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51. Where does the Cetanic Break Take Place? Weakness of Will in Śāntideva’s Bodhicaryāvatāra

Author: Harris, S.E.
Published: 2016

52. BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis

Author: Wang, J., primary, Massoudi, D., additional, Ren, Y., additional, Muir, A.M., additional, Harris, S.E., additional, Greenspan, D.S., additional, and Feng, J.Q., additional
Published: 2017
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53. Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations

Author: Shah, S., Bonder, M.J., Marioni, R.E., Zhu, Z.H., McRae, A.F., Zhernakova, A., Harris, S.E., Liewald, D., Henders, A.K., Mendelson, M.M., Liu, C.Y., Joehanes, R., Liang, L.M., Levy, D., Martin, N.G., Starr, J.M., Wijmenga, C., Wray, N.R., Yang, J., Montgomery, G.W., Franke, L., Deary, I.J., Visscher, P.M., and BIOS Consortium
Published: 2015

54. 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., Lee, S.J. van der, Hellard, S. le, 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., Jager, P.L. de, Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., 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., Swieten, J.C. van, 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., Craen, A.J.M. de, Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L.G., Porteous, D.J., Raikkonen, 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., Duijn, C. van, Launer, L., Fitzpatrick, A.L., Seshadri, S., Jr, T.H.M., Deary, I.J., and Generation Scotland
Subjects: Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP], Social sciences: 200::Psychology: 260::Cognitive psychology: 267 [VDP], Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714 [VDP], Samfunnsvitenskap: 200::Psykologi: 260::Kognitiv psykologi: 267 [VDP]
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. publishedVersion
Published: 2015

55. Demandingness, Well-Being and the Bodhisattva Path

Author: Harris, S.E.
Published: 2015

56. On the Classification of Śāntideva’s Ethics in the Bodhicaryāvatāra

Author: Harris, S.E.
Published: 2015

57. Genome-wide association study identifies 74 loci associated with educational attainment

Author: Okbay, A., Beauchamp, J.P., Fontana, M.A., Lee, J.J., Pers, T.H., Rietveld, C.A., Turley, P., Chen, G.B., Emilsson, V., Meddens, S.F., Oskarsson, S., Pickrell, J.K., Thom, K., Timshel, P., Vlaming, R. de, Abdellaoui, A., Ahluwalia, T.S., Bacelis, J., Baumbach, C., Bjornsdottir, G., Brandsma, J.H., Pina Concas, M., Derringer, J., Furlotte, N.A., Galesloot, T.E., Girotto, G., Gupta, R, Hall, L.M., Harris, S.E., Hofer, E., Horikoshi, M., Huffman, J.E., Kaasik, K., Kalafati, I.P., Karlsson, R., Kong, A., Lahti, J., Lee, S.J. van der, deLeeuw, C., Lind, P.A., Lindgren, K.O., Liu, T., Mangino, M., Marten, J., Mihailov, E., Miller, M.B., Most, P.J. van der, Oldmeadow, C., Payton, A., Pervjakova, N., Peyrot, W.J., Qian, Y., Raitakari, O., Rueedi, R., Salvi, E., Schmidt, B., Schraut, K.E., Shi, J., Smith, A.V., Poot, R.A., Pourcain, B. St, Teumer, A., Thorleifsson, G., Verweij, N., Vuckovic, D., Wellmann, J., Westra, H.J., Yang, J., Zhao, W., Zhu, Z., Alizadeh, B.Z., Amin, N., Bakshi, A., Baumeister, S.E., Biino, G., Bonnelykke, K., Boyle, P.A., Campbell, H., Cappuccio, F.P., Davies, G., Neve, J.E. De, Deloukas, P., Demuth, I., Ding, J., Eibich, P., Eisele, L., Eklund, N., Evans, D.M., Faul, J.D., Feitosa, M.F., Forstner, A.J., Gandin, I., Gunnarsson, B., Halldorsson, B.V., Harris, T.B., Heath, A.C., Hocking, L.J., Holliday, E.G., Homuth, G., Horan, M.A., Franke, B., Kiemeney, L.A.L.M., et al., Okbay, A., Beauchamp, J.P., Fontana, M.A., Lee, J.J., Pers, T.H., Rietveld, C.A., Turley, P., Chen, G.B., Emilsson, V., Meddens, S.F., Oskarsson, S., Pickrell, J.K., Thom, K., Timshel, P., Vlaming, R. de, Abdellaoui, A., Ahluwalia, T.S., Bacelis, J., Baumbach, C., Bjornsdottir, G., Brandsma, J.H., Pina Concas, M., Derringer, J., Furlotte, N.A., Galesloot, T.E., Girotto, G., Gupta, R, Hall, L.M., Harris, S.E., Hofer, E., Horikoshi, M., Huffman, J.E., Kaasik, K., Kalafati, I.P., Karlsson, R., Kong, A., Lahti, J., Lee, S.J. van der, deLeeuw, C., Lind, P.A., Lindgren, K.O., Liu, T., Mangino, M., Marten, J., Mihailov, E., Miller, M.B., Most, P.J. van der, Oldmeadow, C., Payton, A., Pervjakova, N., Peyrot, W.J., Qian, Y., Raitakari, O., Rueedi, R., Salvi, E., Schmidt, B., Schraut, K.E., Shi, J., Smith, A.V., Poot, R.A., Pourcain, B. St, Teumer, A., Thorleifsson, G., Verweij, N., Vuckovic, D., Wellmann, J., Westra, H.J., Yang, J., Zhao, W., Zhu, Z., Alizadeh, B.Z., Amin, N., Bakshi, A., Baumeister, S.E., Biino, G., Bonnelykke, K., Boyle, P.A., Campbell, H., Cappuccio, F.P., Davies, G., Neve, J.E. De, Deloukas, P., Demuth, I., Ding, J., Eibich, P., Eisele, L., Eklund, N., Evans, D.M., Faul, J.D., Feitosa, M.F., Forstner, A.J., Gandin, I., Gunnarsson, B., Halldorsson, B.V., Harris, T.B., Heath, A.C., Hocking, L.J., Holliday, E.G., Homuth, G., Horan, M.A., Franke, B., Kiemeney, L.A.L.M., and et al.
Abstract: Contains fulltext : 167137.pdf (publisher's version ) (Closed access), Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016

58. Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions

Author: Hill, W.D. (W. David), Davies, G. (Gail), Harris, S.E. (Sarah), Hagenaars, S. (Saskia), Liewald, D.C.M. (David), Penke, L., Gale, C.R., Deary, I.J., Deary, I.J. (Ian), Debette, S. (Stéphanie), Verbaas, C.I. (Carla I.), Bressler, J. (Jan), Schuur, M. (Maaike), Smith, A.V. (Albert Vernon), Bis, J.C. (Joshua), Bennett, D.A. (David), Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, Mosley, T.H. (Thomas H.), Hill, W.D. (W. David), Davies, G. (Gail), Harris, S.E. (Sarah), Hagenaars, S. (Saskia), Liewald, D.C.M. (David), Penke, L., Gale, C.R., Deary, I.J., Deary, I.J. (Ian), Debette, S. (Stéphanie), Verbaas, C.I. (Carla I.), Bressler, J. (Jan), Schuur, M. (Maaike), Smith, A.V. (Albert Vernon), Bis, J.C. (Joshua), Bennett, D.A. (David), Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, and Mosley, T.H. (Thomas H.)
Abstract: Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n =53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissuespecific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ∼2.6% of the SNPs from each GWAS but accounted for ∼ 40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.
Published: 2016
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59. Personality polygenes, positive affect, and life satisfaction

Author: Weiss, A. (Alexander), Baselmans, B.M.L. (Bart M. L.), Hofer, E. (Edith), Yang, J. (Jingyun), Okbay, A. (Aysu), Lind, P.A. (Penelope), Miller, M. (Mike), Nolte, I.M. (Ilja), Zhao, W. (Wei), Hagenaars, S. (Saskia), Hottenga, J.J. (Jouke Jan), Matteson, L.K. (Lindsay K.), Snieder, H. (Harold), Faul, J.D. (Jessica D.), Hartman, C.A. (C.), Boyle, P.A. (Patricia A.), Tiemeier, H.W. (Henning), Mosing, M. (Miriam), Pattie, A. (Alison), Davies, G. (Gail), Liewald, D.C.M. (David), Schmidt, R. (Reinhold), Jager, P.L. (Philip) de, Heath, A.C. (Andrew C.), Jokela, M. (Markus), Starr, J.M. (John), Oldehinkel, A.J. (Albertine), Johannesson, M. (Magnus), Cesarini, D. (David), Hofman, A. (Albert), Harris, S.E. (Sarah), Smith, J.A. (Jennifer A), Keltikangas-JÃ¤rvinen, L. (Liisa), Pulkki-RÃ¥back, L. (Laura), Smith, J. (Jacqui), Iacono, W.G. (William), McGue, M. (Matt), Bennett, D.A. (David A.), Pedersen, N.L. (Nancy), Magnusson, P.K. (Patrik), Deary, I.J. (Ian), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Bartels, M. (Meike), Luciano, M. (Michelle), Weiss, A. (Alexander), Baselmans, B.M.L. (Bart M. L.), Hofer, E. (Edith), Yang, J. (Jingyun), Okbay, A. (Aysu), Lind, P.A. (Penelope), Miller, M. (Mike), Nolte, I.M. (Ilja), Zhao, W. (Wei), Hagenaars, S. (Saskia), Hottenga, J.J. (Jouke Jan), Matteson, L.K. (Lindsay K.), Snieder, H. (Harold), Faul, J.D. (Jessica D.), Hartman, C.A. (C.), Boyle, P.A. (Patricia A.), Tiemeier, H.W. (Henning), Mosing, M. (Miriam), Pattie, A. (Alison), Davies, G. (Gail), Liewald, D.C.M. (David), Schmidt, R. (Reinhold), Jager, P.L. (Philip) de, Heath, A.C. (Andrew C.), Jokela, M. (Markus), Starr, J.M. (John), Oldehinkel, A.J. (Albertine), Johannesson, M. (Magnus), Cesarini, D. (David), Hofman, A. (Albert), Harris, S.E. (Sarah), Smith, J.A. (Jennifer A), Keltikangas-JÃ¤rvinen, L. (Liisa), Pulkki-RÃ¥back, L. (Laura), Smith, J. (Jacqui), Iacono, W.G. (William), McGue, M. (Matt), Bennett, D.A. (David A.), Pedersen, N.L. (Nancy), Magnusson, P.K. (Patrik), Deary, I.J. (Ian), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Bartels, M. (Meike), and Luciano, M. (Michelle)
Abstract: Copyright Â
Published: 2016
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60. Genome-wide association study identifies 74 loci associated with educational attainment

Author: Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Benjamin, D.J. (Daniel J.), Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), and Benjamin, D.J. (Daniel J.)
Abstract: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016
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61. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author: Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), Munroe, P. (Patricia), Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), and Munroe, P. (Patricia)
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Published: 2016
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62. Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank

Author: Hill, W.D. (W. David), Hagenaars, S. (Saskia), Marioni, R.E. (Riccardo), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Davies, G. (Gail), Okbay, A. (Aysu), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Deary, I.J. (Ian), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Marioni, R.E. (Riccardo), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Davies, G. (Gail), Okbay, A. (Aysu), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), and Deary, I.J. (Ian)
Abstract: Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses and tend to die at an earlier age [1–3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [4]. However, common SNPs have been found collectively to explain around 18% of the phenotypic variance of an area-based social deprivation measure of SES [5]. Molecular genetic studies have also shown that common physical and psychiatric diseases are partly heritable [6]. It is possible that phenotypic associations between SES and health arise partly due to a shared genetic etiology. We conducted a genome-wide association study (GWAS) on social deprivation and on household income using 112,151 participants of UK Biobank. We find that common SNPs explain 21% of the variation in social deprivation and 11% of household income. Two independent loci attained genome-wide significance for household income, with the most significant SNP in each of these loci being rs187848990 on chromosome 2 and rs8100891 on chromosome 19. Genes in the regions of these SNPs have been associated with intellectual disabilities, schizophrenia, and synaptic plasticity. Extensive genetic correlations were found between both measures of SES and illnesses, anthropometric variables, psychiatric disorders, and cognitive ability. These findings suggest that some SNPs associated with SES are involved in the brain and central nervous system. The genetic associations with SES obviously do not reflect direct causal effects and are probably mediated via other partly heritable variables, including cognitive ability, personality, and health.
Published: 2016
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63. Independent De Novo 22q11.2 Deletions in Two First Cousins with Velocardiofacial Syndrome

Author: Saitta, S.C., Harris, S.E., Driscoll, D.A., Emanuel, B.S., McDonald-McGinn, D., and Zackai, E.H.
Subjects: Human genetics -- Research, Immunological deficiency syndromes -- Genetic aspects, Chromosomes -- Physiological aspects, Biological sciences
Published: 2001

64. Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

Author: Lyall, D.M., Harris, S.E., Bastin, M.E., Muñoz Maniega, S., Murray, C., Lutz, M.W., Saunders, A.M., Roses, A.D., Valdés Hernández, M. del C., Royle, N.A., Starr, J.M., Porteous, D.J., Wardlaw, J.M., and Deary, I.J.
Subjects: ALZHEIMERS-DISEASE, AGE, ONSET, MEMORY, INFANTS, TRACTOGRAPHY, PERFORMANCE, BIRTH COHORT 1936, POLYMORPHISM
Abstract: Genetic polymorphisms in the APOE ε and TOMM40 ‘523’ poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer’s disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ε2/ε3/ε4 status and TOMM40 523 poly-T repeat length. Data were available from 758–814 subjects for cognitive analysis, and 522–543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all
Published: 2014

65. VISUAL AND ACOUSTIC SIGNALLING IN THE MUSICAL FIDDLER CRAB (UCA MUSICA) FROM WESTERN MEXICO

Author: Harris, S.E., Woodward, D.M., Fontaine, J.L., and Barnwell, F.H.
Subjects: Zoological research -- Analysis, Sound production by animals -- Analysis, Fiddler-crabs -- Psychological aspects
Abstract: Uca musica males possess a stridulatory apparatus consisting of ridges on the underside of the major cheliped and an opposable row of tubercles on the face of the first walking leg. We recorded sounds from a crab under lab conditions and filmed and videotaped waving displays of males at San Bias and Manzanillo. Means for individual sounds (N=20) during a sustained series were: duration, 0.79 s; number of pulses per sound, 25; pulse repetition rate, 31.6 per s. Pulses were sharply defined at the beginning of a sound but became more complex as, presumably, the stridulatory surfaces of the cheliped and walking leg were engaged. Waving displays resembled those in U. terpsichores, switching from a low intensity lateral circular motion of the large claw (averaging 1.6 s from start to finish) to a high intensity series of rapid (2.6 per s) downward thrusts of the forward-directed chelipeds when females approached the burrow entrance of the male.
Published: 1998

66. Modulation of genetic associations with serum urate levels by body-mass-index in humans

Author: Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), Vitart, V. (Veronique), Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), and Vitart, V. (Veronique)
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 × 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 × 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight = 9.1 × 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P difflean-obese= 2 × 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obsogenic environment.
Published: 2015
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67. Directional dominance on stature and cognition in diverse human populations.

Author: BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., and Wilson, J.F.
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolu
Published: 2015

68. Recurrent Coding Sequence Variation Explains only A Small Fraction of the Genetic Architecture of Colorectal Cancer

Author: Timofeeva, M.N. (Maria N.), Kinnersley, B. (Ben), Farrington, S.M. (Susan M.), Whiffin, N. (Nicola), Palles, C. (Claire), Svinti, V. (Victoria), Lloyd, A. (Amy), Gorman, M. (Maggie), Ooi, L.-Y. (Li-Yin), Hosking, F. (Fay), Barclay, E. (Ella), Zgaga, L. (Lina), Dobbins, S.E. (Sara E.), Martin, L. (Lynn), Theodoratou, E. (Evropi), Broderick, P. (Peter), Tenesa, A. (Albert), Smillie, C. (Claire), Grimes, G. (Graeme), Hayward, C. (Caroline), Campbell, A. (Archie), Porteous, D. (David), Deary, I.J. (Ian), Harris, S.E. (Sarah), Northwood, J.B. (John Blackman), Barrett, J.H. (Jennifer H.), Smith, G. (Gillian), Wolf, R. (Roland), Forman, D. (David), Morreau, H. (Hans), Ruano, D. (Dina), Tops, C. (Carli), Wijnen, J.T. (Juul), Schrumpf, M. (Melanie), Boot, A. (Arnoud), Vasen, H. (Hans), Hes, F.J. (Frederik), Wezel, T. (Tom) van, Franke, A. (Andre), Lieb, W. (Wolgang), Schafmayer, C. (Clemens), Hampe, J. (Jochen), Buch, T. (Thorsten), Propping, P. (Peter), Hemminki, K. (Kari), Försti, A. (Asta), Westers, H. (Helga), Hofstra, R.M.W. (Robert), Pinheiro, M. (Manuela), Pinto, C. (Carla), Teixeira, P.J., Ruiz-Ponte, C. (Clara), Fernández-Rozadilla, C. (Ceres), Carracedo, A. (Angel), Castells, A., Castellví-Bel, S., Campbell, H. (Harry), Bishop, D.T. (David Timothy), Tomlinson, I. (Ian), Dunlop, M.G. (Malcolm), Houlston, R. (Richard), Timofeeva, M.N. (Maria N.), Kinnersley, B. (Ben), Farrington, S.M. (Susan M.), Whiffin, N. (Nicola), Palles, C. (Claire), Svinti, V. (Victoria), Lloyd, A. (Amy), Gorman, M. (Maggie), Ooi, L.-Y. (Li-Yin), Hosking, F. (Fay), Barclay, E. (Ella), Zgaga, L. (Lina), Dobbins, S.E. (Sara E.), Martin, L. (Lynn), Theodoratou, E. (Evropi), Broderick, P. (Peter), Tenesa, A. (Albert), Smillie, C. (Claire), Grimes, G. (Graeme), Hayward, C. (Caroline), Campbell, A. (Archie), Porteous, D. (David), Deary, I.J. (Ian), Harris, S.E. (Sarah), Northwood, J.B. (John Blackman), Barrett, J.H. (Jennifer H.), Smith, G. (Gillian), Wolf, R. (Roland), Forman, D. (David), Morreau, H. (Hans), Ruano, D. (Dina), Tops, C. (Carli), Wijnen, J.T. (Juul), Schrumpf, M. (Melanie), Boot, A. (Arnoud), Vasen, H. (Hans), Hes, F.J. (Frederik), Wezel, T. (Tom) van, Franke, A. (Andre), Lieb, W. (Wolgang), Schafmayer, C. (Clemens), Hampe, J. (Jochen), Buch, T. (Thorsten), Propping, P. (Peter), Hemminki, K. (Kari), Försti, A. (Asta), Westers, H. (Helga), Hofstra, R.M.W. (Robert), Pinheiro, M. (Manuela), Pinto, C. (Carla), Teixeira, P.J., Ruiz-Ponte, C. (Clara), Fernández-Rozadilla, C. (Ceres), Carracedo, A. (Angel), Castells, A., Castellví-Bel, S., Campbell, H. (Harry), Bishop, D.T. (David Timothy), Tomlinson, I. (Ian), Dunlop, M.G. (Malcolm), and Houlston, R. (Richard)
Abstract: Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10-7), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10-7); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10-7
Published: 2015
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69. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

Author: Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), Smith, N.L. (Nicholas), Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), and Smith, N.L. (Nicholas)
Abstract: Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified
Published: 2015
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70. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Author: Kato, N. (Norihiro), Loh, M. (Marie), Takeuchi, F. (Fumihiko), Verweij, N. (Niek), Wang, X. (Xu), Zhang, W. (Weihua), NKelly, T. (Tanika), Saleheen, D., Lehne, B. (Benjamin), Leach, I.M. (Irene Mateo), Drong, A. (Alexander), Abbott, J. (James), Wahl, S. (Simone), Tan, S.-T. (Sian-Tsung), Scott, W.R. (William R.), Campanella, G. (Gianluca), Chadeau-Hyam, M. (Marc), Afzal, U. (Uzma), Ahluwalia, T.S. (Tarunveer Singh), Bonder, M.J. (Marc), Chen, P. (Ping), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Esko, T. (Tõnu), Go, M.J. (Min Jin), Harris, S.E. (Sarah), Hartiala, J. (Jaana), Kasela, S. (Silva), Kasturiratne, A. (Anuradhani), Khor, C.C., Kleber, M.E. (Marcus), Li, H. (Huaixing), Mok, Z.Y. (Zuan Yu), Nakatochi, M. (Masahiro), Sapari, N.S. (Nur Sabrina), Saxena, R. (Richa), Stewart, A.F. (Alexandre F.), Stolk, L. (Lisette), Tabara, Y. (Yasuharu), Teh, A.L. (Ai Ling), Wu, Y. (Ying), Wu, J.-Y. (Jer-Yuarn), Zhang, Y. (Yi), Aits, I. (Imke), Da Silva Couto Alves, A. (Alexessander), Das, S. (Shikta), Dorajoo, R. (Rajkumar), CHopewell, J. (Jemma), Kim, Y.K. (Yun Kyoung), WKoivula, R. (Robert), Luan, J. (Jian'An), Lyytikäinen, L.-P. (Leo-Pekka), NNguyen, Q. (Quang), Pereira, M.A. (Mark A), Postmus, D. (Douwe), TRaitakari, O. (Olli), Scannell Bryan, M. (Molly), Scott, R.A. (Robert), Sorice, R., Tragante, V. (Vinicius), Traglia, M. (Michela), White, J. (Jon), Yamamoto, K. (Ken), Zhang, Y. (Yonghong), Adair, L.S. (Linda), Ahmed, A. (Alauddin), Akiyama, K. (Koichi), Asif, R. (Rasheed), Aung, T. (Tin), Barroso, I.E. (Inês), Bjonnes, A. (Andrew), Braun, T.R. (Timothy R.), Cai, H. (Hui), Chang, L.-C. (Li-Ching), Chen, C.-H., Cheng, C-Y. (Ching-Yu), Chong, Y.-S. (Yap-Seng), Collins, F.S. (Francis), Courtney, R. (Regina), Davies, G. (Gail), Delgado, G., Do, L.D. (Loi D.), Doevendans, P.A. (Pieter), Gansevoort, R.T. (Ron), Gao, Y. (Ying), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grewal, J. (Jagvir), Gu, D. (D.), SWander, G. (Gurpreet), Hartikainen, A.L., Hazen, S.L. (Stanley), He, J. (Jing), Heng, C.K. (Chew-Kiat), Hixso, E.J.A. (E. James Ames), Hofman, A. (Albert), Hsu, C. (Chris), Huang, W. (Wei), Husemoen, L.L.N. (Lise Lotte), Hwang, J.-Y. (Joo-Yeon), Ichihara, S. (Sahoko), Igase, M. (Michiya), Isono, M. (Masato), Justesen, J.M. (Johanne M.), Katsuya, T. (Tomohiro), GKibriya, M. (Muhammad), Kim, Y.J., Kishimoto, M. (Miyako), Koh, W.-P. (Woon-Puay), Kohara, K. (Katsuhiko), Kumari, M. (Meena), Kwek, K. (Kenneth), Lee, N.R. (Nanette), Lee, J. (Jeannette), Liao, J. (Jie), Lieb, W. (Wolfgang), Liewald, D.C.M. (David), Matsubara, T. (Tatsuaki), Matsushita, Y. (Yumi), Meitinger, T. (Thomas), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Mononen, K. (Kari), Müller-Nurasyid, M. (Martina), Nabika, T. (Toru), Nakashima, E. (Eitaro), Ng, H.K. (Hong Kiat), Nikus, K. (Kjell), Nutile, T., Ohkubo, T. (Takayoshi), Ohnaka, K. (Keizo), Parish, S. (Sarah), Paternoster, L. (Lavinia), Peng, H. (Hao), Peters, A. (Annette), TPham, S. (Son), Pinidiyapathirage, M.J. (Mohitha J.), Rahman, M. (Mahfuzar), Rakugi, H. (Hiromi), Rolandsson, O. (Olov), Rozario, M.A. (Michelle Ann), Ruggiero, D., Sala, C. (Cinzia), Sarju, R. (Ralhan), Shimokawa, K. (Kazuro), Snieder, H. (Harold), Sparsø, T. (Thomas), Spiering, W. (Wilko), Starr, J.M. (John), Stott, D.J. (David J.), OStram, D. (Daniel), Sugiyama, T. (Takao), Szymczak, S. (Silke), Tang, W.H.W. (W.H. Wilson), Tong, L. (Lin), Trompet, S. (Stella), Turjanmaa, V. (Väinö), Ueshima, H. (Hirotsugu), Uitterlinden, A.G. (André), Umemura, S. (Satoshi), Vaarasmaki, M. (Marja), Dam, R.M. (Rob Mvan), Gilst, W.H. (Wiek) van, Veldhuisen, D.J. (Dirk) van, Viikari, J. (Jorma), Waldenberger, M. (Melanie), Wang, Y. (Yiqin), Wang, A. (Aili), Wilson, R. (Rory), Wong, T.Y. (Tien Yin), Xiang, Y.-B. (Yong-Bing), Yamaguchi, S. (Shuhei), Ye, X. (Xingwang), Young, R. (Robin), Young, T.L. (Terri), Yuan, J.-M. (Jian-Min), Zhou, X. (Xueya), Asselbergs, F.W. (Folkert), Ciullo, M., Clarke, R. (Robert), Deloukas, P. (Panagiotis), Franke, A. (Andre), Paul, W.F. (W. Frank), Franks, S. (Steve), Friedlander, Y. (Yechiel), Gross, M.D. (Myron D.), Guo, Z. (Zhirong), Hansen, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Jørgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kajio, H. (Hiroshi), Kivimaki, M. (Mika), Lee, J.-Y. (Jong-Young), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Miki, T. (Tetsuro), Pedersen, O. (Oluf), Samani, N.J. (Nilesh), Sørensen, T.I.A. (Thorkild), Takayanagi, R. (Ryoichi), Toniolo, D. (Daniela), Ahsan, H. (Habibul), Allayee, H. (Hooman), Chen, Y.-T. (Yuan-Tsong), Danesh, J. (John), Deary, I.J. (Ian), Franco, O.H. (Oscar), Franke, L. (Lude), THeijman, B. (Bastiaan), Holbrook, J.D. (Joanna D.), Isaacs, A.J. (Aaron), Kim, B.-J. (Bong-Jo), Lin, X. (Xu), Liu, J. (Jianjun), März, W. (Winfried), Metspalu, A. (Andres), Mohlke, K.L. (Karen), Sangher, K., Harambir, D. (Dharambir), Shu, X.-O. (Xiao-Ou), Meurs, J.B.J. (Joyce) van, Vithana, E.N. (Eranga), Wickremasinghe, A.R. (Ananda), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.W. (Bruce H.W.), Yokota, M. (Mitsuhiro), Zheng, W. (Wei), Zhu, D. (Dingliang), Vineis, P. (Paolo), Kyrtopoulos, S.A. (Soterios A.), Kleinjans, J.C.S. (Jos C.S.), McCarthy, M.I. (Mark), Soong, R. (Richie), Gieger, C. (Christian), Scott, J. (James), Teo, Y.Y. (Yik Ying), He, J. (Jiang), Elliott, P. (Paul), Tai, E.S. (Shyong), Harst, P. (Pim) van der, Kooner, J.S. (Jaspal S.), Chambers, J.C. (John), Kato, N. (Norihiro), Loh, M. (Marie), Takeuchi, F. (Fumihiko), Verweij, N. (Niek), Wang, X. (Xu), Zhang, W. (Weihua), NKelly, T. (Tanika), Saleheen, D., Lehne, B. (Benjamin), Leach, I.M. (Irene Mateo), Drong, A. (Alexander), Abbott, J. (James), Wahl, S. (Simone), Tan, S.-T. (Sian-Tsung), Scott, W.R. (William R.), Campanella, G. (Gianluca), Chadeau-Hyam, M. (Marc), Afzal, U. (Uzma), Ahluwalia, T.S. (Tarunveer Singh), Bonder, M.J. (Marc), Chen, P. (Ping), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Esko, T. (Tõnu), Go, M.J. (Min Jin), Harris, S.E. (Sarah), Hartiala, J. (Jaana), Kasela, S. (Silva), Kasturiratne, A. (Anuradhani), Khor, C.C., Kleber, M.E. (Marcus), Li, H. (Huaixing), Mok, Z.Y. (Zuan Yu), Nakatochi, M. (Masahiro), Sapari, N.S. (Nur Sabrina), Saxena, R. (Richa), Stewart, A.F. (Alexandre F.), Stolk, L. (Lisette), Tabara, Y. (Yasuharu), Teh, A.L. (Ai Ling), Wu, Y. (Ying), Wu, J.-Y. (Jer-Yuarn), Zhang, Y. (Yi), Aits, I. (Imke), Da Silva Couto Alves, A. (Alexessander), Das, S. (Shikta), Dorajoo, R. (Rajkumar), CHopewell, J. (Jemma), Kim, Y.K. (Yun Kyoung), WKoivula, R. (Robert), Luan, J. (Jian'An), Lyytikäinen, L.-P. (Leo-Pekka), NNguyen, Q. (Quang), Pereira, M.A. (Mark A), Postmus, D. (Douwe), TRaitakari, O. (Olli), Scannell Bryan, M. (Molly), Scott, R.A. (Robert), Sorice, R., Tragante, V. (Vinicius), Traglia, M. (Michela), White, J. (Jon), Yamamoto, K. (Ken), Zhang, Y. (Yonghong), Adair, L.S. (Linda), Ahmed, A. (Alauddin), Akiyama, K. (Koichi), Asif, R. (Rasheed), Aung, T. (Tin), Barroso, I.E. (Inês), Bjonnes, A. (Andrew), Braun, T.R. (Timothy R.), Cai, H. (Hui), Chang, L.-C. (Li-Ching), Chen, C.-H., Cheng, C-Y. (Ching-Yu), Chong, Y.-S. (Yap-Seng), Collins, F.S. (Francis), Courtney, R. (Regina), Davies, G. (Gail), Delgado, G., Do, L.D. (Loi D.), Doevendans, P.A. (Pieter), Gansevoort, R.T. (Ron), Gao, Y. (Ying), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grewal, J. (Jagvir), Gu, D. (D.), SWander, G. (Gurpreet), Hartikainen, A.L., Hazen, S.L. (Stanley), He, J. (Jing), Heng, C.K. (Chew-Kiat), Hixso, E.J.A. (E. James Ames), Hofman, A. (Albert), Hsu, C. (Chris), Huang, W. (Wei), Husemoen, L.L.N. (Lise Lotte), Hwang, J.-Y. (Joo-Yeon), Ichihara, S. (Sahoko), Igase, M. (Michiya), Isono, M. (Masato), Justesen, J.M. (Johanne M.), Katsuya, T. (Tomohiro), GKibriya, M. (Muhammad), Kim, Y.J., Kishimoto, M. (Miyako), Koh, W.-P. (Woon-Puay), Kohara, K. (Katsuhiko), Kumari, M. (Meena), Kwek, K. (Kenneth), Lee, N.R. (Nanette), Lee, J. (Jeannette), Liao, J. (Jie), Lieb, W. (Wolfgang), Liewald, D.C.M. (David), Matsubara, T. (Tatsuaki), Matsushita, Y. (Yumi), Meitinger, T. (Thomas), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Mononen, K. (Kari), Müller-Nurasyid, M. (Martina), Nabika, T. (Toru), Nakashima, E. (Eitaro), Ng, H.K. (Hong Kiat), Nikus, K. (Kjell), Nutile, T., Ohkubo, T. (Takayoshi), Ohnaka, K. (Keizo), Parish, S. (Sarah), Paternoster, L. (Lavinia), Peng, H. (Hao), Peters, A. (Annette), TPham, S. (Son), Pinidiyapathirage, M.J. (Mohitha J.), Rahman, M. (Mahfuzar), Rakugi, H. (Hiromi), Rolandsson, O. (Olov), Rozario, M.A. (Michelle Ann), Ruggiero, D., Sala, C. (Cinzia), Sarju, R. (Ralhan), Shimokawa, K. (Kazuro), Snieder, H. (Harold), Sparsø, T. (Thomas), Spiering, W. (Wilko), Starr, J.M. (John), Stott, D.J. (David J.), OStram, D. (Daniel), Sugiyama, T. (Takao), Szymczak, S. (Silke), Tang, W.H.W. (W.H. Wilson), Tong, L. (Lin), Trompet, S. (Stella), Turjanmaa, V. (Väinö), Ueshima, H. (Hirotsugu), Uitterlinden, A.G. (André), Umemura, S. (Satoshi), Vaarasmaki, M. (Marja), Dam, R.M. (Rob Mvan), Gilst, W.H. (Wiek) van, Veldhuisen, D.J. (Dirk) van, Viikari, J. (Jorma), Waldenberger, M. (Melanie), Wang, Y. (Yiqin), Wang, A. (Aili), Wilson, R. (Rory), Wong, T.Y. (Tien Yin), Xiang, Y.-B. (Yong-Bing), Yamaguchi, S. (Shuhei), Ye, X. (Xingwang), Young, R. (Robin), Young, T.L. (Terri), Yuan, J.-M. (Jian-Min), Zhou, X. (Xueya), Asselbergs, F.W. (Folkert), Ciullo, M., Clarke, R. (Robert), Deloukas, P. (Panagiotis), Franke, A. (Andre), Paul, W.F. (W. Frank), Franks, S. (Steve), Friedlander, Y. (Yechiel), Gross, M.D. (Myron D.), Guo, Z. (Zhirong), Hansen, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Jørgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kajio, H. (Hiroshi), Kivimaki, M. (Mika), Lee, J.-Y. (Jong-Young), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Miki, T. (Tetsuro), Pedersen, O. (Oluf), Samani, N.J. (Nilesh), Sørensen, T.I.A. (Thorkild), Takayanagi, R. (Ryoichi), Toniolo, D. (Daniela), Ahsan, H. (Habibul), Allayee, H. (Hooman), Chen, Y.-T. (Yuan-Tsong), Danesh, J. (John), Deary, I.J. (Ian), Franco, O.H. (Oscar), Franke, L. (Lude), THeijman, B. (Bastiaan), Holbrook, J.D. (Joanna D.), Isaacs, A.J. (Aaron), Kim, B.-J. (Bong-Jo), Lin, X. (Xu), Liu, J. (Jianjun), März, W. (Winfried), Metspalu, A. (Andres), Mohlke, K.L. (Karen), Sangher, K., Harambir, D. (Dharambir), Shu, X.-O. (Xiao-Ou), Meurs, J.B.J. (Joyce) van, Vithana, E.N. (Eranga), Wickremasinghe, A.R. (Ananda), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.W. (Bruce H.W.), Yokota, M. (Mitsuhiro), Zheng, W. (Wei), Zhu, D. (Dingliang), Vineis, P. (Paolo), Kyrtopoulos, S.A. (Soterios A.), Kleinjans, J.C.S. (Jos C.S.), McCarthy, M.I. (Mark), Soong, R. (Richie), Gieger, C. (Christian), Scott, J. (James), Teo, Y.Y. (Yik Ying), He, J. (Jiang), Elliott, P. (Paul), Tai, E.S. (Shyong), Harst, P. (Pim) van der, Kooner, J.S. (Jaspal S.), and Chambers, J.C. (John)
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5.0 × 10 -21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10 -6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
Published: 2015
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71. 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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72. Genes from a translational analysis support a multifactorial nature of white matter hyperintensities

Author: Lopez, L.M. (Lorna), Hill, W.D. (W. David), Harris, S.E. (Sarah), Valdés Hernández, M.C. (Maria), Muñoz Maniega, S. (Susana), Bastin, M.E. (Mark), Bailey, E. (Emma), Smith, C. (Colin), McBride, M. (Martin), McClure, J. (John), Graham, D. (Delyth), Dominiczak, A. (Anna), Yang, Q. (Qiong Fang), Fornage, M. (Myriam), Ikram, M.A. (Arfan), Debette, S. (Stéphanie), Launer, L.J. (Lenore), Bis, J.C. (Joshua), Schmidt, R. (Reinhold), Seshadri, S. (Sudha), Porteous, D.J. (David J.), Starr, J.M. (John), Deary, I.J. (Ian), Wardlaw, J.M. (J.), Lopez, L.M. (Lorna), Hill, W.D. (W. David), Harris, S.E. (Sarah), Valdés Hernández, M.C. (Maria), Muñoz Maniega, S. (Susana), Bastin, M.E. (Mark), Bailey, E. (Emma), Smith, C. (Colin), McBride, M. (Martin), McClure, J. (John), Graham, D. (Delyth), Dominiczak, A. (Anna), Yang, Q. (Qiong Fang), Fornage, M. (Myriam), Ikram, M.A. (Arfan), Debette, S. (Stéphanie), Launer, L.J. (Lenore), Bis, J.C. (Joshua), Schmidt, R. (Reinhold), Seshadri, S. (Sudha), Porteous, D.J. (David J.), Starr, J.M. (John), Deary, I.J. (Ian), and Wardlaw, J.M. (J.)
Abstract: BACKGROUND AND PURPOSE - : White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS - : We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. RESULTS - : Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10; FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM6
Published: 2015
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73. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), Wilson, J.F. (James), Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), and Wilson, J.F. (James)
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been p
Published: 2015
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74. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Author: Sabater-Lleal, M., Huang, J., Chasman, D., Naitza, S., Dehghan, A., Johnson, A.D., Teumer, A., Reiner, A.P., Folkersen, L., Basu, S., Rudnicka, A.R., Trompet, S., Malarstig, A., Baumert, J., Bis, J.C., Guo, X.Q., Hottenga, J.J., Shin, S.Y., Lopez, L.M., Lahti, J., Tanaka, T., Yanek, L.R., Oudot-Mellakh, T., Wilson, J.F., Navarro, P., Huffman, J.E., Zemunik, T., Redline, S., Mehra, R., Pulanic, D., Rudan, I., Wright, A.F., Kolcic, I., Polasek, O., Wild, S.H., Campbell, H., Curb, J.D., Wallace, R., Liu, S.M., Eaton, C.B., Becker, D.M., Becker, L.C., Bandinelli, S., Raikkonen, K., Widen, E., Palotie, A., Fornage, M., Green, D., Gross, M., Davies, G., Harris, S.E., Liewald, D.C., Starr, J.M., Williams, F.M.K., Grant, P.J., Spector, T.D., Strawbridge, R.J., Silveira, A., Sennblad, B., Rivadeneira, F., Uitterlinden, A.G., Franco, O.H., Hofman, A., Dongen, J. van, Willemsen, G., Boomsma, D.I., Yao, J., Jenny, N.S., Haritunians, T., McKnight, B., Lumley, T., Taylor, K.D., Rotter, J.I., Psaty, B.M., Peters, A., Gieger, C., Illig, T., Grotevendt, A., Homuth, G., Volzke, H., Kocher, T., Goel, A., Franzosi, M.G., Seedorf, U., Clarke, R., Steri, M., Tarasov, K.V., Sanna, S., Schlessinger, D., Stott, D.J., Sattar, N., Buckley, B.M., Rumley, A., Lowe, G.D., McArdle, W.L., Chen, M.H., Tofler, G.H., Song, J., Boerwinkle, E., Folsom, A.R., Rose, L.M., Franco-Cereceda, A., Teichert, M., Ikram, M.A., Mosley, T.H., Bevan, S., Dichgans, M., Rothwell, P.M., Sudlow, C.L.M., Hopewell, J.C., Chambers, J.C., Saleheen, D., Kooner, J.S., Danesh, J., Nelson, C.P., Erdmann, J., Reilly, M.P., Kathiresan, S., Schunkert, H., Morange, P.E., Ferrucci, L., Eriksson, J.G., Jacobs, D., Deary, I.J., Soranzo, N., Witteman, J.C.M., Geus, E.J.C. de, Tracy, R.P., Hayward, C., Koenig, W., Cucca, F., Jukema, J.W., Eriksson, P., Seshadri, S., Markus, H.S., Watkins, H., Samani, N.J., Wallaschofski, H., Smith, N.L., Tregouet, D., Ridker, P.M., Tang, W.H., Strachan, D.P., Hamsten, A., O'Donnell, C.J., VTE Consortium, STROKE Consortium, WTCCC2, CD4 Consortium, CARDIoGRAM Consortium, Epidemiology, Cell biology, Urology, Internal Medicine, Immunology, Radiology & Nuclear Medicine, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Male, Netherlands Twin Register (NTR), Pathology, Myocardial Infarction, Genome-wide association study, Coronary Artery Disease, Disease, VARIANTS, 030204 cardiovascular system & hematology, Fibrinogen, Genome, 0302 clinical medicine, Risk Factors, Genotype, ARTERY-DISEASE, GENE-EXPRESSION, Aged, 80 and over, Genetics, INDIVIDUAL PARTICIPANT METAANALYSIS, 0303 health sciences, Hispanic or Latino, Venous Thromboembolism, Middle Aged, 3. Good health, Stroke, Meta-analysis, Medical genetics, Female, HEALTH, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, medicine.medical_specialty, cardiovascular diseases, fibrinogen, gene expression, genome-wide association study, Adolescent, Implementation Science [NCEBP 3], Black People, Polymorphism, Single Nucleotide, White People, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Physiology (medical), medicine, Humans, CORONARY-HEART-DISEASE, HEMOSTASIS, Genetic Predisposition to Disease, Aged, 030304 developmental biology, business.industry, Heritability, GENOTYPES, MYOCARDIAL-INFARCTION, Genetic Loci, RISK-FACTORS, business
Abstract: Background— Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion ( Methods and Results— We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant ( P −8 ) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions— We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013

75. A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon Programme

Author: Alfred, T., Ben-Shlomo, Y., Cooper, R., Hardy, R., Gaunt, T.R., Gunnell, D., Harris, S.E., Kumari, M., Martin, R.M., Sayer, A.A., Starr, J.M., Kuh, D., Day, I.N.M., and The HALCyon study team
Abstract: Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.\ud \ud Methods :As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.\ud \ud Results: Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.\ud \ud Conclusion: Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
Published: 2012

76. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

Author: Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), Visscher, P.M. (Peter), Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), and Visscher, P.M. (Peter)
Abstract: Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10 -15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10 -5), 3.5% (P=10 -3) and 0.5% (P=6 × 10 -5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
Published: 2014
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77. Expression and function of Dlx genes in the osteoblast lineage

Author: Li, H., Marijanović, Inga, Kronenberg, M.S., Erceg, I., Stover, M.L., Velonis, D., Mina, M., Heinrich, J.G., Harris, S.E., Upholt, W.B., Kalajzić, Ivo, and Lichtler, A.C.
Subjects: musculoskeletal diseases, Distal-less homeobox proteins, Homeodomain Proteins, RNA, Messenger, Transcription Factors, embryonic structures
Abstract: Our laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5(-/-)/Dlx6(-/-) mice have more severe craniofacial and limb defects than Dlx5(-/-), some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5(-/-) mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function.
Published: 2008

78. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., BioBank Japan, Project, Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., Immunology, Medical Microbiology & Infectious Diseases, Erasmus MC other, Medical Informatics, Epidemiology, Pathology, Public Health, Ophthalmology, Internal Medicine, Cardiology, Child and Adolescent Psychiatry / Psychology, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U., Schurmann, Claudia, Smith, Albert V., Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D., Zhao, Wei, Bartz, Traci M., Concas, MARIA PINA, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I., O'Connel, Jeffrey R., Corre, Tanguy, Nongmaithem, Suraj S., Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki Eleni, Kacprowski, Tim, Bjonnes, Andrew, Van Der Spek, Ashley, Wu, Ying, Giri, Anil K., Yanek, Lisa R., Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A., Mcleod, Olga, Cornelis, Marilyn C., Pattaro, Cristian, Verweij, Niek, Baumbach, Clemen, Abdellaoui, Abdel, Warren, Helen R., Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John R. B., Cappellani, Stefania, Mirza, Saira S., Benton, Miles C., Broeckel, Ulrich, Medland, Sarah E., Lind, Penelope A., Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F., Zhi, Degui, Van Der Most, Peter J., Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaro, Van Der Laan, Sander W., Bradfield, Jonathan P., Wood, Andrew R., Bonnefond, Amelie, Ahluwalia, Tarunveer S., Hall, Leanne M., Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, De Haan, Hugoline G., Abney, Mark, Afzal, Uzma, Allison, Matthew A., Amin, Najaf, Asselbergs, Folkert W., Bakker, Stephan J. L., Barr, R. Graham, Baumeister, Sebastian E., Benjamin, Daniel J., Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P., Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J., Chen, Constance, Chen, Y. D. Ida, Collins, Francis S., Connell, John, Correa, Adolfo, Cupples, L. Adrienne, Smith, George Davey, Davies, Gail, Dörr, Marcu, Ehret, Georg, Ellis, Stephen B., Feenstra, Bjarke, Feitosa, Mary F., Ford, Ian, Fox, Caroline S., Frayling, Timothy M., Friedrich, Nele, Geller, Frank, Scotland, Generation, Gillham Nasenya, Irina, Gottesman, Omri, Graff, Misa, Grodstein, Francine, Gu, Charle, Haley, Chri, Hammond, Christopher J., Harris, Sarah E., Harris, Tamara B., Hastie, Nicholas D., Heard Costa, Nancy L., Heikkilä, Kauko, Hocking, Lynne J., Homuth, Georg, Hottenga, Jouke Jan, Huang, Jinyan, Huffman, Jennifer E., Hysi, Pirro G., Ikram, M. Arfan, Ingelsson, Erik, Joensuu, Anni, Johansson, Åsa, Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kanoni, Stavroula, Kerr, Shona M., Khan, Nazir M., Koellinger, Philipp, Koistinen, Heikki A., Kooner, Manraj K., Kubo, Michiaki, Kuusisto, Johanna, Lahti, Jari, Launer, Lenore J., Lea, Rodney A., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C. M., Lind, Lar, Loh, Marie, Lokki, Marja Liisa, London, Stephanie J., Loomis, Stephanie J., Loukola, Anu, Lu, Yingchang, Lumley, Thoma, Lundqvist, Annamari, Männistö, Satu, Marques Vidal, Pedro, Masciullo, Corrado, Matchan, Angela, Mathias, Rasika A., Matsuda, Koichi, Meigs, James B., Meisinger, Christa, Meitinger, Thoma, Menni, Cristina, Mentch, Frank D., Mihailov, Evelin, Milani, Lili, Montasser, May E., Montgomery, Grant W., Morrison, Alanna, Myers, Richard H., Nadukuru, Rajiv, Navarro, Pau, Nalis, Mari, Nieminen, Markku S., Nolte, Ilja M., O'Connor, George T., Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Pankow, James S., Patarcic, Inga, Pavani, Francesca, Peyser, Patricia A., Pietilainen, Kirsi, Poulter, Neil, Prokopenko, Inga, Ralhan, Sarju, Redmond, Paul, Rich, Stephen S., Rissanen, Harri, Robino, Antonietta, Rose, Lynda M., Rose, Richard, Sala, Cinzia, Salako, Babatunde, Salomaa, Veikko, Sarin, Antti Pekka, Saxena, Richa, Schmidt, Helena, Scott, Laura J., Scott, William R., Sennblad, Bengt, Seshadri, Sudha, Sever, Peter, Shrestha, Smeeta, Smith, Blair H., Smith, Jennifer A., Soranzo, Nicole, Sotoodehnia, Nona, Southam, Lorraine, Stanton, Alice V., Stathopoulou, Maria G., Strauch, Konstantin, Strawbridge, Rona J., Suderman, Matthew J., Tandon, Nikhil, Tang, Sian Tsun, Taylor, Kent D., Tayo, Bamidele O., Töglhofer, Anna Maria, Tomaszewski, Maciej, Tšernikova, Natalia, Tuomilehto, Jaakko, Uitterlinden, Andre G., Vaidya, Dhananjay, Van Hylckama Vlieg, Astrid, Van Setten, Jessica, Vasankari, Tuula, Vedantam, Sailaja, Vlachopoulou, Efthymia, Vozzi, Diego, Vuoksimaa, Eero, Waldenberger, Melanie, Ware, Erin B., Wentworth Shields, William, Whitfield, John B., Wild, Sarah, Willemsen, Gonneke, Yajnik, Chittaranjan S., Yao, Jie, Zaza, Gianluigi, Zhu, Xiaofeng, Salem, Rany M., Melbye, Mad, Bisgaard, Han, Samani, Nilesh J., Cusi, Daniele, Mackey, David A., Cooper, Richard S., Froguel, Philippe, Pasterkamp, Gerard, Grant, Struan F. A., Hakonarson, Hakon, Ferrucci, Luigi, Scott, Robert A., Morris, Andrew D., Palmer, Colin N. A., Dedoussis, George, Deloukas, Pano, Bertram, Lar, Lindenberger, Ulman, Berndt, Sonja I., Lindgren, Cecilia M., Timpson, Nicholas J., Tönjes, Anke, Munroe, Patricia B., Sørensen, Thorkild I. A., Rotimi, Charles N., Arnett, Donna K., Oldehinkel, Albertine J., Kardia, Sharon L. R., Balkau, Beverley, Gambaro, Giovanni, Morris, Andrew P., Eriksson, Johan G., Wright, Margie J., Martin, Nicholas G., Hunt, Steven C., Starr, John M., Deary, Ian J., Griffiths, Lyn R., Tiemeier, Henning, Pirastu, Nicola, Kaprio, Jaakko, Wareham, Nicholas J., Pérusse, Loui, Wilson, James G., Girotto, Giorgia, Caulfield, Mark J., Raitakari, Olli, Boomsma, Dorret I., Gieger, Christian, Van Der Harst, Pim, Hicks, Andrew A., Kraft, Peter, Sinisalo, Juha, Knekt, Paul, Johannesson, Magnu, Magnusson, Patrik K. E., Hamsten, Ander, Schmidt, Reinhold, Borecki, Ingrid B., Vartiainen, Erkki, Becker, Diane M., Bharadwaj, Dwaipayan, Mohlke, Karen L., Boehnke, Michael, Van Duijn, Cornelia M., Sanghera, Dharambir K., Teumer, Alexander, Zeggini, Eleftheria, Metspalu, Andre, Gasparini, Paolo, Ulivi, Sheila, Ober, Carole, Toniolo, Daniela, Rudan, Igor, Porteous, David J., Ciullo, Marina, Spector, Tim D., Hayward, Caroline, Dupuis, Josée, Loos, Ruth J. F., Wright, Alan F., Chandak, Giriraj R., Vollenweider, Peter, Shuldiner, Alan R., Ridker, Paul M., Rotter, Jerome I., Sattar, Naveed, Gyllensten, Ulf, North, Kari E., Pirastu, Mario, Psaty, Bruce M., Weir, David R., Laakso, Markku, Gudnason, Vilmundur, Takahashi, Atsushi, Chambers, John C., Kooner, Jaspal S., Strachan, David P., Campbell, Harry, Hirschhorn, Joel N., Perola, Marku, Polašek, Ozren, Wilson, James F., Imperial College Healthcare NHS Trust- BRC Funding, National Institute for Health Research, BioBank Japan, Project, The BioBank Japan Project, Ehret, Georg Benedikt, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Cardiovascular Centre (CVC)
Subjects: Male, Netherlands Twin Register (NTR), Blood Pressure, BLOOD-PRESSURE, INTELLIGENCE, Runs of Homozygosity, DISEASE, Homozygosity, Cohort Studies, Cognition, Forced Expiratory Volume, GENETIC-VARIANTS, Inbreeding depression, Settore MED/14 - NEFROLOGIA, Inbreeding, Inbreeding, Evolutionary genetics, Quantitative trait loci, Non-U.S. Gov't, Dominance (genetics), ddc:616, Genetics, ARCHITECTURE, Genome, Multidisciplinary, Body Height/genetics, Research Support, Non-U.S. Gov't, Homozygote, Confounding, heterozygosity, inbreeding, genomics, QUANTITATIVE TRAITS, BioBank Japan Project, Biological Evolution, Multidisciplinary Sciences, Cholesterol, Phenotype, Cholesterol, LDL/genetics, Trait, Science & Technology - Other Topics, Educational Status, Female, Lung Volume Measurements, Human, INBREEDING DEPRESSION, Quantitative trait loci, Blood Pressure/genetics, General Science & Technology, Forced Expiratory Volume/genetics, Lung Volume Measurement, Quantitative trait locus, Biology, Research Support, Evolutionary genetics, Article, LDL, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Journal Article, Humans, Genetic association, Science & Technology, Genome, Human, ta1184, PATHWAYS, Cholesterol, LDL, Body Height, Educational Statu, ASSOCIATION ANALYSIS, Evolutionary biology, Genome, Human/genetics, ta1181, Cohort Studie, Meta-Analysis
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
Published: 2015

79. Nonreciprocal Emissive and Absorptive Processes

Author: Harris, S.E., primary, Imamoglu, A., additional, and Macklin, J.J., additional
Published: 1989
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80. CCL7 Is a Protective Factor Secreted by Mechanically Loaded Osteocytes

Author: Kitase, Y., primary, Lee, S., additional, Gluhak-Heinrich, J., additional, Johnson, M.L., additional, Harris, S.E., additional, and Bonewald, L.F., additional
Published: 2014
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81. The SNAP spectrograph

Author: Ealet, A., Bebek, C., Akerlof, C.W., Aldering, G., Amanullah, R., Astier, P., Barrelet, E., Bergstrom, L., Bercovitz, J., Bernstein, G.M., Bester, M., Bonissent, A., Bower, C.R., Carithers, W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R.S., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J.-F., Goldhaber, G., Goobar, A., Groom, D.E., Harris, S.E., Harvey, P.R., Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kim, A.G., Kolbe, W.F., Kireger, B., Lafever, R., Lamoureux, J., Lampton, M., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.M., Miquel, R., Moertsell, E., Mostek, N., Mufson, S., Musser, J.A., Nugent, P.E., Oluseyi, H.M., Pain, R., Palaio, N.P., Pankow, D.H., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K.E., Roe, N., Sholl, M., Schnubnell, M.S., Smadja, G., Smoot, G.F., Spadafora, A., Tarle, G., Tomasch, A.D., Von Der Lippe, H., Vincent, D., Walder, J.-P., Wang, Gang, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and Flores, Sylvie
Subjects: [PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], [PHYS.ASTR.CO] Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Astrophysics::High Energy Astrophysical Phenomena, Astrophysics::Solar and Stellar Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, [SDU.ASTR] Sciences of the Universe [physics]/Astrophysics [astro-ph], Astrophysics::Galaxy Astrophysics
Abstract: Supernovae
Published: 2002

82. Seventy-five genetic loci influencing the human red blood cell

Author: van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., Nauck, M., et al., van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., and Nauck, M., et al.
Abstract: Item does not contain fulltext, Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Published: 2012

83. The ATXN1 and TRIM31 genes are related to intelligence in an ADHD background: evidence from a large collaborative study totaling 4,963 subjects

Author: Rizzi, T.S., Arias Vasquez, A., Rommelse, N.N.J., Kuntsi, J., Anney, R., Asherson, P., Buitelaar, J.K., Banaschewski, T., Ebstein, R., Ruano, D., Sluis, S. Van der, Markunas, C.A., Garrett, M.E., Ashley-Koch, A.E., Kollins, S.H., Anastopoulos, A.D., Hansell, N.K., Wright, M.J., Montgomery, G.W., Martin, N.G., Harris, S.E., Davies, G., Tenesa, A., Porteous, D.J., Starr, J.M., Deary, I.J., St Pourcain, B., Davey Smith, G., Timpson, N.J., Evans, D.M., Gill, M., Miranda, A., Mulas, F., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J.A., Sonuga-Barke, E.J.S., Steinhausen, H.C., Taylor, E., Faraone, S.V., Franke, B., Posthuma, D., Rizzi, T.S., Arias Vasquez, A., Rommelse, N.N.J., Kuntsi, J., Anney, R., Asherson, P., Buitelaar, J.K., Banaschewski, T., Ebstein, R., Ruano, D., Sluis, S. Van der, Markunas, C.A., Garrett, M.E., Ashley-Koch, A.E., Kollins, S.H., Anastopoulos, A.D., Hansell, N.K., Wright, M.J., Montgomery, G.W., Martin, N.G., Harris, S.E., Davies, G., Tenesa, A., Porteous, D.J., Starr, J.M., Deary, I.J., St Pourcain, B., Davey Smith, G., Timpson, N.J., Evans, D.M., Gill, M., Miranda, A., Mulas, F., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J.A., Sonuga-Barke, E.J.S., Steinhausen, H.C., Taylor, E., Faraone, S.V., Franke, B., and Posthuma, D.
Abstract: Contains fulltext : 96400.pdf (publisher's version ) (Closed access), Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder.
Published: 2011

84. Genetic predictors of fibrin D-dimer levels in healthy adults

Author: Smith, N.L. (Nicholas), Huffman, J.E. (Jennifer E.), Strachan, D.P. (David), Huang, J. (Jian), Dehghan, A. (Abbas), Trompet, S. (Stella), Lopez, L.M. (Lorna M.), Shin, S.Y. (So Youn), Baumert, J. (Jens), Vitart, V. (Veronique), Bis, J.C. (Joshua), Wild, S.H. (Sarah), Rumley, A. (Ann), Yang, Q. (Qiong Fang), Uitterlinden, A.G. (André), Stott, D.J. (David. J.), Davies, G. (Gareth), Carter, A.M. (Angela M.), Thorand, B. (Barbara), Polašek, O. (Ozren), McKnight, B. (Barbara), Campbell, H. (Harry), Rudnicka, A.R. (Alicja), Chen, M.H. (Min-hsin), Buckley, B.M. (Brendan M.), Harris, S.E. (Sarah), Peters, A. (Annette), Pulanic, D. (Drazen), Lumley, T. (Thomas), de Craen, A.J.M. (Anton J.M.), Liewald, D.C.M. (David), Gieger, C. (Christian), Ford, I. (Ian), Gow, A.J. (Alan J.), Luciano, M. (Michelle), Porteous, D.J. (David J.), Guo, X. (Xiuqing), Sattar, N. (Naveed), Tenesa, A. (Albert), Cushman, M. (Mary Ann), Slagboom, P.E. (Eline), Visscher, P.M. (Peter M.), Spector, T.D. (Timothy), Illig, T. (Thomas), Rudan, I. (Igor), Bovill, E.G. (Edwin G.), Wright, A.F. (Alan), McArdle, W.L. (Wendy), Tofler, G.H. (Geoffrey), Hofman, A. (Albert), Westendorp, R.G.J. (Rudi), Starr, J.M. (John), Grant, P.J. (Peter J.), Karakas, M. (Mahir), Hastie, N.D. (Nicholas D.), Psaty, B.M. (Bruce), Wilson, J.F. (James), Lowe, G.D.O. (Gordon), O'Donnell, C.J. (Christopher), Witteman, J.C.M. (Jacqueline), Jukema, J.W. (Jan Wouter), Deary, I.J. (Ian), Soranzo, N. (Nicole), Koenig, W. (Wolfgang), Hayward, C. (Caroline), Smith, N.L. (Nicholas), Huffman, J.E. (Jennifer E.), Strachan, D.P. (David), Huang, J. (Jian), Dehghan, A. (Abbas), Trompet, S. (Stella), Lopez, L.M. (Lorna M.), Shin, S.Y. (So Youn), Baumert, J. (Jens), Vitart, V. (Veronique), Bis, J.C. (Joshua), Wild, S.H. (Sarah), Rumley, A. (Ann), Yang, Q. (Qiong Fang), Uitterlinden, A.G. (André), Stott, D.J. (David. J.), Davies, G. (Gareth), Carter, A.M. (Angela M.), Thorand, B. (Barbara), Polašek, O. (Ozren), McKnight, B. (Barbara), Campbell, H. (Harry), Rudnicka, A.R. (Alicja), Chen, M.H. (Min-hsin), Buckley, B.M. (Brendan M.), Harris, S.E. (Sarah), Peters, A. (Annette), Pulanic, D. (Drazen), Lumley, T. (Thomas), de Craen, A.J.M. (Anton J.M.), Liewald, D.C.M. (David), Gieger, C. (Christian), Ford, I. (Ian), Gow, A.J. (Alan J.), Luciano, M. (Michelle), Porteous, D.J. (David J.), Guo, X. (Xiuqing), Sattar, N. (Naveed), Tenesa, A. (Albert), Cushman, M. (Mary Ann), Slagboom, P.E. (Eline), Visscher, P.M. (Peter M.), Spector, T.D. (Timothy), Illig, T. (Thomas), Rudan, I. (Igor), Bovill, E.G. (Edwin G.), Wright, A.F. (Alan), McArdle, W.L. (Wendy), Tofler, G.H. (Geoffrey), Hofman, A. (Albert), Westendorp, R.G.J. (Rudi), Starr, J.M. (John), Grant, P.J. (Peter J.), Karakas, M. (Mahir), Hastie, N.D. (Nicholas D.), Psaty, B.M. (Bruce), Wilson, J.F. (James), Lowe, G.D.O. (Gordon), O'Donnell, C.J. (Christopher), Witteman, J.C.M. (Jacqueline), Jukema, J.W. (Jan Wouter), Deary, I.J. (Ian), Soranzo, N. (Nicole), Koenig, W. (Wolfgang), and Hayward, C. (Caroline)
Abstract: BACKGROUND: Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. METHODS AND RESULTS: A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between ≈2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log-transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4×10) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4×10) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9×10) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log-transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. CONCLUSIONS: Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported.
Published: 2011
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85. Inorganic phosphate stimulates DMP1 expression in human periodontal ligament fibroblasts embedded in three-dimensional collagen gels.

Author: Berendsen, A.D., Smit, T.H., Schoenmaker, T., Walboomers, X.F., Harris, S.E., Everts, V., Bronckers, A.L., Berendsen, A.D., Smit, T.H., Schoenmaker, T., Walboomers, X.F., Harris, S.E., Everts, V., and Bronckers, A.L.
Abstract: Item does not contain fulltext, Stable integration of collagenous tissue-engineered constructs to surrounding solid devices can be accomplished by coating the solid surfaces with exogenous alkaline phosphatase (ALP). We showed previously that coating of culture well surfaces with the enzyme in combination with the presence of its substrate beta-glycerophosphate (beta-GP) induces mineral deposition at the interface of matrix and surface, thereby preventing matrix detachment. In this study the effect of such mineral-inducing conditions on differentiation of human periodontal ligament (PDL) fibroblasts into osteoblasts/cementoblasts was analyzed in three-dimensional collagen gels. Mineral-inducing conditions decreased collagen type I gene expression and induced dentin matrix protein 1 (DMP1; a marker of late osteoblasts/cementoblasts) gene expression by fibroblasts. DMP1 protein was detected in some fibroblasts only in mineralizing gels. Exogenous ALP released high levels of inorganic phosphate from beta-GP. Addition of inorganic phosphate alone induced DMP1 gene expression, which could be prevented by blocking phosphate entry into fibroblasts by foscarnet. We concluded that mineralizing conditions induced by exogenous ALP affect the phenotype of PDL fibroblasts. The fibroblasts are stimulated to express the late osteoblast/osteocyte marker protein DMP1, which is mediated by uptake of inorganic phosphate into the cells. The enzyme-mediated mineral deposition may thus facilitate enhanced integration of collagenous tissue-engineered constructs to devices or implants in vitro.
Published: 2010

86. Modulation of Photons and Biphotons

Author: Harris, S.E., Belthangady, Chinmay, Chuu, Chih-Sung, Du, Shengwang, Kolchin, P., Sensarn, S., Yu, I.A., Kahn, J.M., Yin, G.Y., Harris, S.E., Belthangady, Chinmay, Chuu, Chih-Sung, Du, Shengwang, Kolchin, P., Sensarn, S., Yu, I.A., Kahn, J.M., and Yin, G.Y.
Published: 2010

87. Modulation and measurement of time-energy entangled photons

Author: Belthangady, Chinmay, Du, Shengwang, Chuu, Chih-Sung, Yin, G.Y., Harris, S.E., Belthangady, Chinmay, Du, Shengwang, Chuu, Chih-Sung, Yin, G.Y., and Harris, S.E.
Published: 2009

88. A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly

Author: Bochdanovits, Z., Gosso, M.F., van den Berg, L., Rizzu, P., Polderman, T.J.C., Pardo, L.M., Houlihan, L.M., Luciano, M., Starr, J.M., Harris, S.E., Deary, I.J., de Geus, E.J.C., Boomsma, D.I., Heutink, P., Posthuma, D., Bochdanovits, Z., Gosso, M.F., van den Berg, L., Rizzu, P., Polderman, T.J.C., Pardo, L.M., Houlihan, L.M., Luciano, M., Starr, J.M., Harris, S.E., Deary, I.J., de Geus, E.J.C., Boomsma, D.I., Heutink, P., and Posthuma, D.
Abstract: Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior. © 2008 Springer Science+Business Media, LLC.
Published: 2009
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89. Observation of Optical Precursors at the Biphoton Level

Author: Du, Shengwang, Belthangady, Chinmay, Kolchin, Pavel, Yin, G.Y., Harris, S.E., Du, Shengwang, Belthangady, Chinmay, Kolchin, Pavel, Yin, G.Y., and Harris, S.E.
Published: 2008

90. Single photons with arbitrary waveforms

Author: Kolchin, Pavel, Belthangady, Chinmay, Du, Shengwang, Yin, G.Y., Harris, S.E., Kolchin, Pavel, Belthangady, Chinmay, Du, Shengwang, Yin, G.Y., and Harris, S.E.
Published: 2008

91. Measurement of biphoton wavefunctions using fast amplitude modulators

Author: Belthangady, Chinmay, Du, Shengwang, Pavel, Kolchin, Yin, G.Y., Harris, S.E., Belthangady, Chinmay, Du, Shengwang, Pavel, Kolchin, Yin, G.Y., and Harris, S.E.
Published: 2008

92. Generation of biphotons with controllable temporal length

Author: Belthangady, Chinmay, Du, Shengwang, Kolchin, Pavel, Yin, G.Y., Harris, S.E., Belthangady, Chinmay, Du, Shengwang, Kolchin, Pavel, Yin, G.Y., and Harris, S.E.
Published: 2008

93. Testing replication of a 5-SNP set for general cognitive ability in six population samples.

Author: Luciano, M., Lind, P.A., Deary, I.J., Payton, A., Posthuma, D., Butcher, L.M., Bochdanovits, Z., Whalley, L.J., Visscher, P.M., Harris, S.E., Polderman, T.J.C., Davis, O.S.P., Wright, M.J., Starr, J.M., de Geus, E.J.C., Bates, T.C., Montgomery, GW, Boomsma, D.I., Martin, N.G., Plomin, R., Luciano, M., Lind, P.A., Deary, I.J., Payton, A., Posthuma, D., Butcher, L.M., Bochdanovits, Z., Whalley, L.J., Visscher, P.M., Harris, S.E., Polderman, T.J.C., Davis, O.S.P., Wright, M.J., Starr, J.M., de Geus, E.J.C., Bates, T.C., Montgomery, GW, Boomsma, D.I., Martin, N.G., and Plomin, R.
Abstract: A 5-single nucleotide polymorphism (SNP) set has been associated with general cognitive ability in 5000 7-year-old children from the Twins Early Development Study (TEDS). Four of these SNPs were identified through a 10K microarray analysis and one was identified through a targeted analysis of brain-expressed genes. The present study tested this association with general cognitive ability in six population samples of varying size and age from Australia, the UK (Scotland and England) and the Netherlands. Results from the largest sample (N=1310) approached significance (P = 0.06) in the direction of the original finding, but results from the other samples (N = 205-758) were mixed. A meta-analysis of the results - allowing for effect size heterogeneity between samples - yielded a non-significant correlation (r = -0.01, P = 0.57), indicating that this SNP set was not associated with general cognitive ability in the populations studied.
Published: 2008
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94. Bmp2 gene in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Author: Yang, W., primary, Guo, D., additional, Harris, M.A., additional, Cui, Y., additional, Gluhak-Heinrich, J., additional, Wu, J., additional, Chen, X.-D., additional, Skinner, C, additional, Nyman, J., additional, Edwards, J.R., additional, Mundy, G.R., additional, Lichtler, A., additional, Kream, B., additional, Rowe, D., additional, Kalajzic, I., additional, David, V., additional, Quarles, D., additional, Villareal, D., additional, Scott, Greg, additional, Ray, Manas, additional, Liu, S., additional, Martin, J.F., additional, Mishina, Y., additional, and Harris, S.E., additional
Published: 2013
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95. X-ray / Optical Sum Frequency Generation

Author: Glover, T.E., primary, Fritz, D.M., additional, Cammarata, M., additional, Allison, T.K., additional, Coh, Sinisa, additional, Feldkamp, J.M., additional, Lemke, H., additional, Zhu, D., additional, Feng, Y., additional, Coffee, R.N., additional, Fuchs, M., additional, Ghimire, S., additional, Chen, J., additional, Shwartz, S., additional, Reis, D.A., additional, Harris, S.E., additional, and Hastings, J. B., additional
Published: 2013
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96. Generation of Subnatural Linewidth Biphotons

Author: Du, Shengwang, Belthangady, Chinmay, Kolchin, Pavel, Yin, G.Y., Harris, S.E., Du, Shengwang, Belthangady, Chinmay, Kolchin, Pavel, Yin, G.Y., and Harris, S.E.
Published: 2007

97. The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

Author: Mekel-Bobrov, N., Posthuma, D., Gilbert, S.L., Lind, P., Gosso, M.F., Luciano, M., Harris, S.E., Bates, T.C., Polderman, T.J.C., Whalley, L.J., Fox, H., Starr, J.M., Evans, P.D., Montgomery, GW, Fernandes, C., Heutink, P., Martin, N.G., Boomsma, D.I., Deary, I.J., Wright, M.J., de Geus, E.J.C., Lahn, B.T., Mekel-Bobrov, N., Posthuma, D., Gilbert, S.L., Lind, P., Gosso, M.F., Luciano, M., Harris, S.E., Bates, T.C., Polderman, T.J.C., Whalley, L.J., Fox, H., Starr, J.M., Evans, P.D., Montgomery, GW, Fernandes, C., Heutink, P., Martin, N.G., Boomsma, D.I., Deary, I.J., Wright, M.J., de Geus, E.J.C., and Lahn, B.T.
Abstract: Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype. © 2007 Oxford University Press.
Published: 2007
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98. Generation of Narrow Bandwidth Paired Photons: Use of A Single Driving Laser

Author: Du, Shengwang, Kolchin, Pavel, Belthangady, Chinmay, Yin, G.Y., Harris, S.E., Du, Shengwang, Kolchin, Pavel, Belthangady, Chinmay, Yin, G.Y., and Harris, S.E.
Published: 2006

99. Bmp2 Is Required for Odontoblast Differentiation and Pulp Vasculogenesis

Author: Yang, W., primary, Harris, M.A., additional, Cui, Y., additional, Mishina, Y., additional, Harris, S.E., additional, and Gluhak-Heinrich, J., additional
Published: 2011
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100. X-ray / Optical Wave Mixing

Author: Glover, T.E., primary, Allison, T.K., additional, Cammarata, M., additional, Feldkamp, J., additional, Fritz, D.M., additional, Hastings, J.B., additional, Harris, S.E., additional, Reis, D.A., additional, and Schwarz, S., additional
Published: 2011
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