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1. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, deJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA, Palotie, A, Hsieh, Y-C, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, and Chasman, DI

Subjects
Biological Psychology, Clinical and Health Psychology, Psychology, Genetics, Basic Behavioral and Social Science, Aging, Human Genome, Brain Disorders, Behavioral and Social Science, Mental Health, Neurosciences, Aged, Aged, 80 and over, Cell Adhesion Molecules, Cognition, Cohort Studies, Executive Function, Female, Genetic Association Studies, Genetic Variation, Genome-Wide Association Study, Genomics, Humans, Introns, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Single Nucleotide, White People, gamma-Aminobutyric Acid, Generation Scotland, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Published
2016

2. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

Author

Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, van der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Generation Scotland, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N, Knopman, DS, Kwok, JB, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, van Swieten, JC, Taylor, KD, Trollor, J, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, and Wright, AF

Subjects
Generation Scotland, Humans, Genetic Predisposition to Disease, HMGN1 Protein, Cohort Studies, Cognition, Cognition Disorders, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Scotland, Female, Male, Atherosclerosis, Genome-Wide Association Study, and over, Polymorphism, Single Nucleotide, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
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

4. Evaluation of the self-assessment knowledge regarding cardiopulmonary resuscitation in medical students at the University of Belgrade.

Author

MILENKOVIC, M., TESIC, M., HADZIBEGOVIC, A., PALIBRK, I., DJUKANOVIC, M., ROVIC, I., SIJAN, D., STANISAVLJEVIC, J., TVRTKOVIC, M., PETROVIC, K., JOVANOVIC, V., and STEVANOVIC, P.

Abstract

OBJECTIVE: Cardiopulmonary resuscitation (CPR) is a vital skill that can improve the outcome of patients with sudden cardiac arrest. To raise awareness about CPR some countries have introduced an obligatory First Aid Course (FAC), usually done parallelly to a driver's license (DL). While expected of doctors to know CPR, the curriculum of some medical schools does not seem to have enforced measures to improve that knowledge. The aim was to have students self-evaluate their current knowledge of CPR, comparing it before university and whether it improved during their studies. SUBJECTS AND METHODS: A cross-sectional study was conducted in October 2020 using an anonymous questionnaire among students at the Faculty of Medicine in Belgrade (studies in English). RESULTS: A total of 172 (66.7%) students possessed a DL, of which 39.8% felt they were ready, 45.8% felt neutral, and 14.4% felt unable to perform CPR. The total number of students that completed a FAC during their studies was 165. Analysis was performed on the ability assessment data after the first FAC during studies, comparing it to FAC for DL and assessments at the end of studies. No statistically significant difference was observed in the level of self-reported ability to perform CPR, while a statistically significant difference was found in ability assessments when comparing only the FAC for the DL, and the one after the first FAC during medical studies, with students feeling more prepared after the FAC for DL. Across the sample, 90.2% of the students wished they had more CPR training during their medical studies. CONCLUSIONS: From this study, it may conclude that students wish and need more CPR training in their curriculum. [ABSTRACT FROM AUTHOR]

Published
2023

5. Investigating the impact of London’s Ultra Low Emission Zone on children’s health: Children’s Health in London and Luton (CHILL): Protocol for a prospective parallel cohort study

Author

James Gauderman, Tsocheva I, Harpal Kalsi, Fletcher M, Ian Mudway, Chris Newby, Grainne Colligan, Frank J. Kelly, Crichlow C, Borislava Mihaylova, J Grigg, Louise Cross, Frances R. Balkwill, Sandra Eldridge, Scales J, Chris Griffiths, Petrovic K, Chavda J, Gurch Randhawa, Sean Beevers, Day B, Thomson A, Wood H, Keating M, John Wright, Keighley A, Tomini F, Aziz Sheikh, Dove R, Mon-Williams M, van Sluijs E, and Hall A

Subjects
education.field_of_study, medicine.medical_specialty, Public health, Population, Air pollution, Psychological intervention, medicine.disease_cause, Political science, Environmental health, Cohort, medicine, Life course approach, education, Air quality index, Cohort study
Abstract

IntroductionAir pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are therefore urgently needed not only to improve public health now, but to prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver clear health benefits is lacking. We established a natural experiment design study (CHILL: Children’s Health in London and Luton) to evaluate the impacts of the introduction of London’s Ultra Low Emission Zone (ULEZ) on children’s health.Methods and analysisCHILL is a prospective two-arm parallel longitudinal cohort study of children aged 6-9 years, attending primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site). The primary goal of the study is to examine the impact of changes in annual air pollutant exposures as oxides of nitrogen, nitrogen dioxide, particulate matter less than 2.5microns and 10microns (NOx, NO2, PM2.5, PM10 respectively) across the two sites on lung growth, measured as forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), over four consecutive years. Secondary outcomes being investigated include a range of respiratory health indicators as well as inequality and health economic measures.Ethics and disseminationEthics approval has been given by Queen Mary University of London Research Ethics Committee (ref 2018/08). Dissemination will target audiences through a variety of channels, including research papers, conference and media presentations, web summaries and social media. CHILL is funded by National Institute for Health Research (NIHR) Public Health Research (Ref 16/139/09) with additional funding by Natural Environment Research Council, NIHR CLAHRC North Thames, NIHR ARC North Thames, and the Mayor of London. ClinicalTrials.gov: NCT04695093Strengths and limitations of this studyStrengthsCHILL uses a prospective parallel cohort design, allowing robust conclusions to be drawn on the impact of the ULEZ - a major city-wide air quality mitigation strategy - on air quality and children’s respiratory health.CHILL study cohorts include children from large and ethnically diverse populations living in urban areas characterised by poor air quality.LimitationsAttrition of study cohort population over time, although this has been accounted for in the original design of the study.Potential diminution of the ULEZ air pollution signal due to pre-compliance with ULEZ restrictions in the run up to the introduction of the scheme in Central London on the 8th April 2019, and minor impacts of other pollution mitigation measures.Added complexity of accounting for effects of COVID-19 and related lockdowns on traffic flows, air quality and children’s health.

Published
2021
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12. Translating knowledge for legume-based farming for food and feed (Legumes Translated)

Author

Murphy-Bokern, D., Dauber, J., Rittler, L., Krön, Matthais, Schuler, J., Reckling, M., Willer, H., Haase, T., Schaumann, C., Lindstöm, K., Zimmer, C., Dewhurst, R., Barkas, D., Recknagel, J., Iancheva, A., Petrovic, K., Alves, S., O' Donovan, T., Orestis, R., and Watson, C.

Subjects
Crop rotation, Pea, Lupin, Bean, Agriculture, Biosiversity, Legumes, Soybean, European protein transition
Abstract

Legumes Translated is a new thematic network in Horizon 2020. It supports the Agricultural European Innovation Partnership (EIP Agri) by linking research- and practice-based knowledge to support legume cropping and use. It is therefore in line with the recently announced European Protein Plan (European Commission 2018) that mentions a knowledge platform for protein crops. The overall goal is to support the production and use of grain legume crops in Europe as part of an overall change in protein sourcing and use (Donau Soja, 2017). The challenges that legumes crops can help address are well-documented: the need for more diversity in cropping with more crops that support pollinators; yield stagnation in cereal-dominated systems (e.g. Brisson et al., 2010; Watson et al., 2017); and a 29% deficit in tradable plant protein that is met by about 35 million tonnes of soybean equivalent imported from the Americas (Murphy-Bokern et al., 2017). This is a fundamental challenge to the resilience, acceptance and performance of our agri-food systems. There are indications that Europe is now on the cusp of a significant change manifest in the positive political response to the Donau Soja European Soya Declaration and the European Commission’s work on Europe’s protein balance. Thematic networks are a key element of the EIP Agri. funded from Horizon 2020. They complement both operational groups and Horizon 2020 research and innovation projects by compiling and validating existing knowledge and best practices and providing wider access to this knowledge with particular emphasis on trans-national border knowledge interaction. Legumes Translated has three underlying principles: empowerment of innovators through understanding; practice- and research-based sources of knowledge are mutually supportive; and cropping and farming system innovation must go hand-in-hand with corresponding value chain developments (especially in livestock).

Published
2019
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13. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author

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

Published
2019

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

Author

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

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

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

Published
2019
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15. Guidance on estimation of abundance and density data of wild ruminant population: methods, challenges, possibilities

Author

Grignolio, S., Apollonio, Marco, Brivio, Francesca, Vicente, Joaquín, Acevedo, Pelayo, Palencia, Pablo, Petrovic, K., Keuling, Oliver, Grignolio, S., Apollonio, Marco, Brivio, Francesca, Vicente, Joaquín, Acevedo, Pelayo, Palencia, Pablo, Petrovic, K., and Keuling, Oliver

Abstract

The methods for estimating relative abundance and density in wild ruminant species are reviewed and insights on how to obtain reliable estimations by using those methods are provided. Eighteenmethods used in nineteenwild ruminant species widely distributed across Europe are reviewed. In accordance with the ENETWILD consortium objectives, we evaluate if different types of data can be used to generate harmonisedand comparable database at large scale and for calibration of hunting data into abundanceindices or population density. In addition, recommendations to select the methods to estimate the abundance or density and its implementations for ungulate populations are provided. How to increase the output quality provided by certain methods recognised as reliable (good accuracy and precision)and with the potential to be used for the validation and calibration ofother direct (i.e. based on observation of animals) or indirect (i.e. based on signs of animal activity) methods was recommended. Largely, the “counting” of large herbivores on a regional scale is often unfeasible, it can only be possible to accurately assess population status at local scale. We show that the habitat type plays a key role in the selection of the best method to determine density or relative abundance and that this is partially irrespective to species characteristics. A method that gives a density estimate rather than relative abundance, if possible, should be used. High‐quality hunting data statistics (collected at fine spatial resolution) have the highest availability and comparability potential across Europe, to give long‐term and large‐scale trends and should be used in predictive spatial modelling of wild ruminant relative abundance and density. Therefore, their standardized and harmonised collection is strongly recommended. On a local scale (e.g. management units), camera trapping is a method that can be conducted in different environmental conditions and at any time to collect robust data. I

Published
2020

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

Author

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

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

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

Published
2019

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

Author

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

Abstract

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

Published
2018
Full Text
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18. Genotypic and phenotypic resistance testing of HIV-1 in routine clinical care

Author

Hirsch, H., Drechsler, H., Holbro, A., Hamy, F., Sendi, P., Petrovic, K., Klimkait, T., and Battegay, M.

Subjects
food and beverages
Abstract

Data on genotypic and phenotypic resistance testing of HIV-1 in the routine clinical setting are lacking. In a retrospective single-center study, all patients (n=102) for whom genotypic resistance typing (GRT) and phenotypic resistance typing (PRT) were performed during the calendar year 2002 were examined. GRT and PRT results were concordant for 79% of the drugs, being highest for nevirapine (92%) and lowest for didanosine (57%). Concordance of results for protease inhibitors was lowest for lopinavir (78%) and highest for indinavir (88%). Discordant results for lamivudine were observed in 16% of patients; 90% of these results corresponded to high-level resistance by PRT and susceptibility by GRT. Overall, HIV loads were lower and CD4+ cell counts higher after therapy following resistance testing, but a significant association with the number of active drugs as predicted by GRT or PRT could not be identified. In a subgroup of 43 patients with virological failure under antiretroviral therapy and sufficient follow-up data, HIV loads were significantly lower after 3 and 6months. More patients with HIV loads

Published
2018

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

Author

Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. U and Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. U

Abstract

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

Published
2019

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

Author

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Trollor, Julian ; https://orcid.org/0000-0002-7685-2977, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Kochan, Nicole ; https://orcid.org/0000-0002-8630-6398, Lee, Teresa ; https://orcid.org/0000-0002-9734-6467, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, and Trollor, Julian ; https://orcid.org/0000-0002-7685-2977

Abstract

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

Published
2019

21. Science-based wildlife disease response

Author

Vicente, J., Apollonio, M., Blanco-Aguiar, J.A., Borowik, T., Brivio, F., Casaer, J., Croft, S., Ericsson, G., Ferroglio, E., Gavier-Widen, D., Gortázar, C., Jansen, P.A., Keuling, O., Kowalczyk, R., Petrovic, K., Plhal, R., Podgórski, T., Sange, M., Scandura, M., Schmidt, K., Smith, G.C., Soriguer, R., Thulke, Hans-Hermann, Zanet, S., Acevedo, P., Vicente, J., Apollonio, M., Blanco-Aguiar, J.A., Borowik, T., Brivio, F., Casaer, J., Croft, S., Ericsson, G., Ferroglio, E., Gavier-Widen, D., Gortázar, C., Jansen, P.A., Keuling, O., Kowalczyk, R., Petrovic, K., Plhal, R., Podgórski, T., Sange, M., Scandura, M., Schmidt, K., Smith, G.C., Soriguer, R., Thulke, Hans-Hermann, Zanet, S., and Acevedo, P.

Abstract

no abstract

Published
2019

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

Author

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

Abstract

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

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

Author

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

Abstract

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

Published
2018

26. Interventions to reduce the stigma of eating disorders: A systematic review and meta-analysis

Author

Doley, JR, Hart, LM, Stukas, AA, Petrovic, K, Bouguettaya, A, Paxton, SJ, Doley, JR, Hart, LM, Stukas, AA, Petrovic, K, Bouguettaya, A, and Paxton, SJ

Abstract

Stigma is a problem for individuals with eating disorders (EDs), forming a barrier to disclosure and help-seeking. Interventions to reduce ED stigma may help remove these barriers; however, it is not known which strategies (e.g., explaining etiology to reduce blame, contact with a person with an ED, or educating about ED) are effective in reducing stigma and related outcomes. This review described effectiveness of intervention strategies, and identified gaps in the literature. A search of four databases was performed using the terms (eating disorder* OR bulimi* OR anorexi* OR binge-eating disorder) AND (stigma* OR stereotyp* OR beliefs OR negative attitudes) AND (program OR experiment OR intervention OR education), with additional texts sought through LISTSERVs. Two raters screened papers, extracted data, and assessed quality. Stigma reduction strategies and study characteristics were examined in critical narrative synthesis. Exploratory meta-analysis compared the effects of biological and sociocultural explanations of EDs on attitudinal stigma. Eighteen papers were eligible for narrative synthesis, with four also eligible for inclusion in a meta-analysis. Biological explanations reduced stigma relative to other explanations, including sociocultural explanations in meta-analysis (g = .47, p < .001). Combined education and contact interventions improved stigma relative to control groups or over time. Most studies examined Anorexia Nervosa (AN) stigma and had mostly female, undergraduate participants. Despite apparent effectiveness, research should verify that biological explanations do not cause unintentional harm. Future research should evaluate in vivo contact, directly compare education and contact strategies, and aim to generalize findings across community populations.

Published
2017

27. Vitamin D and cognitive function:a Mendelian randomisation study

Author

Maddock, J. (Jane), Zhou, A. (Ang), Cavadino, A. (Alana), Kuźma, E. (Elżbieta), Bao, Y. (Yanchun), Smart, M. C. (Melissa C.), Saum, K.-U. (Kai-Uwe), Schöttker, B. (Ben), Engmann, J. (Jorgen), Kjærgaard, M. (Marie), Karhunen, V. (Ville), Zhan, Y. (Yiqiang), Lehtimäki, T. (Terho), Rovio, S. P. (Suvi P.), Byberg, L. (Liisa), Lahti, J. (Jari), Marques-Vidal, P. (Pedro), Sen, A. (Abhijit), Perna, L. (Laura), Schirmer, H. (Henrik), Singh-Manoux, A. (Archana), Auvinen, J. (Juha), Hutri-Kähönen, N. (Nina), Kähönen, M. (Mika), Kilander, L. (Lena), Räikkönen, K. (Katri), Melhus, H. (Håkan), Ingelsson, E. (Erik), Guessous, I. (Idris), Petrovic, K. E. (Katja E), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Vollenweider, P. (Peter), Lind, L. (Lars), Eriksson, J. G. (Johan G.), Michaëlsson, K. (Karl), Raitakari, O. T. (Olli T.), Hägg, S. (Sara), Pedersen, N. L. (Nancy L.), Herzig, K.-H. (Karl-Heinz), Järvelin, M.-R. (Marjo-Riitta), Veijola, J. (Juha), Kivimäki, M. (Mika), Jorde, R. (Rolf), Brenner, H. (Hermann), Kumari, M. (Meena), Power, C. (Chris), Llewellyn, D. J. (David J.), Hyppönen, E. (Elina), Maddock, J. (Jane), Zhou, A. (Ang), Cavadino, A. (Alana), Kuźma, E. (Elżbieta), Bao, Y. (Yanchun), Smart, M. C. (Melissa C.), Saum, K.-U. (Kai-Uwe), Schöttker, B. (Ben), Engmann, J. (Jorgen), Kjærgaard, M. (Marie), Karhunen, V. (Ville), Zhan, Y. (Yiqiang), Lehtimäki, T. (Terho), Rovio, S. P. (Suvi P.), Byberg, L. (Liisa), Lahti, J. (Jari), Marques-Vidal, P. (Pedro), Sen, A. (Abhijit), Perna, L. (Laura), Schirmer, H. (Henrik), Singh-Manoux, A. (Archana), Auvinen, J. (Juha), Hutri-Kähönen, N. (Nina), Kähönen, M. (Mika), Kilander, L. (Lena), Räikkönen, K. (Katri), Melhus, H. (Håkan), Ingelsson, E. (Erik), Guessous, I. (Idris), Petrovic, K. E. (Katja E), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Vollenweider, P. (Peter), Lind, L. (Lars), Eriksson, J. G. (Johan G.), Michaëlsson, K. (Karl), Raitakari, O. T. (Olli T.), Hägg, S. (Sara), Pedersen, N. L. (Nancy L.), Herzig, K.-H. (Karl-Heinz), Järvelin, M.-R. (Marjo-Riitta), Veijola, J. (Juha), Kivimäki, M. (Mika), Jorde, R. (Rolf), Brenner, H. (Hermann), Kumari, M. (Meena), Power, C. (Chris), Llewellyn, D. J. (David J.), and Hyppönen, E. (Elina)

Abstract

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

Published
2017

28. Rivastigmine in outpatient services: experience of 114 neurologists in Austria

Author

Petrovic K, Reinhold Schmidt, and Lechner A

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Phenylcarbamates, Rivastigmine, Neuropsychological Tests, Central nervous system disease, Cognition, Alzheimer Disease, Internal medicine, Outpatients, medicine, Humans, Pharmacology (medical), Dosing, Effects of sleep deprivation on cognitive performance, Adverse effect, Aged, Aged, 80 and over, Psychiatric Status Rating Scales, Chemotherapy, business.industry, medicine.disease, Surgery, Clinical trial, Psychiatry and Mental health, Neuroprotective Agents, Treatment Outcome, Austria, Disease Progression, Female, Carbamates, Alzheimer's disease, business, medicine.drug
Abstract

We performed an open-label study in Alzheimer patients on the use of rivastigmine in clinical routine. We evaluated the mode of dosing, safety and response to treatment over 24 weeks in 529 Alzheimer patients recruited by 114 neurologists. At the start of the study, and after 12 and 24 weeks, the participants were tested with the Mini-Mental State Examination and the Global Deterioration Scale. Titration of rivastigmine was slower than expected: After 2 weeks, only 41.8% of subjects received an effective daily dose of at least 6 mg. A total of 33.8% of patients experienced 305 mostly transient adverse events of mild or moderate intensity. Gastrointestinal symptoms occurred in 30.4% of subjects and symptoms of the nervous system in 16.4%. Similar to controlled trials, the cognitive performance of patients improved, with more than 60% of subjects showing improvement from baseline on the Mini-Mental State Examination by week 24. More than 40% of patients showed improvement on the Global Deterioration Scale. This study suggests that, in daily clinical practice, titration of rivastigmine deviates from the prescribing information. Under routine conditions, the safety profile of the drug is favourable, as is the response to treatment.

Published
2002
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29. Abstract OT1-01-06: PIQHASSO: Open label, non-randomized, multicenter phase 1/2b study investigating safety and efficacy of PQR309 and eribulin combination in patients (pts) with locally advanced (LA) or metastatic HER2 (-) and triple-negative breast cancer (TNBC) (study PQR309-007)

Author

López-Miranda, E, primary, Gávila, J, additional, Pernas, S, additional, Saura, C, additional, Oliveira, M, additional, Serra, V, additional, Schmid, P, additional, Lord, S, additional, Paez, D, additional, Perez, J, additional, Llombart, A, additional, Petrovic, K, additional, Dimitrijevic, S, additional, and Cortes, J, additional

Published
2017
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30. 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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31. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, C.A. (Carla), Bressler, J., Debette, S. (Stéphanie), Schuur, M. (Maaike), Smith, A.V. (Albert), Bis, J.C. (Joshua), Davies, G. (Gail), Trompet, S. (Stella), Smith, J.A., Björnsson, A. (Asgeir), Chibnik, L.B. (Lori), Liu, Y., Vitart, V. (Veronique), Kirin, M. (Mirna), Petrovic, K. (Katja), Polasek, O. (Ozren), Zgaga, L. (Lina), Fawns-Ritchie, C., Hoffmann, P. (Per), Karjalainen, J. (Juha), Lahti, J., Llewellyn, D.J., Schmidt, C.O. (Carsten O.), Mather, R., Chouraki, V. (Vincent), Sun, Q., Resnick, S.M. (Susan), Rose, L.M. (Lynda M.), Oldmeadow, C. (Christopher), Stewart, M., Smith, B.H., Gudnason, V. (Vilmundur), Yang, Q. (Qiong), Mirza, S.S. (Saira), Jukema, J.W., DeJager, P.L. (Philip L.), Harris, T.B. (Tamara), Liewald, D.C.M. (David), Amin, N. (Najaf), Coker, L.H. (Laura), Stegle, O. (Oliver), Lopez, O.L., Schmidt, R., Teumer, A. (Alexander), Ford, I., Karbalai, N. (Nazanin), Becker, J.T. (James), Jonsdottir, M.K. (Maria K.), Au, R., Fehrmann, R.S.N. (Rudolf), Herms, S. (Stefan), Nalls, M.A. (Michael), Zhao, W., Turner, S.T., Yaffe, K., Lohman, K. (Kurt), Swieten, J.C. (John) van, Kardia, S.L.R., Knopman, D.S. (David), Meeks, W.M. (William), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Schofield, P.W., Tanaka, T. (Toshiko), Stott, D.J. (David J.), Wang, J. (Jing), Ridker, P.M. (Paul), Gow, A.J., Pattie, A. (Alison), Starr, J.M. (John), Hocking, L.J., Armstrong, N.J. (Nicola), McLachlan, S. (Stela), Shulman, L. (Lee), Pilling, L.C. (Luke), Eiriksdottir, G. (Gudny), Scott, R.J., Kochan, N.A. (Nicole A.), Palotie, A., Hsieh, Y.-C. (Yi-Chen), Eriksson, J.G. (Johan G.), Penman, A.D. (Alan), Gottesman, R.F. (Rebecca), Oostra, B.A. (Ben), Yu, L., DeStefano, A.L. (Anita L.), Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A. (Albert), Slagboom, P.E. (Eline), Westendorp, R.G.J., Buckley, B.M. (Brendan M.), Wolf, P.A., Uitterlinden, A.G. (André), Psaty, B.M. (Bruce), Grabe, H.J. (Hans Jörgen), Bandinelli, S. (Stefania), Chasman, D.I. (Daniel), Grodstein, F. (Francine), Räikkönen, K. (Katri), Lambert, J.-C., Porteous, D.J. (David J.), Price, J.F. (Jackie F.), Sachdev, P.S. (Perminder), Ferrucci, L. (Luigi), Attia, J. (John), Rudan, I. (Igor), Hayward, C., Wright, A.F., Wilson, J.F. (James F), Cichon, S. (Sven), Franke, L. (Lude), Schmidt, H., Ding, J. (Jingzhong), Craen, A.J. (Anton) de, Fornage, M. (Myriam), Bennett, D.A. (David), Deary, I.J. (Ian), Ikram, M.A. (Arfan), Launer, L.J. (Lenore), Fitzpatrick, A.L., Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, Mosley, T.H. (Thomas H.), Ibrahim-Verbaas, C.A. (Carla), Bressler, J., Debette, S. (Stéphanie), Schuur, M. (Maaike), Smith, A.V. (Albert), Bis, J.C. (Joshua), Davies, G. (Gail), Trompet, S. (Stella), Smith, J.A., Björnsson, A. (Asgeir), Chibnik, L.B. (Lori), Liu, Y., Vitart, V. (Veronique), Kirin, M. (Mirna), Petrovic, K. (Katja), Polasek, O. (Ozren), Zgaga, L. (Lina), Fawns-Ritchie, C., Hoffmann, P. (Per), Karjalainen, J. (Juha), Lahti, J., Llewellyn, D.J., Schmidt, C.O. (Carsten O.), Mather, R., Chouraki, V. (Vincent), Sun, Q., Resnick, S.M. (Susan), Rose, L.M. (Lynda M.), Oldmeadow, C. (Christopher), Stewart, M., Smith, B.H., Gudnason, V. (Vilmundur), Yang, Q. (Qiong), Mirza, S.S. (Saira), Jukema, J.W., DeJager, P.L. (Philip L.), Harris, T.B. (Tamara), Liewald, D.C.M. (David), Amin, N. (Najaf), Coker, L.H. (Laura), Stegle, O. (Oliver), Lopez, O.L., Schmidt, R., Teumer, A. (Alexander), Ford, I., Karbalai, N. (Nazanin), Becker, J.T. (James), Jonsdottir, M.K. (Maria K.), Au, R., Fehrmann, R.S.N. (Rudolf), Herms, S. (Stefan), Nalls, M.A. (Michael), Zhao, W., Turner, S.T., Yaffe, K., Lohman, K. (Kurt), Swieten, J.C. (John) van, Kardia, S.L.R., Knopman, D.S. (David), Meeks, W.M. (William), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Schofield, P.W., Tanaka, T. (Toshiko), Stott, D.J. (David J.), Wang, J. (Jing), Ridker, P.M. (Paul), Gow, A.J., Pattie, A. (Alison), Starr, J.M. (John), Hocking, L.J., Armstrong, N.J. (Nicola), McLachlan, S. (Stela), Shulman, L. (Lee), Pilling, L.C. (Luke), Eiriksdottir, G. (Gudny), Scott, R.J., Kochan, N.A. (Nicole A.), Palotie, A., Hsieh, Y.-C. (Yi-Chen), Eriksson, J.G. (Johan G.), Penman, A.D. (Alan), Gottesman, R.F. (Rebecca), Oostra, B.A. (Ben), Yu, L., DeStefano, A.L. (Anita L.), Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A. (Albert), Slagboom, P.E. (Eline), Westendorp, R.G.J., Buckley, B.M. (Brendan M.), Wolf, P.A., Uitterlinden, A.G. (André), Psaty, B.M. (Bruce), Grabe, H.J. (Hans Jörgen), Bandinelli, S. (Stefania), Chasman, D.I. (Daniel), Grodstein, F. (Francine), Räikkönen, K. (Katri), Lambert, J.-C., Porteous, D.J. (David J.), Price, J.F. (Jackie F.), Sachdev, P.S. (Perminder), Ferrucci, L. (Luigi), Attia, J. (John), Rudan, I. (Igor), Hayward, C., Wright, A.F., Wilson, J.F. (James F), Cichon, S. (Sven), Franke, L. (Lude), Schmidt, H., Ding, J. (Jingzhong), Craen, A.J. (Anton) de, Fornage, M. (Myriam), Bennett, D.A. (David), Deary, I.J. (Ian), Ikram, M.A. (Arfan), Launer, L.J. (Lenore), Fitzpatrick, A.L., Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, and Mosley, T.H. (Thomas H.)

Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10 -8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10 -9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10 -4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10 -15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10 -11) and neuron cell-cell adhesion (P-value=1.48 × 10 -13).

Published
2016
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37. Psychosis following stab brain injury by a billiard stick

Author

Turkalj, I., Stojanovic, S., Petrovic, K., Njagulj, V., Ivan Mikov, and Spanovic, M.

Subjects
Original Article
Abstract

Traumatic brain injury sometimes can lead to psychotic disorder which resembles schizophrenia. We report a 17-year-old boy, admitted to psychiatric department for psychotic symptomatology. He had suffered penetrating craniocerebral injury after stabbing by a billiard stick, three years earlier. On admission, he expressed delusions with paranoid and religious content. The magnetic resonance imaging of the brain showed a 10 cm large tubular area of posttraumatic encephalomalacia of the left hemisphere, whereas the electroencephalography revealed slow left temporal activity. The patient's recovery was uneventful with clozapine at a dosage of 100 mg daily. This case shows the diagnostic challenge in differentiation between schizophrenia and psychotic disorder due to traumatic brain injury. The authors emphasise the importance of imaging of the brain, especially magnetic resonance, in establishing the diagnosis of psychotic disorder due to traumatic brain injury.

Published
2012

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

Author

Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., 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., Lundquist, Anders, Mather, K. A., Mirza, S. S., Nyberg, Lars, Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, Lars-Göran, 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., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley, Deary, I. J., Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., 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., Lundquist, Anders, Mather, K. A., Mirza, S. S., Nyberg, Lars, Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, Lars-Göran, 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., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley, and Deary, I. J.

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-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, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 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
Full Text
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40. 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, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, Van Der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Scotland, G, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N ; https://orcid.org/0000-0002-8630-6398, Knopman, DS, Kwok, JB ; https://orcid.org/0000-0001-9574-6195, Lambert, JC, Lee, T ; https://orcid.org/0000-0002-9734-6467, Li, G, Li, SC, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S ; https://orcid.org/0000-0003-4785-0224, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, Van Swieten, JC, Taylor, KD, Trollor, J ; https://orcid.org/0000-0002-7685-2977, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, Wright, AF, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, Schofield, Peter, Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, Van Der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Scotland, G, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N ; https://orcid.org/0000-0002-8630-6398, Knopman, DS, Kwok, JB ; https://orcid.org/0000-0001-9574-6195, Lambert, JC, Lee, T ; https://orcid.org/0000-0002-9734-6467, Li, G, Li, SC, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S ; https://orcid.org/0000-0003-4785-0224, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, Van Swieten, JC, Taylor, KD, Trollor, J ; https://orcid.org/0000-0002-7685-2977, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, Wright, AF, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, and Schofield, Peter

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

41. Genome-wide studies of verbal declarative memory in nondemented older people: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

Author

Debette, S. (Stéphanie), Ibrahim-Verbaas, C.A. (Carla), Bressler, J. (Jan), Schuur, M. (Maaike), Smith, A.V. (Davey), Bis, J.C. (Joshua), Davies, G. (Gail), Wolf, C. (Christiane), Gudnason, V. (Vilmundur), Chibnik, L.B. (Lori), Yang, Q. (Qiong Fang), DeStefano, A.L. (Anita), De Quervain, D.J.F. (Dominique J.F.), Srikanth, V. (Velandai), Lahti, J. (Jari), Grabe, H.J. (Hans Jörgen), Smith, J.A. (Jennifer A), Priebe, L., Yu, L. (Lei), Karbalai, N. (Nazanin), Hayward, C. (Caroline), Wilson, J.F. (James F), Campbell, H. (Harry), Petrovic, K. (Katja), Fornage, M. (Myriam), Chauhan, G. (Ganesh), Yeo, R. (Robin), Boxall, R. (Ruth), Becker, J.T. (James), Stegle, O. (Oliver), Mather, R., Chouraki, V. (Vincent), Sun, Q. (Qi), Rose, L.M. (Lynda), Resnick, S.M. (Susan), Oldmeadow, C. (Christopher), Kirin, M. (Mirna), Wright, A. (Alan), Jonsdottir, M.K. (Maria K.), Au, R. (Rhoda), Becker, A. (Albert), Amin, N. (Najaf), Nalls, M.A. (Michael), Turner, S.T. (Stephen), Kardia, S.L.R. (Sharon), Oostra, B.A. (Ben), Windham, G. (Gwen), Coker, L.H. (Laura), Zhao, W. (Wei), Knopman, D.S. (David), Heiss, G. (Gerardo), Griswold, M.D. (Michael), Gottesman, R.F. (Rebecca), Vitart, V. (Veronique), Hastie, N. (Nick), Zgaga, L. (Lina), Rudan, I. (Igor), Polasek, O. (Ozren), Holliday, E.G. (Elizabeth), Schofield, P. (Peter), Choi, S.-H. (Seung-Hoan), Tanaka, T. (Toshiko), An, Y. (Yang), Perry, R.T. (Rodney T.), Kennedy, R.E. (Richard E.), Sale, M.M. (Michèle M.), Wang, J. (Jing), Wadley, V.G. (Virginia G.), Liewald, D.C. (David C.), Ridker, P.M. (Paul), Gow, A.J. (Alan J.), Pattie, A. (Alison), Starr, J.M. (John), Porteous, D.J. (David J.), Liu, X. (Xuan), Thomson, R. (Russell), Armstrong, N.J. (Nicola), Eiriksdottir, G. (Gudny), Assareh, A.A. (Arezoo), Kochan, N.A. (Nicole A.), Widen, E. (Elisabeth), Palotie, A. (Aarno), Hsieh, Y.-C. (Yi-Chen), Eriksson, J.G. (Johan G.), Vogler, C. (Christian), Swieten, J.C. (John) van, Shulman, L. (Lee), Beiser, A. (Alexa), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten O.), Hoffmann, W. (Wolfgang), Nöthen, M.M. (Markus M.), Ferrucci, L. (Luigi), Attia, J. (John), Uitterlinden, A.G. (André), Amouyel, P. (Philippe), Dartigues, J.-F. (Jean-François), Amieva, H. (Hélène), Räikkönen, K. (Katri), Garcia, M. (Melissa), Wolf, P.A. (Philip), Hofman, A. (Albert), Longstreth Jr, W.T., Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), DeJager, P.L. (Philip L.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Breteler, M.M.B. (Monique), Teumer, A. (Alexander), Lopez, O.L. (Oscar), Cichon, S. (Sven), Chasman, D.I. (Daniel), Grodstein, F. (Francine), Müller-Myhsok, B. (B.), Tzourio, C. (Christophe), Papassotiropoulos, A. (Andreas), Bennett, D.A. (David), Ikram, M.A. (Arfan), Deary, I.J. (Ian), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Debette, S. (Stéphanie), Ibrahim-Verbaas, C.A. (Carla), Bressler, J. (Jan), Schuur, M. (Maaike), Smith, A.V. (Davey), Bis, J.C. (Joshua), Davies, G. (Gail), Wolf, C. (Christiane), Gudnason, V. (Vilmundur), Chibnik, L.B. (Lori), Yang, Q. (Qiong Fang), DeStefano, A.L. (Anita), De Quervain, D.J.F. (Dominique J.F.), Srikanth, V. (Velandai), Lahti, J. (Jari), Grabe, H.J. (Hans Jörgen), Smith, J.A. (Jennifer A), Priebe, L., Yu, L. (Lei), Karbalai, N. (Nazanin), Hayward, C. (Caroline), Wilson, J.F. (James F), Campbell, H. (Harry), Petrovic, K. (Katja), Fornage, M. (Myriam), Chauhan, G. (Ganesh), Yeo, R. (Robin), Boxall, R. (Ruth), Becker, J.T. (James), Stegle, O. (Oliver), Mather, R., Chouraki, V. (Vincent), Sun, Q. (Qi), Rose, L.M. (Lynda), Resnick, S.M. (Susan), Oldmeadow, C. (Christopher), Kirin, M. (Mirna), Wright, A. (Alan), Jonsdottir, M.K. (Maria K.), Au, R. (Rhoda), Becker, A. (Albert), Amin, N. (Najaf), Nalls, M.A. (Michael), Turner, S.T. (Stephen), Kardia, S.L.R. (Sharon), Oostra, B.A. (Ben), Windham, G. (Gwen), Coker, L.H. (Laura), Zhao, W. (Wei), Knopman, D.S. (David), Heiss, G. (Gerardo), Griswold, M.D. (Michael), Gottesman, R.F. (Rebecca), Vitart, V. (Veronique), Hastie, N. (Nick), Zgaga, L. (Lina), Rudan, I. (Igor), Polasek, O. (Ozren), Holliday, E.G. (Elizabeth), Schofield, P. (Peter), Choi, S.-H. (Seung-Hoan), Tanaka, T. (Toshiko), An, Y. (Yang), Perry, R.T. (Rodney T.), Kennedy, R.E. (Richard E.), Sale, M.M. (Michèle M.), Wang, J. (Jing), Wadley, V.G. (Virginia G.), Liewald, D.C. (David C.), Ridker, P.M. (Paul), Gow, A.J. (Alan J.), Pattie, A. (Alison), Starr, J.M. (John), Porteous, D.J. (David J.), Liu, X. (Xuan), Thomson, R. (Russell), Armstrong, N.J. (Nicola), Eiriksdottir, G. (Gudny), Assareh, A.A. (Arezoo), Kochan, N.A. (Nicole A.), Widen, E. (Elisabeth), Palotie, A. (Aarno), Hsieh, Y.-C. (Yi-Chen), Eriksson, J.G. (Johan G.), Vogler, C. (Christian), Swieten, J.C. (John) van, Shulman, L. (Lee), Beiser, A. (Alexa), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten O.), Hoffmann, W. (Wolfgang), Nöthen, M.M. (Markus M.), Ferrucci, L. (Luigi), Attia, J. (John), Uitterlinden, A.G. (André), Amouyel, P. (Philippe), Dartigues, J.-F. (Jean-François), Amieva, H. (Hélène), Räikkönen, K. (Katri), Garcia, M. (Melissa), Wolf, P.A. (Philip), Hofman, A. (Albert), Longstreth Jr, W.T., Psaty, B.M. (Bruce), Boerwinkle, E.A. (Eric), DeJager, P.L. (Philip L.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Breteler, M.M.B. (Monique), Teumer, A. (Alexander), Lopez, O.L. (Oscar), Cichon, S. (Sven), Chasman, D.I. (Daniel), Grodstein, F. (Francine), Müller-Myhsok, B. (B.), Tzourio, C. (Christophe), Papassotiropoulos, A. (Andreas), Bennett, D.A. (David), Ikram, M.A. (Arfan), Deary, I.J. (Ian), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), and Mosley, T.H. (Thomas H.)

Abstract

BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. MET

Published
2015
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42. Genome-wide studies of verbal declarative memory in nondemented older people: The cohorts for heart and aging research in genomic epidemiology consortium

Author

Debette, S., Ibrahim Verbaas, C.A., Bressler, J., Schuur, M., Smith, A., Bis, J.C., Davies, G., Wolf, C., Gudnason, V., Chibnik, L.B., Yang, Q., DeStefano, A.L., de Quervain, D.J.F., Srikanth, V., Lahti, J., Grabe, H.J., Smith, J.A., Priebe, L., Yu, L., Karbalai, N., Hayward, C., Wilson, J.F., Campbell, H., Petrovic, K., Fornage, M., Chauhan, G., Yeo, R., Boxall, R., Becker, J., Stegle, O., Mather, K.A., Chouraki, V., Sun, Q., Rose, L.M., Resnick, S., Oldmeadow, C., Kirin, M., Wright, A.F., Jonsdottir, M.K., Au, R., Becker, A., Amin, N., Nalls, M.A., Turner, S.T., Kardia, S.L.R., Oostra, B., Windham, G., Coker, L.H., Zhao, W., Knopman, D.S., Heiss, G., Griswold, M.E., Gottesman, R.F., Vitart, V., Hastie, N.D., Zgaga, L., Rudan, I., Polasek, O., Holliday, E.G., Schofield, P., Choi, S.H., Tanaka, T., An, Y., Perry, R.T., Kennedy, R.E., Sale, M.M., Wang, J., Wadley, V.G., Liewald, D.C., Ridker, P.M., Gow, A.J., Pattie, A., Starr, J.M., Porteous, D., Liu, X., Thomson, R., Armstrong, N.J., Eiriksdottir, G., Assareh, A.A., Kochan, N.A., Widen, E., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Vogler, C., van Swieten, J.C., Shulman, J.M., Beiser, A., Rotter, J., Schmidt, C.O., Hoffmann, W., Nöthen, M.M., Ferrucci, L., Attia, J., Uitterlinden, A.G., Amouyel, P., Dartigues, J-F, Amieva, H., Räikkönen, K., Garcia, M., Wolf, P.A., Hofman, A., Longstreth, W.T., Psaty, B.M., Boerwinkle, E., DeJager, P.L., Sachdev, P.S., Schmidt, R., Breteler, M.M.B., Teumer, A., Lopez, O.L., Cichon, S., Chasman, D.I., Grodstein, F., Müller-Myhsok, B., Tzourio, C., Papassotiropoulos, A., Bennett, D.A., Ikram, M.A., Deary, I.J., van Duijn, C.M., Launer, L., Fitzpatrick, A.L., Seshadri, S., Mosley, T.H., Debette, S., Ibrahim Verbaas, C.A., Bressler, J., Schuur, M., Smith, A., Bis, J.C., Davies, G., Wolf, C., Gudnason, V., Chibnik, L.B., Yang, Q., DeStefano, A.L., de Quervain, D.J.F., Srikanth, V., Lahti, J., Grabe, H.J., Smith, J.A., Priebe, L., Yu, L., Karbalai, N., Hayward, C., Wilson, J.F., Campbell, H., Petrovic, K., Fornage, M., Chauhan, G., Yeo, R., Boxall, R., Becker, J., Stegle, O., Mather, K.A., Chouraki, V., Sun, Q., Rose, L.M., Resnick, S., Oldmeadow, C., Kirin, M., Wright, A.F., Jonsdottir, M.K., Au, R., Becker, A., Amin, N., Nalls, M.A., Turner, S.T., Kardia, S.L.R., Oostra, B., Windham, G., Coker, L.H., Zhao, W., Knopman, D.S., Heiss, G., Griswold, M.E., Gottesman, R.F., Vitart, V., Hastie, N.D., Zgaga, L., Rudan, I., Polasek, O., Holliday, E.G., Schofield, P., Choi, S.H., Tanaka, T., An, Y., Perry, R.T., Kennedy, R.E., Sale, M.M., Wang, J., Wadley, V.G., Liewald, D.C., Ridker, P.M., Gow, A.J., Pattie, A., Starr, J.M., Porteous, D., Liu, X., Thomson, R., Armstrong, N.J., Eiriksdottir, G., Assareh, A.A., Kochan, N.A., Widen, E., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Vogler, C., van Swieten, J.C., Shulman, J.M., Beiser, A., Rotter, J., Schmidt, C.O., Hoffmann, W., Nöthen, M.M., Ferrucci, L., Attia, J., Uitterlinden, A.G., Amouyel, P., Dartigues, J-F, Amieva, H., Räikkönen, K., Garcia, M., Wolf, P.A., Hofman, A., Longstreth, W.T., Psaty, B.M., Boerwinkle, E., DeJager, P.L., Sachdev, P.S., Schmidt, R., Breteler, M.M.B., Teumer, A., Lopez, O.L., Cichon, S., Chasman, D.I., Grodstein, F., Müller-Myhsok, B., Tzourio, C., Papassotiropoulos, A., Bennett, D.A., Ikram, M.A., Deary, I.J., van Duijn, C.M., Launer, L., Fitzpatrick, A.L., Seshadri, S., and Mosley, T.H.

Abstract

Background Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. Methods We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10−6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. Results rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10−10) and replication cohorts (p = 5.65 × 10−8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10−8, and rs6813517 [SPOCK3], p = 2.58 × 10−8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. Conclusions This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

Published
2015

43. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, C.A., Bressler, J., Debette, S., Schuur, M., Smith, A.V., Bis, J.C., Davies, G., Trompet, S., Smith, J.A., Wolf, C., Chibnik, L.B., Liu, Y., Vitart, V., Kirin, M., Petrovic, K., Polasek, O., Zgaga, L., Fawns-Ritchie, C., Hoffmann, P., Karjalainen, J., Lahti, J., Llewellyn, D.J., Schmidt, C.O., Mather, K.A., Chouraki, V., Sun, Q., Resnick, S.M., Rose, L.M., Oldmeadow, C., Stewart, M., Smith, B.H., Gudnason, V., Yang, Q., Mirza, S.S., Jukema, J.W., deJager, P.L., Harris, T.B., Liewald, D.C., Amin, N., Coker, L.H., Stegle, O., Lopez, O.L., Schmidt, R., Teumer, A., Ford, I., Karbalai, N., Becker, J.T., Jonsdottir, M.K., Au, R., Fehrmann, R.S.N., Herms, S., Nalls, M., Zhao, W., Turner, S.T., Yaffe, K., Lohman, K., van Swieten, J.C., Kardia, S.L.R, Knopman, D.S., Meeks, W.M., Heiss, G., Holliday, E.G., Schofield, P.W., Tanaka, T., Stott, D.J., Wang, J., Ridker, P., Gow, A.J., Pattie, A, Starr, J.M., Hocking, L.J., Armstrong, N.J., McLachlan, S., Shulman, J.M., Pilling, L.C., Eiriksdottir, G., Scott, R.J., Kochan, N.A., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Penman, A., Gottesman, R.F., Oostra, B.A., Yu, L., DeStefano, A.L., Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A., Slagboom, P.E., Westendorp, R.G.J., Buckley, B.M., Wolf, P.A., Uitterlinden, A.G., Psaty, B.M., Grabe, H.J., Bandinelli, S., Chasman, D.I., Grodstein, F., Räikkönen, K., Lambert, J-C, Porteous, D.J., Price, J.F., Sachdev, P.S., Ferrucci, L., Attia, J.R., Rudan, I., Hayward, C., Wright, A.F., Wilson, J.F., Cichon, S., Franke, L., Schmidt, H., Ding, J., de Craen, A.J.M., Fornage, M., Bennett, D.A., Deary, I.J., Ikram, M.A., Launer, L.J., Fitzpatrick, A.L., Seshadri, S., van Duijn, C.M., Mosley, T.H., Ibrahim-Verbaas, C.A., Bressler, J., Debette, S., Schuur, M., Smith, A.V., Bis, J.C., Davies, G., Trompet, S., Smith, J.A., Wolf, C., Chibnik, L.B., Liu, Y., Vitart, V., Kirin, M., Petrovic, K., Polasek, O., Zgaga, L., Fawns-Ritchie, C., Hoffmann, P., Karjalainen, J., Lahti, J., Llewellyn, D.J., Schmidt, C.O., Mather, K.A., Chouraki, V., Sun, Q., Resnick, S.M., Rose, L.M., Oldmeadow, C., Stewart, M., Smith, B.H., Gudnason, V., Yang, Q., Mirza, S.S., Jukema, J.W., deJager, P.L., Harris, T.B., Liewald, D.C., Amin, N., Coker, L.H., Stegle, O., Lopez, O.L., Schmidt, R., Teumer, A., Ford, I., Karbalai, N., Becker, J.T., Jonsdottir, M.K., Au, R., Fehrmann, R.S.N., Herms, S., Nalls, M., Zhao, W., Turner, S.T., Yaffe, K., Lohman, K., van Swieten, J.C., Kardia, S.L.R, Knopman, D.S., Meeks, W.M., Heiss, G., Holliday, E.G., Schofield, P.W., Tanaka, T., Stott, D.J., Wang, J., Ridker, P., Gow, A.J., Pattie, A, Starr, J.M., Hocking, L.J., Armstrong, N.J., McLachlan, S., Shulman, J.M., Pilling, L.C., Eiriksdottir, G., Scott, R.J., Kochan, N.A., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Penman, A., Gottesman, R.F., Oostra, B.A., Yu, L., DeStefano, A.L., Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A., Slagboom, P.E., Westendorp, R.G.J., Buckley, B.M., Wolf, P.A., Uitterlinden, A.G., Psaty, B.M., Grabe, H.J., Bandinelli, S., Chasman, D.I., Grodstein, F., Räikkönen, K., Lambert, J-C, Porteous, D.J., Price, J.F., Sachdev, P.S., Ferrucci, L., Attia, J.R., Rudan, I., Hayward, C., Wright, A.F., Wilson, J.F., Cichon, S., Franke, L., Schmidt, H., Ding, J., de Craen, A.J.M., Fornage, M., Bennett, D.A., Deary, I.J., Ikram, M.A., Launer, L.J., Fitzpatrick, A.L., Seshadri, S., van Duijn, C.M., and Mosley, T.H.

Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10-8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10-9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10-4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10-15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10-11) and neuron cell-cell adhesion (P-value=1.48 × 10-13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.Molecular Psychiatry advance online publication, 14 April 2015; doi:10.1038/mp.2015.37.

Published
2015

44. Product Development Seminars - Key Factors for Successful Product Development in Student Teams

Author

Kreimeyer, Matthias, Braun, Stefanie, Baumberger, C., Meiwald, Thomas, Petrovic, K., Bernitz, M., and Stüber, N.

Subjects
teamwork, seminar, methodical design, success factors, design process, ddc
Abstract

This paper focuses on how to successfully run a cooperative student seminar on product development. The setup of a recent seminar is described in detail, showing important constraints and conditions. Two teams were monitored closely and examined in detail as to their different ways to proceed and how this contributes to the overall results. For means of evaluation, success factors for each step of the design process were determined with regard to the overall motivation. From this, recommendations for the supervision of following product development seminars are deduced.

Published
2005

50. The Molecular Genetic Architecture of Self-Employment

Author

Cherny, Stacey, van der Loos, MJHM, Rietveld, CA, Eklund, N, Koellinger, PD, Rivadeneira, F, Abecasis, GR, Ankra-Badu, GA, Baumeister, SE, Benjamin, DJ, Biffar, R, Blankenberg, S, Boomsma, DI, Cesarini, D, Cucca, F, de Geus, EJC, Dedoussis, G, Deloukas, P, Dimitriou, M, Eiriksdottir, G, Eriksson, J, Gieger, C, Gudnason, V, Höhne, B, Holle, R, Hottenga, JJ, Isaacs, A, Järvelin, MR, Johannesson, M, Kaakinen, M, Kähönen, M, Kanoni, S, Laaksonen, MA ; https://orcid.org/0000-0002-3676-0787, Lahti, J, Launer, LJ, Lehtimäki, T, Loitfelder, M, Magnusson, PKE, Naitza, S, Oostra, BA, Perola, M, Petrovic, K, Quaye, L, Raitakari, O, Ripatti, S, Scheet, P, Schlessinger, D, Schmidt, CO, Schmidt, H, Schmidt, R, Senft, A, Smith, AV, Spector, TD, Surakka, I, Svento, R, Terracciano, A, Tikkanen, E, van Duijn, CM, Viikari, J, Völzke, H, Wichmann, HE, Wild, PS, Willems, SM, Willemsen, G, van Rooij, FJA, Groenen, PJF, Uitterlinden, AG, Hofman, A, Thurik, AR, Cherny, Stacey, van der Loos, MJHM, Rietveld, CA, Eklund, N, Koellinger, PD, Rivadeneira, F, Abecasis, GR, Ankra-Badu, GA, Baumeister, SE, Benjamin, DJ, Biffar, R, Blankenberg, S, Boomsma, DI, Cesarini, D, Cucca, F, de Geus, EJC, Dedoussis, G, Deloukas, P, Dimitriou, M, Eiriksdottir, G, Eriksson, J, Gieger, C, Gudnason, V, Höhne, B, Holle, R, Hottenga, JJ, Isaacs, A, Järvelin, MR, Johannesson, M, Kaakinen, M, Kähönen, M, Kanoni, S, Laaksonen, MA ; https://orcid.org/0000-0002-3676-0787, Lahti, J, Launer, LJ, Lehtimäki, T, Loitfelder, M, Magnusson, PKE, Naitza, S, Oostra, BA, Perola, M, Petrovic, K, Quaye, L, Raitakari, O, Ripatti, S, Scheet, P, Schlessinger, D, Schmidt, CO, Schmidt, H, Schmidt, R, Senft, A, Smith, AV, Spector, TD, Surakka, I, Svento, R, Terracciano, A, Tikkanen, E, van Duijn, CM, Viikari, J, Völzke, H, Wichmann, HE, Wild, PS, Willems, SM, Willemsen, G, van Rooij, FJA, Groenen, PJF, Uitterlinden, AG, Hofman, A, and Thurik, AR

Published
2013

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