta, D. Smit, J.H. Jansen, R. De Geus, E. Dunn, E. Li, Q.S. Nauck, M. Schoevers, R.A. Beekman, A.T.F. Knowles, J.A. Viktorin, A. Arnold, P. Barr, C.L. Bedoya-Berrio, G. Joseph Bienvenu, O. Brentani, H. Burton, C. Camarena, B. Cappi, C. Cath, D. Cavallini, M. Cusi, D. Darrow, S. Denys, D. Derks, E.M. Dietrich, A. Fernandez, T. Figee, M. Freimer, N. Gerber, G. Grados, M. Greenberg, E. Hanna, G.L. Hartmann, A. Hirschtritt, M.E. Hoekstra, P.J. Huang, A. Huyser, C. Illmann, C. Jenike, M. Kuperman, S. Leventhal, B. Lochner, C. Lyon, G.J. Macciardi, F. Madruga-Garrido, M. Malaty, I.A. Maras, A. McGrath, L. Miguel, E.C. Mir, P. Nestadt, G. Nicolini, H. Okun, M.S. Pakstis, A. Paschou, P. Piacentini, J. Pittenger, C. Plessen, K. Ramensky, V. Ramos, E.M. Reus, V. Richter, M.A. Riddle, M.A. Robertson, M.M. Roessner, V. Rosário, M. Samuels, J.F. Sandor, P. Stein, D.J. Tsetsos, F. Van Nieuwerburgh, F. Weatherall, S. Wendland, J.R. Wolanczyk, T. Worbe, Y. Zai, G. Goes, F.S. McLaughlin, N. Nestadt, P.S. Grabe, H.-J. Depienne, C. Konkashbaev, A. Lanzagorta, N. Valencia-Duarte, A. Bramon, E. Buccola, N. Cahn, W. Cairns, M. Chong, S.A. Cohen, D. Crespo-Facorro, B. Crowley, J. Davidson, M. DeLisi, L. Dinan, T. Donohoe, G. Drapeau, E. Duan, J. Haan, L. Hougaard, D. Karachanak-Yankova, S. Khrunin, A. Klovins, J. Kučinskas, V. Keong, J.L.C. Limborska, S. Loughland, C. Lönnqvist, J. Maher, B. Mattheisen, M. McDonald, C. Murphy, K.C. Nenadic, I. Van Os, J. Pantelis, C. Pato, M. Petryshen, T. Quested, D. Roussos, P. Sanders, A.R. Schall, U. Schwab, S.G. Sim, K. So, H.-C. Stögmann, E. Subramaniam, M. Toncheva, D. Waddington, J. Walters, J. Weiser, M. Cheng, W. Cloninger, R. Curtis, D. Gejman, P.V. Henskens, F. Mattingsdal, M. Oh, S.-Y. Scott, R. Webb, B. Breen, G. Churchhouse, C. Bulik, C.M. Daly, M. Dichgans, M. Faraone, S.V. Guerreiro, R. Holmans, P. Kendler, K.S. Koeleman, B. Mathews, C.A. Price, A. Scharf, J. Sklar, P. Williams, J. Wood, N.W. Cotsapas, C. Palotie, A. Smoller, J.W. Sullivan, P. Rosand, J. Corvin, A. Neale, B.M. The Brainstorm Consortium

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

Published
2018

17. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author

Vojinovic, D., Adams, H.H., Jian, X., Yang, Q., Smith, A.V., Bis, J.C., Teumer, A., Scholz, M., Armstrong, N.J., Hofer, E., Saba, Y., Luciano, M., Bernard, M., Trompet, S., Yang, J., Gillespie, N.A., van der Lee, S.J., Neumann, A., Ahmad, S., Andreassen, O.A., Ames, D., Amin, N., Arfanakis, K., Bastin, M.E., Becker, D.M., Beiser, A.S., Beyer, F., Brodaty, H., Bryan, R.N., Bülow, R., Dale, A.M., De Jager, P.L., Deary, I.J., DeCarli, C., Fleischman, D.A., Gottesman, R.F., Van der Grond, J., Gudnason, V., Harris, T.B., Homuth, G., Knopman, D.S., Kwok, J.B., Lewis, C.E., Li, S., Loeffler, M., Lopez, O.L., Maillard, P., El Marroun, H., Mather, K.A., Mosley, T.H., Muetzel, R.L., Nauck, M., Nyquist, P.A., Panizzon, M.S., Pausova, Z., Psaty, B.M., Rice, K., Rotter, J.I., Royle, N., Satizabal, C.L., Schmidt, R., Schofield, P.R., Schreiner, P.J., Sidney, S., Stott, D.J., Thalamuthu, A., Uitterlinden, A.G., Valdés Hernández, M.C., Vernooij, M.W., Wen, W., White, T., Witte, A.V., Wittfeld, K., Wright, M.J., Yanek, L.R., Tiemeier, H., Kremen, W.S., Bennett, D.A., Jukema, J.W., Paus, T., Wardlaw, J.M., Schmidt, H., Sachdev, P.S., Villringer, A., Grabe, H.J., Longstreth, W.T., van Duijn, C.M., Launer, L.J., Seshadri, S., Ikram, M.A., Fornage, M., Vojinovic, D., Adams, H.H., Jian, X., Yang, Q., Smith, A.V., Bis, J.C., Teumer, A., Scholz, M., Armstrong, N.J., Hofer, E., Saba, Y., Luciano, M., Bernard, M., Trompet, S., Yang, J., Gillespie, N.A., van der Lee, S.J., Neumann, A., Ahmad, S., Andreassen, O.A., Ames, D., Amin, N., Arfanakis, K., Bastin, M.E., Becker, D.M., Beiser, A.S., Beyer, F., Brodaty, H., Bryan, R.N., Bülow, R., Dale, A.M., De Jager, P.L., Deary, I.J., DeCarli, C., Fleischman, D.A., Gottesman, R.F., Van der Grond, J., Gudnason, V., Harris, T.B., Homuth, G., Knopman, D.S., Kwok, J.B., Lewis, C.E., Li, S., Loeffler, M., Lopez, O.L., Maillard, P., El Marroun, H., Mather, K.A., Mosley, T.H., Muetzel, R.L., Nauck, M., Nyquist, P.A., Panizzon, M.S., Pausova, Z., Psaty, B.M., Rice, K., Rotter, J.I., Royle, N., Satizabal, C.L., Schmidt, R., Schofield, P.R., Schreiner, P.J., Sidney, S., Stott, D.J., Thalamuthu, A., Uitterlinden, A.G., Valdés Hernández, M.C., Vernooij, M.W., Wen, W., White, T., Witte, A.V., Wittfeld, K., Wright, M.J., Yanek, L.R., Tiemeier, H., Kremen, W.S., Bennett, D.A., Jukema, J.W., Paus, T., Wardlaw, J.M., Schmidt, H., Sachdev, P.S., Villringer, A., Grabe, H.J., Longstreth, W.T., van Duijn, C.M., Launer, L.J., Seshadri, S., Ikram, M.A., and Fornage, M.

Abstract

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = −0.59, p-value = 3.14 × 10−6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.

Published
2018

18. 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

19. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., Kiel, D.P., Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., and Kiel, D.P.

Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10(-8)) or suggestively genome wide (p < 2.3 × 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Published
2017

20. Novel genetic loci associated with hippocampal volume

Author

Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., Ikram, M.A., Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., and Ikram, M.A.

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017

21. A novel Alzheimer disease locus located near the gene encoding tau protein

Author

Jun, G., Ibrahim-Verbaas, C.A., Vronskaya, M., Lambert, J.-., Chung, J., Naj, A.C., Kunkle, B.W., Wang, L.-., Bis, J.C., Bellenguez, C., Harold, D., Lunetta, K.L., Destefano, A.L., Grenier-Boley, B., Sims, R., Beecham, G.W., Smith, A.V., Chouraki, V., Hamilton-Nelson, K.L., Ikram, M.A., Fievet, N., Denning, N., Martin, E.R., Schmidt, H., Kamatani, Y., Dunstan, M.L., Valladares, O., Laza, A.R., Zelenika, D., Ramirez, A., Foroud, T.M., Choi, S.-., Boland, A., Becker, T., Kukull, W.A., Van Der Lee, S.J., Pasquier, F., Cruchaga, C., Beekly, D., Fitzpatrick, A.L., Hanon, O., Gill, M., Barber, R., Gudnason, V., Campion, D., Love, S., Bennett, D.A., Amin, N., Berr, C., Tsolaki, M., Buxbaum, J.D., Lopez, O.L., Deramecourt, V., Fox, N.C., Cantwell, L.B., Tárraga, L., Dufouil, C., Hardy, J., Crane, P.K., Eiriksdottir, G., Hannequin, D., Clarke, R., Evans, D., Mosley, T.H., Letenneur, L., Brayne, C., Maier, W., De Jager, P., Emilsson, V., Dartigues, J.-., Hampel, H., Kamboh, M.I., De Bruijn, R.F.A.G., Tzourio, C., Pastor, P., Larson, E.B., Rotter, J.I., O'Donovan, M.C., Montine, T.J., Nalls, M.A., Mead, S., Reiman, E.M., Jonsson, P.V., Holmes, C., St George-Hyslop, P.H., Boada, M., Passmore, P., Wendland, J.R., Schmidt, R., Morgan, K., Winslow, A.R., Powell, J.F., Carasquillo, M., Younkin, S.G., Jakobsdóttir, J., Kauwe, J.S.K., Wilhelmsen, K.C., Rujescu, D., Nöthen, M.M., Hofman, A., Jones, L., Haines, J.L., Psaty, B.M., Van Broeckhoven, C., Holmans, P., Launer, L.J., Mayeux, R., Lathrop, M., Goate, A.M., Escott-Price, V., Seshadri, S., Pericak-Vance, M.A., Amouyel, P., Williams, J., Van Duijn, C.M., Schellenberg, G.D., Farrer, L.A., Adams, P.M., Albert, M.S., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barmada, M.M., Barnes, L.L., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Blacker, D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Chui, H.C., Clark, D.G., Corneveaux, J., Cribbs, D.H., Crocco, E.A., De Jager, P.L., Decarli, C., Dekosky, S.T., Yesim Demirci, F., Dick, M., Dickson, D.W., Doody, R.S., Duara, R., Ertekin-Taner, N., Faber, K.M., Fairchild, T.J., Fallon, K.B., Farlow, M.R., Ferris, S., Frosch, M.P., Galasko, D.R., Gearing, M., Geschwind, D.H., Ghetti, B., Gilbert, J.R., Glass, J.D., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hakonarson, H., Hamilton, R.L., Harrell, L.E., Head, E., Honig, L.S., Huebinger, R.M., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Jicha, G.A., Jin, L., Karydas, A., Kaye, J.A., Kim, R., Koo, E.H., Kowall, N.W., Kramer, J.H., Laferla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Ge, L., Lieberman, A.P., Lin, C., Lyketsos, C.G., Mack, W.J., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., Mccormick, W.C., Mccurry, S.M., Mcdavid, A.N., Mckee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Mukherjee, S., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Partch, A., Paulson, H.L., Perry, W., Peskind, E., Petersen, R.C., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reisch, J.S., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Royall, D.R., Sager, M.A., Sano, M., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Tsuang, D.W., Van Deerlin, V.M., Van Eldik, L.J., Vardarajan, B.N., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Williamson, J., Wishnek, S., Woltjer, R.L., Wright, C.B., Chuang-Kuo, W., Chang-En, Y., Lei, Y., Thomas, C., Gerrish, A., Chapman, J., Stretton, A., Morgan, A., Oldham, H., Owen, M.J., Kehoe, P.G., Medway, C., Brown, K., Lord, J., Turton, J., Hooper, N.M., Vardy, E., Warren, J.D., Schott, J.M., Uphill, J., Hollingworth, P., Ryan, N., Rossor, M., Collinge, J., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffmann, P., Kornhuber, J., Wei, G., Feulner, T., Mayhaus, M., Pichler, S., Riemenschneider, M., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A.D., Warden, D., Wilcock, G., Heuser, I., Wiltfang, J., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N.J., Gurling, H., Mcquillin, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Shaw, C.E., Singleton, A.B., Guerreiro, R., Russo, G., Jöckel, K., Moebus, S., Klopp, N., Wichmann, H.-., Li, M., Bisceglio, G., Fisher, E., Warner, N., Pickering-Brown, S., Craig, D., Johnston, J.A., Mcguinness, B., Todd, S., Rubinsztein, D.C., Lovestone, S., Bayer, A., Gallacher, J., Proitsi, P., Ortega-Cubero, Saraadams, P., Albert, M., Albin, R., Apostolova, L., Arnold, S., Atwood, C., Baldwin, C., Barmada, M., Barnes, L., Beach, T., Becker, J., Bigio, E., Bird, T., Boeve, B., Bowen, J., Burke, J., Cairns, N., Carlson, C., Carlsson, C., Carney, R., Carrasquillo, M., Carroll, S., Chui, H., Clark, D., Cribbs, D., Crocco, E., De Jager PL, Dekosky, S., Demirci, F., Dickson, D., Doody, R., Faber, K., Fairchild, T., Fallon, K., Farlow, M., Frosch, M., Galasko, D., Geschwind, D., Gilbert, J., Glass, J., Graff-Radford, N., Green, R., Growdon, J., Hamilton, R., Harrell, L., Honig, L., Huebinger, R., Huentelman, M., Hulette, C., Hyman, B., Jarvik, G., Jicha, G., Kauwe, J., Kaye, J., Koo, E., Kowall, N., Kramer, J., Laferla, F., Lah, J., Leverenz, J., Levey, A., Li, G., Lieberman, A., Lopez, O., Lyketsos, C., Mack, W., Marson, D., Mash, D., Mccormick, W., Mccurry, S., Mcdavid, A., Mckee, A., Miller, B., Miller, C., Miller, J., Morris, J., Murrell, J., Myers, A., Olichney, J., Pankratz, V., Parisi, J., Paulson, H., Petersen, R., Poon, W., Quinn, J., Reisch, J., Ringman, J., Roberson, E., Rosen, H., Rosenberg, R., Royall, D., Sager, M., Saykin, A., Schneider, J., Schneider, L., Seeley, W., Smith, A., Sonnen, J., Stern, R., Tanzi, R., Thornton-Wells, T., Trojanowski, J., Troncoso, J., Tsuang, D., Van Deerlin VM, Van Eldik LJ, Vardarajan, B., Vinters, H., Vonsattel, J., Welsh-Bohmer, K., Woltjer, R., Wright, C., Wu, C., Yu, C., Yu, L., Au, R., Wolf, P., Beiser, A., Satizabal, C., Uitterlinden, A., Rivadeneira, F., Koudstaal, P., Longstreth WT Jr, Kuller, L., Lumley, T., Rice, K., Harris, T., Nalls, M., Marksteiner, J., Dal-Bianco, P., Töglhofer, A., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A., Boerwinkle, E., Bressler, J., Fornage, M., Morón, F., Hernández, I., Roca, M., Mauleón, A., Alegret, M., Ramírez-Lorca, R., González-Perez, A., Alpérovitch, A., Alvarez, V., Barberger-Gateau, P., Bettens, K., Bossù, P., Brice, A., Bullido, M., Caffara, P., Clarimon, J., Combarros, O., Coto, E., Del Zampo, M., Delepine, M., Deniz Naranjo MC, Epelbaum, J., Fratiglioni, L., Galimberti, D., Graff, C., Hiltunen, M., Ingelsson, M., Keller, L., Lannfelt, L., Llèo, A., Mancuso, M., Mateo, I., Mecocci, P., Nacmias, B., Panza, F., Pilotto, A., Garcia, F., Scarpini, E., Seripa, D., Sleegers, K., Soininen, H., Sorbi, S., Spalletta, G., Wallon, D., Owen, M., Kehoe, P., Hooper, N., Warren, J., Schott, J., Gu, W., Bass, N., Shaw, C., Singleton, A., Wichmann, H., Ma, L., Johnston, J., Rubinsztein, D., Ortega-Cubero, S., Epidemiology, Neurology, and Internal Medicine

Subjects
0301 basic medicine, Apolipoprotein E, Apolipoprotein E4, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, genetics [Alzheimer Disease], MAPT protein, human, tau Proteins, Polymorphism, Single Nucleotide, Article, Chromosomes, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Settore BIO/13 - Biologia Applicata, Humans, ddc:610, Polymorphism, Molecular Biology, Biology, genetics [Apolipoprotein E4], Genetic association, Temporal cortex, Genetics, Pair 17, Haplotype, Single Nucleotide, 3. Good health, Chromosome 17 (human), genetics [tau Proteins], Chemistry, 030104 developmental biology, Psychiatry and Mental Health, Chromosomes, Human, Pair 17, Genome-Wide Association Study, Settore MED/26 - Neurologia, Human medicine, Psychology, 030217 neurology & neurosurgery, Human
Abstract

APOE epsilon 4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE epsilon 4+ (10 352 cases and 9207 controls) and APOE epsilon 4 - (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE e4 status. Suggestive associations (P < 1x10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE epsilon 4+: 1250 cases and 536 controls; APOE epsilon 4 -: 718 cases and 1699 controls). Among APOE epsilon 4 - subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P = 5.8 x 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE epsilon 4+ subjects (CR1 and CLU) or APOE epsilon 4 - subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P = 1.6 x 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P

Published
2016

22. A molecular network of the aging brain implicatesINPPL1andPLXNB1in Alzheimer’s disease

Author

Mostafavi, S., primary, Gaiteri, C., additional, Sullivan, S. E., additional, White, C.C., additional, Tasaki, S., additional, Xu, J., additional, Taga, M., additional, Klein, H., additional, Patrick, E., additional, Komashko, V., additional, McCabe, C., additional, Smith, R., additional, Bradshaw, E.B., additional, Root, D., additional, Regev, A., additional, Yu, L., additional, Chibnik, L.B., additional, Schneider, J.A., additional, Young-Pearse, T., additional, Bennett, D.A., additional, and De Jager, P.L., additional

Published
2017
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23. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author

Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., Thompson, P.M., Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., and Thompson, P.M.

Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Published
2016

24. Correction: The influence of age and sex on genetic associations with adult body size and shape : a large-scale genome-wide interaction study.

Author

Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., Loos, R.J., Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., and Loos, R.J.

Abstract

This corrects the article DOI: 10.1371/journal.pgen.1005378.

Published
2016

25. Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium

Author

Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Deary, I.J. (Ian), Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), and Deary, I.J. (Ian)

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10-9, MIR2113; rs17522122, P=2.55 × 10-8, AKAP6; rs10119, P=5.67 × 10-9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ∼1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10-17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015
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26. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., van der Lee, S.J., Le Hellard, S., Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., De Jager, P.L., Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Scotland, Generation, Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R, Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., van Swieten, J.C., Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A, Brodaty, H., de Craen, A.J.M., Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L-G, Porteous, D.J., Räikkönen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., van Duijn, C, Launer, L., Fitzpatrick, A.L., Seshadri, S., Mosley, T.H., Deary, I.J., Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., van der Lee, S.J., Le Hellard, S., Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., De Jager, P.L., Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Scotland, Generation, Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R, Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., van Swieten, J.C., Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A, Brodaty, H., de Craen, A.J.M., Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L-G, Porteous, D.J., Räikkönen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., van Duijn, C, Launer, L., Fitzpatrick, A.L., Seshadri, S., Mosley, T.H., and Deary, I.J.

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015

27. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

Author

Goris, A., van Setten, J., Diekstra, F., Ripke, S., Patsopoulos, N.A., Sawcer, S.J., van Es, M., Andersen, P.M., Melki, J., Meininger, V., Hardiman, O., Landers, J.E., Brown, R.H., Shatunov, A., Leigh, N., Al-Chalabi, A., Shaw, C.E., Traynor, B.J., Chio, A., Restagno, G., Mora, G., Ophoff, R.A., Oksenberg, J.R., Van Damme, P., Compston, A., Robberecht, W., Dubois, B., van den Berg, L.H., De Jager, P.L., Veldink, J.H., de Bakker, P.I.W., Kermode, A.G., Goris, A., van Setten, J., Diekstra, F., Ripke, S., Patsopoulos, N.A., Sawcer, S.J., van Es, M., Andersen, P.M., Melki, J., Meininger, V., Hardiman, O., Landers, J.E., Brown, R.H., Shatunov, A., Leigh, N., Al-Chalabi, A., Shaw, C.E., Traynor, B.J., Chio, A., Restagno, G., Mora, G., Ophoff, R.A., Oksenberg, J.R., Van Damme, P., Compston, A., Robberecht, W., Dubois, B., van den Berg, L.H., De Jager, P.L., Veldink, J.H., de Bakker, P.I.W., and Kermode, A.G.

Abstract

Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.

Published
2014

28. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

Author

LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., Koellinger, P.D., LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., and Koellinger, P.D.

Abstract

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

Published
2013

29. Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Author

Wang, J.H., Pappas, D., De Jager, P.L., Pelletier, D., de Bakker, P.I.W., Kappos, L., Polman, C.H., Chibnik, L.B., Hafler, D.A., Matthews, P.M., Hauser, S.L., Baranzini, S.E., Oksenberg, J.R., Kermode, A.G., Wang, J.H., Pappas, D., De Jager, P.L., Pelletier, D., de Bakker, P.I.W., Kappos, L., Polman, C.H., Chibnik, L.B., Hafler, D.A., Matthews, P.M., Hauser, S.L., Baranzini, S.E., Oksenberg, J.R., and Kermode, A.G.

Abstract

BACKGROUND: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. METHODS: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. RESULTS: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the othe

Published
2011

30. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Author

Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C.C.A., Patsopoulos, N.A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S.E., Edkins, S., Gray, E., Booth, D.R., Potter, S.C., Goris, A., Band, G., Bang Oturai, A., Strange, A., Saarela, J., Bellenguez, C., Fontaine, B., Gillman, M., Hemmer, B., Gwilliam, R., Zipp, F., Jayakumar, A., Martin, R., Leslie, S., Hawkins, S., Giannoulatou, E., D’alfonso, S., Blackburn, H., Martinelli Boneschi, F., Liddle, J., Harbo, H.F., Perez, M.L., Spurkland, A., Waller, M.J., Mycko, M.P., Ricketts, M., Comabella, M., Hammond, N., Kockum, I., McCann, O.T., Ban, M., Whittaker, P., Kemppinen, A., Weston, P., Hawkins, C., Widaa, S., Zajicek, J., Dronov, S., Robertson, N., Bumpstead, S.J., Barcellos, L.F., Ravindrarajah, R., Abraham, R., Alfredsson, L., Ardlie, K., Aubin, C., Baker, A., Baker, K., Baranzini, S.E., Bergamaschi, L., Bergamaschi, R., Bernstein, A., Berthele, A., Boggild, M., Bradfield, J.P., Brassat, D., Broadley, S.A., Buck, D., Butzkueven, H., Capra, R., Carroll, W.M., Cavalla, P., Celius, E.G., Cepok, S., Chiavacci, R., Clerget-Darpoux, F., Clysters, K., Comi, G., Cossburn, M., Cournu-Rebeix, I., Cox, M.B., Cozen, W., Cree, B.A.C., Cross, A.H., Cusi, D., Daly, M.J., Davis, E., de Bakker, P.I.W., Debouverie, M., D’hooghe, M.B., Dixon, K., Dobosi, R., Dubois, B., Ellinghaus, D., Elovaara, I., Esposito, F., Fontenille, C., Foote, S., Franke, A., Galimberti, D., Ghezzi, A., Glessner, J., Gomez, R., Gout, O., Graham, C., Grant, S.F.A., Rosa Guerini, F., Hakonarson, H., Hall, P., Hamsten, A., Hartung, H-P, Heard, R.N., Heath, S., Hobart, J., Hoshi, M., Infante-Duarte, C., Ingram, G., Ingram, W., Islam, T., Jagodic, M., Kabesch, M., Kermode, A.G., Kilpatrick, T.J., Kim, C., Klopp, N., Koivisto, K., Larsson, M., Lathrop, M., Lechner-Scott, J.S., Leone, M.A., Leppä, V., Liljedahl, U., Lima Bomfim, I., Lincoln, R.R., Link, J., Liu, J., Lorentzen, Å.R., Lupoli, S., Macciardi, F., Mack, T., Marriott, M., Martinelli, V., Mason, D., McCauley, J.L., Mentch, F., Mero, I-L, Mihalova, T., Montalban, X., Mottershead, J., Myhr, K-M, Naldi, P., Ollier, W., Page, A., Palotie, A., Pelletier, J., Piccio, L., Pickersgill, T., Piehl, F., Pobywajlo, S., Quach, H.L., Ramsay, P.P., Reunanen, M., Reynolds, R., Rioux, J.D., Rodegher, M., Roesner, S., Rubio, J.P., Rückert, I-M, Salvetti, M., Salvi, E., Santaniello, A., Schaefer, C.A., Schreiber, S., Schulze, C., Scott, R.J., Sellebjerg, F., Selmaj, K.W., Sexton, D., Shen, L., Simms-Acuna, B., Skidmore, S., Sleiman, P.M.A., Smestad, C., Sørensen, P.S., Søndergaard, H.B., Stankovich, J., Strange, R.C., Sulonen, A-M, Sundqvist, E., Syvänen, A-C, Taddeo, F., Taylor, B., Blackwell, J.M., Tienari, P., Bramon, E., Tourbah, A., Brown, M.A., Tronczynska, E., Casas, J.P., Tubridy, N., Corvin, A., Vickery, J., Jankowski, J., Villoslada, P., Markus, H.S., Wang, K., Mathew, C.G., Wason, J., Palmer, C.N.A., Wichmann, H-E, Plomin, R., Willoughby, E., Rautanen, A., Winkelmann, J., Wittig, M., Trembath, R.C., Yaouanq, J., Viswanathan, A.C., Zhang, H., Wood, N.W., Zuvich, R., Deloukas, P., Langford, C., Duncanson, A., Oksenberg, J.R., Pericak-Vance, M.A., Haines, J.L., Olsson, T., Hillert, J., Ivinson, A.J., De Jager, P.L., Peltonen, L., Stewart, G.J., Hafler, D.A., Hauser, S.L., McVean, G., Donnelly, P., Compston, A., Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C.C.A., Patsopoulos, N.A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S.E., Edkins, S., Gray, E., Booth, D.R., Potter, S.C., Goris, A., Band, G., Bang Oturai, A., Strange, A., Saarela, J., Bellenguez, C., Fontaine, B., Gillman, M., Hemmer, B., Gwilliam, R., Zipp, F., Jayakumar, A., Martin, R., Leslie, S., Hawkins, S., Giannoulatou, E., D’alfonso, S., Blackburn, H., Martinelli Boneschi, F., Liddle, J., Harbo, H.F., Perez, M.L., Spurkland, A., Waller, M.J., Mycko, M.P., Ricketts, M., Comabella, M., Hammond, N., Kockum, I., McCann, O.T., Ban, M., Whittaker, P., Kemppinen, A., Weston, P., Hawkins, C., Widaa, S., Zajicek, J., Dronov, S., Robertson, N., Bumpstead, S.J., Barcellos, L.F., Ravindrarajah, R., Abraham, R., Alfredsson, L., Ardlie, K., Aubin, C., Baker, A., Baker, K., Baranzini, S.E., Bergamaschi, L., Bergamaschi, R., Bernstein, A., Berthele, A., Boggild, M., Bradfield, J.P., Brassat, D., Broadley, S.A., Buck, D., Butzkueven, H., Capra, R., Carroll, W.M., Cavalla, P., Celius, E.G., Cepok, S., Chiavacci, R., Clerget-Darpoux, F., Clysters, K., Comi, G., Cossburn, M., Cournu-Rebeix, I., Cox, M.B., Cozen, W., Cree, B.A.C., Cross, A.H., Cusi, D., Daly, M.J., Davis, E., de Bakker, P.I.W., Debouverie, M., D’hooghe, M.B., Dixon, K., Dobosi, R., Dubois, B., Ellinghaus, D., Elovaara, I., Esposito, F., Fontenille, C., Foote, S., Franke, A., Galimberti, D., Ghezzi, A., Glessner, J., Gomez, R., Gout, O., Graham, C., Grant, S.F.A., Rosa Guerini, F., Hakonarson, H., Hall, P., Hamsten, A., Hartung, H-P, Heard, R.N., Heath, S., Hobart, J., Hoshi, M., Infante-Duarte, C., Ingram, G., Ingram, W., Islam, T., Jagodic, M., Kabesch, M., Kermode, A.G., Kilpatrick, T.J., Kim, C., Klopp, N., Koivisto, K., Larsson, M., Lathrop, M., Lechner-Scott, J.S., Leone, M.A., Leppä, V., Liljedahl, U., Lima Bomfim, I., Lincoln, R.R., Link, J., Liu, J., Lorentzen, Å.R., Lupoli, S., Macciardi, F., Mack, T., Marriott, M., Martinelli, V., Mason, D., McCauley, J.L., Mentch, F., Mero, I-L, Mihalova, T., Montalban, X., Mottershead, J., Myhr, K-M, Naldi, P., Ollier, W., Page, A., Palotie, A., Pelletier, J., Piccio, L., Pickersgill, T., Piehl, F., Pobywajlo, S., Quach, H.L., Ramsay, P.P., Reunanen, M., Reynolds, R., Rioux, J.D., Rodegher, M., Roesner, S., Rubio, J.P., Rückert, I-M, Salvetti, M., Salvi, E., Santaniello, A., Schaefer, C.A., Schreiber, S., Schulze, C., Scott, R.J., Sellebjerg, F., Selmaj, K.W., Sexton, D., Shen, L., Simms-Acuna, B., Skidmore, S., Sleiman, P.M.A., Smestad, C., Sørensen, P.S., Søndergaard, H.B., Stankovich, J., Strange, R.C., Sulonen, A-M, Sundqvist, E., Syvänen, A-C, Taddeo, F., Taylor, B., Blackwell, J.M., Tienari, P., Bramon, E., Tourbah, A., Brown, M.A., Tronczynska, E., Casas, J.P., Tubridy, N., Corvin, A., Vickery, J., Jankowski, J., Villoslada, P., Markus, H.S., Wang, K., Mathew, C.G., Wason, J., Palmer, C.N.A., Wichmann, H-E, Plomin, R., Willoughby, E., Rautanen, A., Winkelmann, J., Wittig, M., Trembath, R.C., Yaouanq, J., Viswanathan, A.C., Zhang, H., Wood, N.W., Zuvich, R., Deloukas, P., Langford, C., Duncanson, A., Oksenberg, J.R., Pericak-Vance, M.A., Haines, J.L., Olsson, T., Hillert, J., Ivinson, A.J., De Jager, P.L., Peltonen, L., Stewart, G.J., Hafler, D.A., Hauser, S.L., McVean, G., Donnelly, P., and Compston, A.

Abstract

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability1. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals2, 3, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk4. Modestly powered genome-wide association studies (GWAS)5, 6, 7, 8, 9, 10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility11. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Published
2011

34. Genetic variation at CR1increases risk of cerebral amyloid angiopathy

Author

Biffi, A., Shulman, J.M., Jagiella, J.M., Cortellini, L., Ayres, A.M., Schwab, K., Brown, D.L., Silliman, S.L., Selim, M., Worrall, B.B., Meschia, J.F., Slowik, A., De Jager, P.L., Greenberg, S.M., Schneider, J.A., Bennett, D.A., and Rosand, J.

Abstract

Accumulated evidence suggests that a variant within the CR1gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences -amyloid (A) deposition in brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular A deposition.

Published
2012
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35. HLA B44

Author

Healy, B.C., Liguori, M., Tran, D., Chitnis, T., Glanz, B., Wolfish, C., Gauthier, S., Buckle, G., Houtchens, M., Stazzone, L., Khoury, S., Hartzmann, R., Fernandez-Vina, M., Hafler, D.A., Weiner, H.L., Guttmann, C.R.G., and De Jager, P.L.

Abstract

In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB11501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B,and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A02, HLA B44, and HLA C05.

Published
2010
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36. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

Author

Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.

Subjects
Netherlands Twin Register (NTR), Male, Genome-wide association study, Logistic regression, Cohort Studies, Odds Ratio, pleiotropic genetic effects, Netherlands, Psychiatry, education.field_of_study, Likelihood Functions, Single Nucleotide, Middle Aged, Psychiatry and Mental health, educational attainment, depression, Major depressive disorder, Educational Status, Regression Analysis, Female, Psychology, Adult, Estonia, medicine.medical_specialty, Biochemistry & Molecular Biology, Aged, Depressive Disorder, Major/epidemiology, Depressive Disorder, Major/genetics, Depressive Disorder, Major/psychology, Estonia/epidemiology, Gene-Environment Interaction, Genetic Association Studies, Genotype, Humans, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Psychiatric Status Rating Scales, Concordance, Population, SNP, Single-nucleotide polymorphism, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, mental disorders, medicine, Polymorphism, education, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, major depressive disorder, ta1184, Neurosciences, Major, Odds ratio, medicine.disease, ta3124, Neurosciences & Neurology, polymorphisms, Demography
Abstract

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed

Published
2015

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