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

Author

Benyamin, B, Pourcain, BSt, Davis, O S, Davies, G, Hansell, N K, Brion, M-JA, Kirkpatrick, R M, Cents, R A M, Franić, S, Miller, M B, Haworth, C M A, Meaburn, E, Price, T S, Evans, D M, Timpson, N, Kemp, J, Ring, S, McArdle, W, Medland, S E, Yang, J, Harris, S E, Liewald, D C, Scheet, P, Xiao, X, Hudziak, J J, de Geus, E J C, Jaddoe, V W V, Starr, J M, Verhulst, F C, Pennell, C, Tiemeier, H, Iacono, W G, Palmer, L J, Montgomery, G W, Martin, N G, Boomsma, D I, Posthuma, D, McGue, M, Wright, M J, Davey Smith, G, Deary, I J, Plomin, R, and Visscher, P M

Published
2014
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24. Baseline brain function in the preadolescents of the ABCD Study

Author

Chaarani, B., Hahn, S., Allgaier, N., Adise, S., Owens, M. M., Juliano, A. C., Yuan, D. K., Loso, H., Ivanciu, A., Albaugh, M. D., Dumas, J., Mackey, S., Laurent, J., Ivanova, M., Hagler, D. J., Cornejo, M. D., Hatton, S., Agrawal, A., Aguinaldo, L., Ahonen, L., Aklin, W., Anokhin, A. P., Arroyo, J., Avenevoli, S., Babcock, D., Bagot, K., Baker, F. C., Banich, M. T., Barch, D. M., Bartsch, H., Baskin-Sommers, A., Bjork, J. M., Blachman-Demner, D., Bloch, M., Bogdan, R., Bookheimer, S. Y., Breslin, F., Brown, S., Calabro, F. J., Calhoun, V., Casey, B. J., Chang, L., Clark, D. B., Cloak, C., Constable, R. T., Constable, K., Corley, R., Cottler, L. B., Coxe, S., Dagher, R. K., Dale, A. M., Dapretto, M., Delcarmen-Wiggins, R., Dick, A. S., Do, E. K., Dosenbach, N. U. F., Dowling, G. J., Edwards, S., Ernst, T. M., Fair, D. A., Fan, C. C., Feczko, E., Feldstein-Ewing, S. W., Florsheim, P., Foxe, J. J., Freedman, E. G., Friedman, N. P., Friedman-Hill, S., Fuemmeler, B. F., Galvan, A., Gee, D. G., Giedd, J., Glantz, M., Glaser, P., Godino, J., Gonzalez, M., Gonzalez, R., Grant, S., Gray, K. M., Haist, F., Harms, M. P., Hawes, S., Heath, A. C., Heeringa, S., Heitzeg, M. M., Hermosillo, R., Herting, M. M., Hettema, J. M., Hewitt, J. K., Heyser, C., Hoffman, E., Howlett, K., Huber, R. S., Huestis, M. A., Hyde, L. W., Iacono, W. G., Infante, M. A., Irfanoglu, O., Isaiah, A., Iyengar, S., Jacobus, J., James, R., Jean-Francois, B., Jernigan, T., Karcher, N. R., Kaufman, A., Kelley, B., Kit, B., Ksinan, A., Kuperman, J., Laird, A. R., Larson, C., LeBlanc, K., Lessov-Schlagger, C., Lever, N., Lewis, D. A., Lisdahl, K., Little, A. R., Lopez, M., Luciana, M., Luna, B., Madden, P. A., Maes, H. H., Makowski, C., Marshall, A. T., Mason, M. J., Matochik, J., McCandliss, B. D., McGlade, E., Montoya, I., Morgan, G., Morris, A., Mulford, C., Murray, P., Nagel, B. J., Neale, M. C., Neigh, G., Nencka, A., Noronha, A., Nixon, S. J., Palmer, C. E., Pariyadath, V., Paulus, M. P., Pelham, W. E., Pfefferbaum, D., Pierpaoli, C., Prescot, A., Prouty, D., Puttler, L. I., Rajapaske, N., Rapuano, K. M., Reeves, G., Renshaw, P. F., Riedel, M. C., Rojas, P., de la Rosa, M., Rosenberg, M. D., Ross, M. J., Sanchez, M., Schirda, C., Schloesser, D., Schulenberg, J., Sher, K. J., Sheth, C., Shilling, P. D., Simmons, W. K., Sowell, E. R., Speer, N., Spittel, M., Squeglia, L. M., Sripada, C., Steinberg, J., Striley, C., Sutherland, M. T., Tanabe, J., Tapert, S. F., Thompson, W., Tomko, R. L., Uban, K. A., Vrieze, S., Wade, N. E., Watts, R., Weiss, S., Wiens, B. A., Williams, O. D., Wilbur, A., Wing, D., Wolff-Hughes, D., Yang, R., Yurgelun-Todd, D. A., Zucker, R. A., Potter, A., and Garavan, H. P.

Abstract

The Adolescent Brain Cognitive Development (ABCD) Study®is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N= 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N= 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N= 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Published
2021
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25. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Author

Stringer, S., Minică, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., van Eijk, K. R., Isen, J. D., Loukola, A., Maciejewski, D. F., Mihailov, E., van der Most, P. J., Sánchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J. J., Abdellaoui, A., Bigdeli, T. B., Branje, S. J. T., Brown, S. A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martínez, Iris, Gordon, Scott D., Harris, J. M., Hartman, C. A., Henders, A. K., Heath, A. C., Hickie, Ian B., Hickman, M., Hopfer, C. J., Hottenga, J. J., Huizink, A. C., Irons, D. E., Kahn, R. S., Korhonen, T., Kranzler, H. R., Krauter, K., van Lier, P. A. C., Lubke, G. H., Madden, P. A. F., Mägi, Reedik, McGue, M. K., Medland, S. E., Meeus, W. H. J., Miller, M. B., Montgomery, G. W., Nivard, M. G., Nolte, I M., Oldehinkel, A. J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, Josep Antoni, Richarte, Vanesa, Rose, R. J., Shin, J., Stallings, M. C., Stiby, A. I, Wall, T. L., Wright, M. J., Koot, H. M., Paus, T., Hewitt, J. K., Ribasés, M., Kaprio, J., Boks, M. P., Snieder, Harold, Spector, T., Munafò, M. R., Metspalu, A., Gelernter, J., Boomsma, D. I, Iacono, W. G., Martin, N. G., Gillespie, N. A., Derks, E. M., Vink, J. M., and Universitat Autònoma de Barcelona

Abstract

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N =32 330) and four replication samples (N =5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P

Published
2016

26. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Author

Stringer, S, Minică, C C, Verweij, K J H, Mbarek, H, Bernard, M, Derringer, J, van Eijk, K R, Isen, J D, Loukola, A, Maciejewski, D F, Mihailov, E, van der Most, P J, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, J J, Abdellaoui, A, Bigdeli, T B, Branje, S J T, Brown, S A, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, S D, Harris, J M, Hartman, C A, Henders, A K, Heath, A C, Hickie, Ian B, Hickman, M, Hopfer, C J, Hottenga, J J, Huizink, A C, Irons, D E, Kahn, R S, Korhonen, T, Kranzler, H R, Krauter, K, van Lier, P A C, Lubke, G H, Madden, P A F, Mägi, R, McGue, M K, Medland, S E, Meeus, W H J, Miller, M B, Montgomery, G W, Nivard, M G, Nolte, I M, Oldehinkel, A J, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, J A, Richarte, V, Rose, R J, Shin, J, Stallings, M C, Stiby, A I, Wall, T L, Wright, M J, Koot, H M, Paus, T, Hewitt, J K, Ribasés, M, Kaprio, J, Boks, M P, Snieder, Harold, Spector, T, Munafò, M R, Metspalu, A, Gelernter, J, Boomsma, D I, Iacono, W G, Martin, N G, Gillespie, N A, Derks, E M, Vink, J M, and Universitat Autònoma de Barcelona

Abstract

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N =32 330) and four replication samples (N =5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P

Published
2016

28. Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders

Author

Venables, N. C., Hicks, B. M, Yancey, J. R., Kramer, Mark, Nelson, L. D., Strickland, C. M., Krueger, R. F., Iacono, W. G., Patrick, C. J., Venables, N. C., Hicks, B. M, Yancey, J. R., Kramer, Mark, Nelson, L. D., Strickland, C. M., Krueger, R. F., Iacono, W. G., and Patrick, C. J.

Abstract

Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N = 454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology., Funding Agencies:United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) P50 MH072850RC1 MH089727United States Department of Defense W911NF-14-1-0027

Published
2017
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29. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, Stringer, S., Minica, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., van Eijk, K. R., Isen, J. D., Loukola, A., Maciejewski, D. F., Mihailov, E., van der Most, P. J., Sanchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J. J., Abdellaoui, A., Bigdeli, T. B., Branje, S. J. T., Brown, S. A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S. D., Harris, J. M., Hartman, C. A., Henders, A. K., Heath, A. C., Hickie, I. B., Hickman, M., Hopfer, C. J., Hottenga, J. J., Huizink, A. C., Irons, D. E., Kahn, R. S., Korhonen, T., Kranzler, H. R., Krauter, K., van Lier, P. A. C., Lubke, G. H., Madden, P. A. F., Magi, R., McGue, M. K., Medland, S. E., Meeus, W. H. J., Miller, M. B., Montgomery, G. W., Nivard, M. G., Nolte, I. M., Oldehinkel, A. J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J. A., Richarte, V., Rose, R. J., Shin, J., Stallings, M. C., Stiby, A. I., Wall, T. L., Wright, M. J., Koot, H. M., Paus, T., Hewitt, J. K., Ribases, M., Kaprio, J., Boks, M. P., Snieder, H., Spector, T., Munafo, M. R., Metspalu, A., Gelernter, J., Boomsma, D. I., Iacono, W. G., Martin, N. G., Gillespie, N. A., Derks, E. M., Vink, J. M., University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, Stringer, S., Minica, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., van Eijk, K. R., Isen, J. D., Loukola, A., Maciejewski, D. F., Mihailov, E., van der Most, P. J., Sanchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J. J., Abdellaoui, A., Bigdeli, T. B., Branje, S. J. T., Brown, S. A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S. D., Harris, J. M., Hartman, C. A., Henders, A. K., Heath, A. C., Hickie, I. B., Hickman, M., Hopfer, C. J., Hottenga, J. J., Huizink, A. C., Irons, D. E., Kahn, R. S., Korhonen, T., Kranzler, H. R., Krauter, K., van Lier, P. A. C., Lubke, G. H., Madden, P. A. F., Magi, R., McGue, M. K., Medland, S. E., Meeus, W. H. J., Miller, M. B., Montgomery, G. W., Nivard, M. G., Nolte, I. M., Oldehinkel, A. J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J. A., Richarte, V., Rose, R. J., Shin, J., Stallings, M. C., Stiby, A. I., Wall, T. L., Wright, M. J., Koot, H. M., Paus, T., Hewitt, J. K., Ribases, M., Kaprio, J., Boks, M. P., Snieder, H., Spector, T., Munafo, M. R., Metspalu, A., Gelernter, J., Boomsma, D. I., Iacono, W. G., Martin, N. G., Gillespie, N. A., Derks, E. M., and Vink, J. M.

Abstract

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N = 32 330) and four replication samples (N = 5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use.

Published
2016

30. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Author

Adolescent development: Characteristics and determinants, Afd culturele antropologie, Leerstoel Branje, Leerstoel Meeus, Sub Biomol.Mass Spectrometry & Proteom., Sub High energy Astrophysics begr 1/1/15, Stringer, S, Minică, C C, Verweij, K J H, Mbarek, H, Bernard, M, Derringer, J, van Eijk, K R, Isen, J D, Loukola, A, Maciejewski, Dominique F., Mihailov, E, van der Most, P J, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, J J, Abdellaoui, A, Bigdeli, T B, Branje, S J T, Brown, S A, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, S D, Harris, J M, Hartman, C A, Henders, A K, Heath, A C, Hickie, I B, Hickman, M, Hopfer, C J, Hottenga, J J, Huizink, A C, Irons, D E, Kahn, R S, Korhonen, T, Kranzler, H R, Krauter, K, van Lier, P A C, Lubke, G H, Madden, P A F, Mägi, R, McGue, M K, Medland, S E, Meeus, W H J, Miller, M B, Montgomery, G W, Nivard, M G, Nolte, I M, Oldehinkel, A J, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, J A, Richarte, V, Rose, R J, Shin, J, Stallings, M C, Stiby, A I, Wall, T L, Wright, M J, Koot, H M, Paus, T, Hewitt, J K, Ribasés, M, Kaprio, J, Boks, M P, Snieder, H, Spector, T, Munafò, M R, Metspalu, A, Gelernter, J, Boomsma, D I, Iacono, W G, Martin, N G, Gillespie, N A, Derks, E M, Vink, J M, Adolescent development: Characteristics and determinants, Afd culturele antropologie, Leerstoel Branje, Leerstoel Meeus, Sub Biomol.Mass Spectrometry & Proteom., Sub High energy Astrophysics begr 1/1/15, Stringer, S, Minică, C C, Verweij, K J H, Mbarek, H, Bernard, M, Derringer, J, van Eijk, K R, Isen, J D, Loukola, A, Maciejewski, Dominique F., Mihailov, E, van der Most, P J, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, J J, Abdellaoui, A, Bigdeli, T B, Branje, S J T, Brown, S A, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, S D, Harris, J M, Hartman, C A, Henders, A K, Heath, A C, Hickie, I B, Hickman, M, Hopfer, C J, Hottenga, J J, Huizink, A C, Irons, D E, Kahn, R S, Korhonen, T, Kranzler, H R, Krauter, K, van Lier, P A C, Lubke, G H, Madden, P A F, Mägi, R, McGue, M K, Medland, S E, Meeus, W H J, Miller, M B, Montgomery, G W, Nivard, M G, Nolte, I M, Oldehinkel, A J, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, J A, Richarte, V, Rose, R J, Shin, J, Stallings, M C, Stiby, A I, Wall, T L, Wright, M J, Koot, H M, Paus, T, Hewitt, J K, Ribasés, M, Kaprio, J, Boks, M P, Snieder, H, Spector, T, Munafò, M R, Metspalu, A, Gelernter, J, Boomsma, D I, Iacono, W G, Martin, N G, Gillespie, N A, Derks, E M, and Vink, J M

Published
2016

31. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium

Author

Stringer, S., Minica, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., van Eijk, K. R., Isen, J. D., Loukola, A., Maciejewski, D. F., Mihailov, E., van der Most, P. J., Sanchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J. J., Abdellaoui, A., Bigdeli, T. B., Branje, S. J. T., Brown, S. A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S. D., Harris, J. M., Hartman, C. A., Henders, A. K., Heath, A. C., Hickie, I. B., Hickman, M., Hopfer, C. J., Hottenga, J. J., Huizink, A. C., Irons, D. E., Kahn, R. S., Korhonen, T., Kranzler, H. R., Krauter, K., van Lier, P. A. C., Lubke, G. H., Madden, P. A. F., Magi, R., McGue, M. K., Medland, S. E., Meeus, W. H. J., Miller, M. B., Montgomery, G. W., Nivard, M. G., Nolte, I. M., Oldehinkel, A. J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J. A., Richarte, V., Rose, R. J., Shin, J., Stallings, M. C., Stiby, A. I., Wall, T. L., Wright, M. J., Koot, H. M., Paus, T., Hewitt, J. K., Ribases, M., Kaprio, J., Boks, M. P., Snieder, H., Spector, T., Munafo, M. R., Metspalu, A., Gelernter, J., Boomsma, D. I., Iacono, W. G., Martin, N. G., Gillespie, N. A., Derks, E. M., Vink, J. M., Stringer, S., Minica, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., van Eijk, K. R., Isen, J. D., Loukola, A., Maciejewski, D. F., Mihailov, E., van der Most, P. J., Sanchez-Mora, C., Roos, L., Sherva, R., Walters, R., Ware, J. J., Abdellaoui, A., Bigdeli, T. B., Branje, S. J. T., Brown, S. A., Bruinenberg, M., Casas, M., Esko, T., Garcia-Martinez, I., Gordon, S. D., Harris, J. M., Hartman, C. A., Henders, A. K., Heath, A. C., Hickie, I. B., Hickman, M., Hopfer, C. J., Hottenga, J. J., Huizink, A. C., Irons, D. E., Kahn, R. S., Korhonen, T., Kranzler, H. R., Krauter, K., van Lier, P. A. C., Lubke, G. H., Madden, P. A. F., Magi, R., McGue, M. K., Medland, S. E., Meeus, W. H. J., Miller, M. B., Montgomery, G. W., Nivard, M. G., Nolte, I. M., Oldehinkel, A. J., Pausova, Z., Qaiser, B., Quaye, L., Ramos-Quiroga, J. A., Richarte, V., Rose, R. J., Shin, J., Stallings, M. C., Stiby, A. I., Wall, T. L., Wright, M. J., Koot, H. M., Paus, T., Hewitt, J. K., Ribases, M., Kaprio, J., Boks, M. P., Snieder, H., Spector, T., Munafo, M. R., Metspalu, A., Gelernter, J., Boomsma, D. I., Iacono, W. G., Martin, N. G., Gillespie, N. A., Derks, E. M., and Vink, J. M.

Abstract

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40–48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13–20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10−8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Published
2016

33. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Author

Stringer, S, primary, Minică, C C, additional, Verweij, K J H, additional, Mbarek, H, additional, Bernard, M, additional, Derringer, J, additional, van Eijk, K R, additional, Isen, J D, additional, Loukola, A, additional, Maciejewski, D F, additional, Mihailov, E, additional, van der Most, P J, additional, Sánchez-Mora, C, additional, Roos, L, additional, Sherva, R, additional, Walters, R, additional, Ware, J J, additional, Abdellaoui, A, additional, Bigdeli, T B, additional, Branje, S J T, additional, Brown, S A, additional, Bruinenberg, M, additional, Casas, M, additional, Esko, T, additional, Garcia-Martinez, I, additional, Gordon, S D, additional, Harris, J M, additional, Hartman, C A, additional, Henders, A K, additional, Heath, A C, additional, Hickie, I B, additional, Hickman, M, additional, Hopfer, C J, additional, Hottenga, J J, additional, Huizink, A C, additional, Irons, D E, additional, Kahn, R S, additional, Korhonen, T, additional, Kranzler, H R, additional, Krauter, K, additional, van Lier, P A C, additional, Lubke, G H, additional, Madden, P A F, additional, Mägi, R, additional, McGue, M K, additional, Medland, S E, additional, Meeus, W H J, additional, Miller, M B, additional, Montgomery, G W, additional, Nivard, M G, additional, Nolte, I M, additional, Oldehinkel, A J, additional, Pausova, Z, additional, Qaiser, B, additional, Quaye, L, additional, Ramos-Quiroga, J A, additional, Richarte, V, additional, Rose, R J, additional, Shin, J, additional, Stallings, M C, additional, Stiby, A I, additional, Wall, T L, additional, Wright, M J, additional, Koot, H M, additional, Paus, T, additional, Hewitt, J K, additional, Ribasés, M, additional, Kaprio, J, additional, Boks, M P, additional, Snieder, H, additional, Spector, T, additional, Munafò, M R, additional, Metspalu, A, additional, Gelernter, J, additional, Boomsma, D I, additional, Iacono, W G, additional, Martin, N G, additional, Gillespie, N A, additional, Derks, E M, additional, and Vink, J M, additional

Published
2016
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35. Adolescent Substance Use Groups: Antecedent and Concurrent Personality Differences in a Longitudinal Study

Author

Oliva, E. M., Keyes, M., Iacono, W. G., and McGue, M.

Subjects
mental disorders, behavior and behavior mechanisms
Abstract

This study attempted to extend Shedler and Block's () influential study, which found that adolescent drug experimenters had the healthiest personality functioning compared to abstainers and frequent users. Using a prospective design, we examined the relationship between antecedent and concurrent personality and age-18 substance use in a community sample of 1,298 twins (96% Caucasian, 49% male). Personality measures at ages 11 and 18 assessed positive emotionality (agentic and communal), negative emotionality, and constraint. Substance use groupsabstainers, experimenters, and problem userswere created at age 18. Age-18 substance use groups differed in age-11 and age-18 constraint such that problem users were lower than experimenters, who were lower than abstainers. Age-18 substance use groups did not differ in age-18 positive emotionality. However, abstainers were significantly lower than experimenters in communal positive emotionality, whereas female abstainers scored higher in agentic positive emotionality than female experimenters, who scored higher than female problem users. Experimenters were significantly lower in negative emotionality than problem users. Our findings are inconsistent with the notion that experimenters had the healthiest personality functioning and instead suggest different strengths and weaknesses for each group. Future studies should examine agentic and communal positive emotionality separately.

Published
2012
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36. Associations between substance use disorders and major depression in parents and late adolescent-emerging adult offspring: an adoption study

Author

Marmorstein, N. R., Iacono, W. G., and McGue, M.

Subjects
mental disorders
Abstract

Aims To examine whether major depressive disorder (MDD) and substance use disorders [SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)] in parents predicted increased risk for these disorders in late adolescentemerging adult offspring and, specifically, the extent to which the pattern of risk differed for adopted and non-adopted youth. Participants Late adolescent and emerging adult participants from the Sibling Interaction and Behavior Study (mean age?=?18.8), a community-based investigation of adopted and non-adopted adolescents, and their parents (adoptive parents of adopted youth, biological parents of non-adopted adolescents) were included. Measurements Structured interviews were used to assess these disorders. Findings (i) When the same disorder in parents and adolescents was examined, parental MDD was associated with increased risk for MDD among both adopted (P?

Published
2012
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39. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci.

Author

Liu, M., Malone, S. M., Vaidyanathan, U., Keller, M. C., Abecasis, G., Mcgue, M., Iacono, W. G., and Vrieze, S. I.

Subjects
GENETICS of schizophrenia, BRAIN, DISEASE susceptibility, ELECTROENCEPHALOGRAPHY, GENES, GENETIC polymorphisms, PSYCHOPHYSIOLOGY, PHENOTYPES, GENOTYPES
Abstract

BackgroundEndophenotypes are laboratory-based measures hypothesized to lie in the causal chain between genes and clinical disorder, and to serve as a more powerful way to identify genes associated with the disorder. One promise of endophenotypes is that they may assist in elucidating the neurobehavioral mechanisms by which an associated genetic polymorphism affects disorder risk in complex traits. We evaluated this promise by testing the extent to which variants discovered to be associated with schizophrenia through large-scale meta-analysis show associations with psychophysiological endophenotypes.MethodWe genome-wide genotyped and imputed 4905 individuals. Of these, 1837 were whole-genome-sequenced at 11× depth. In a community-based sample, we conducted targeted tests of variants within schizophrenia-associated loci, as well as genome-wide polygenic tests of association, with 17 psychophysiological endophenotypes including acoustic startle response and affective startle modulation, antisaccade, multiple frequencies of resting electroencephalogram (EEG), electrodermal activity and P300 event-related potential.ResultsUsing single variant tests and gene-based tests we found suggestive evidence for an association between contactin 4 (CNTN4) and antisaccade and P300. We were unable to find any other variant or gene within the 108 schizophrenia loci significantly associated with any of our 17 endophenotypes. Polygenic risk scores indexing genetic vulnerability to schizophrenia were not related to any of the psychophysiological endophenotypes after correction for multiple testing.ConclusionsThe results indicate significant difficulty in using psychophysiological endophenotypes to characterize the genetically influenced neurobehavioral mechanisms by which risk loci identified in genome-wide association studies affect disorder risk. [ABSTRACT FROM PUBLISHER]

Published
2017
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40. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, Boomsma, DI, van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, and Boomsma, DI

Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Published
2014

46. Gender differences and developmental change in externalizing disorders from late adolescence to early adulthood : A longitudinal twin study

Author

Hicks, B. M., Blonigen, D. M., Kramer, Mark, Krueger, R. F., Patrick, C. J., Iacono, W. G., McGue, M, Hicks, B. M., Blonigen, D. M., Kramer, Mark, Krueger, R. F., Patrick, C. J., Iacono, W. G., and McGue, M

Abstract

Using data from over 1,000 male and female twins participating in the Minnesota Twin Family Study, the authors examined developmental change, gender differences, and genetic and environmental contributions to the symptom levels of four externalizing disorders (adult antisocial behavior, alcohol dependence, nicotine dependence, and drug dependence) from ages 17 to 24. Both men and women increased in symptoms for each externalizing disorder, with men increasing at a greater rate than women, such that a modest gender gap at age 17 widened to a large one at age 24. Additionally, a mean-level gender difference on a latent Externalizing factor could account for the mean-level gender differences for the individual disorders. Biometric analyses revealed increasing genetic variation and heritability for men but a trend toward decreasing genetic variation and increasing environmental effects for women. Results illustrate the importance of gender and developmental context for symptom expression and the utility of structural models to integrate general trends and disorder-specific characteristics., United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) AA09367R01 AA009367 AA00175United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) R37 DA005147 R01 DA005147 DA05147United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) R21 MH065137-04 MH18869 MH65137 R21 MH065137 R21 MH065137-05 R21 MH065137-02 R21 MH065137-03 T32 MH018869 R21 MH065137-01

Published
2007
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48. Erratum: Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

Author

Vinkhuyzen, A A E, primary, Pedersen, N L, additional, Yang, J, additional, Lee, S H, additional, Magnusson, P K E, additional, Iacono, W G, additional, McGue, M, additional, Madden, P A F, additional, Heath, A C, additional, Luciano, M, additional, Payton, A, additional, Horan, M, additional, Ollier, W, additional, Pendleton, N, additional, Deary, I J, additional, Montgomery, G W, additional, Martin, N G, additional, Visscher, P M, additional, and Wray, N R, additional

Published
2012
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49. Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

Author

Vinkhuyzen, A A E, primary, Pedersen, N L, additional, Yang, J, additional, Lee, S H, additional, Magnusson, P K E, additional, Iacono, W G, additional, McGue, M, additional, Madden, P A F, additional, Heath, A C, additional, Luciano, M, additional, Payton, A, additional, Horan, M, additional, Ollier, W, additional, Pendleton, N, additional, Deary, I J, additional, Montgomery, G W, additional, Martin, N G, additional, Visscher, P M, additional, and Wray, N R, additional

Published
2012
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