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1. Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

Author: Mathews, CA, de Leeuw, C, Goudriaan, A, Smit, AB, Yu, D, Scharf, J, Verheijen, MHG, and Posthuma, D
Subjects: gene‐set analysis, pathway analysis, GWAS, glia, Tourette syndrome
Abstract: Tourette Syndrome is a heritable neurodevelopmental disorder whose pathophysiology remainsunknown. Recent genomewide association studies suggest that it is a polygenic disorderinfluenced by many genes of small effect. We tested whether these genes cluster in cellularfunction by applying gene‐set analyses using expert curated sets of brain‐expressed genes in thecurrent largest available Tourette Syndrome genome‐wide association dataset, involving 1285cases and 4964 controls. The gene‐sets included specific synaptic, astrocytic, oliogodendrocyteand microglial functions. We report association of Tourette Syndrome with a set of genesinvolved in astrocyte function, specifically in astrocyte carbohydrate metabolism. Thisassociation is driven primarily by a subset of 33 genes involved in glycolysis and glutamatemetabolism through which astrocytes support synaptic function. Our results indicate for the firsttime that the process of astrocyte‐neuron metabolic coupling may be an important contributorto Tourette Syndrome pathogenesis.
Published: 2023

2. Degeneration of Species-Rich Calthion palustris Hay Meadows; Some Considerations on the Community Concept

Author: Grootjans, A. P., Fresco, L. F. M., de Leeuw, C. C., and Schipper, P. C.
Published: 1996

3. Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

Author: Mathews, CA, de Leeuw, C, Goudriaan, A, Smit, AB, Yu, D, Scharf, J, Verheijen, MHG, and Posthuma, D
Subjects: gene‐set analysis, pathway analysis, GWAS, glia, Tourette syndrome, gene‐set analysis, pathway analysis, GWAS, glia, Tourette syndrome
Abstract: Tourette Syndrome is a heritable neurodevelopmental disorder whose pathophysiology remainsunknown. Recent genomewide association studies suggest that it is a polygenic disorderinfluenced by many genes of small effect. We tested whether these genes cluster in cellularfunction by applying gene‐set analyses using expert curated sets of brain‐expressed genes in thecurrent largest available Tourette Syndrome genome‐wide association dataset, involving 1285cases and 4964 controls. The gene‐sets included specific synaptic, astrocytic, oliogodendrocyteand microglial functions. We report association of Tourette Syndrome with a set of genesinvolved in astrocyte function, specifically in astrocyte carbohydrate metabolism. Thisassociation is driven primarily by a subset of 33 genes involved in glycolysis and glutamatemetabolism through which astrocytes support synaptic function. Our results indicate for the firsttime that the process of astrocyte‐neuron metabolic coupling may be an important contributorto Tourette Syndrome pathogenesis.
Published: 2019

4. Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility

Author: van Blokland, I, Lanting, P, Ori, A, Vonk, J, Warmerdam, R, Herkert, J, Boulogne, F, Claringbould, A, Lopera-Maya, E, Bartels, M, Hottenga, J, Ganna, A, Karjalainen, J, Hayward, C, Fawns-Ritchie, C, Campbell, A, Porteous, D, Cirulli, E, Barrett, K, Riffle, S, Bolze, A, White, S, Tanudjaja, F, Wang, X, Ramirez, J, Lim, Y, Lu, J, Washington, N, de Geus, E, Deelen, P, Boezen, H, Franke, L, Mierau, J, Dekens, J, Nolte, I, Dijkema, M, Wiersma, H, Jankipersadsing, S, Cho, J, Loos, R, Moscati, A, Chang, Y, Choe, P, Chung, J, Ham, S, Joo, E, Jung, J, Kang, C, Kim, H, Kim, E, Lee, H, Park, S, Park, K, Park, J, Ryu, S, Song, K, Paik, N, Albillos, A, Asselta, R, Bujanda, L, Buti, M, Duga, S, Fernandez, J, Gomez, M, Invernizzi, P, Prati, D, Banales, J, Folseraas, T, Franke, A, Hov, J, Karlsen, T, Valenti, L, Degenhardt, F, Ellighaus, D, Eythorsson, E, Haraldsson, A, Helgason, D, Holm, H, Ingvarsson, R, Jonsdottir, I, Norddahl, G, Palsson, R, Saemundsdottir, J, Stefansson, K, Thorsteinsdottir, U, Gudbjartsson, D, Jonsson, H, Melsted, P, Sulem, P, Sveinbjornsson, G, Alarcon-Riquelme, M, Bernardo, D, Rello, S, Martinez-Bueno, M, Amtrano, S, Bruttini, M, Floriana, V, Giliberti, A, Benetti, E, Fallerini, C, Furini, S, Pinto, A, Baldassarri, M, Fava, F, Mari, F, Renieri, A, Croci, S, Tita, R, Frullanti, E, Altshul, D, Huang, Q, Hunt, K, Martin, H, Mason, D, Trembath, R, Trivedi, B, Wright, J, Finer, S, Griffiths, C, van Heel, D, Jannes, C, Krieger, J, Pereira, A, Marques, E, Dalton, K, Deboever, C, Jimenez-Morales, D, Palomera, A, Pinsky, B, Smith, E, Szalma, S, Tralau-Stewart, C, Wong, E, Gorzynski, J, de Jong, H, Amar, D, Delaneau, O, Hughes, C, Ioannidis, A, Raja, A, Rubinacci, S, Tanigawa, Y, Ashley, E, Bustamante, C, Parikh, V, Rivas, M, Wheeler, M, Busson, A, Goffard, J, Migeotte, I, Peyrassol, X, Smits, G, Vandernoot, I, Wilkin, F, Bouysran, Y, Pichon, B, Tiembe, N, Green, R, Karlson, B, Meigs, J, Mercader, J, Murphy, S, Perez, E, Slaugenhaupt, S, Smoller, J, Weiss, S, Woolley, A, Feng, Y, Nivard, M, Brusco, A, Bulik, C, Franchimont, D, Landen, M, Louis, E, Pedersen, N, Rahmouni, S, Striano, P, Vermeire, S, Zara, F, Al-Muftah, W, Badji, R, Ismail, S, Al-Sarraj, Y, Mbarek, H, Arumugam, P, Caulfield, M, Need, A, Oscroft, T, Rendon, A, Scott, R, Chan, G, Kousathanas, A, Moutsianas, L, Odhams, C, Pasko, D, Rhodes, D, Stuckey, A, Atkinson, E, Baya, N, Butler-Laporte, G, Finucane, H, Forgetta, V, Kanai, M, Karczewski, K, Koelling, N, Martin, A, Nakanishi, T, Palmer, D, Richards, J, Spencer, C, Turley, P, Walters, R, Wilson, D, Armstrong, J, O'Connell, A, Wyllie, D, Bryant, S, Churchhouse, C, Di Angelantonio, E, Chapman, M, Danesh, J, Ouwehand, W, Roberts, D, Watkins, N, Butterworth, A, Zhao, J, Biesecker, L, Davis, L, Kerchberger, E, Lee, S, Priest, J, Richards, B, Sankaran, V, Chwialkowska, K, Francescatto, M, Stevens, C, Trankiem, A, Balaconis, K, Liao, R, Daly, M, Neale, B, Bernasconi, A, Ceri, S, Cordioli, M, Niemi, M, Zhou, W, Nguyen, H, Solomonson, M, Gopalan, S, Hou, K, Jansen, P, de Leeuw, C, Lu, Z, Mancuso, N, Marouli, E, Papadopoulou, A, Pasaniuc, B, Pathak, G, Polimanti, R, Posthuma, D, Savage, J, Uffelmann, E, Visscher, P, Wendt, F, Wray, N, Yengo, L, van Blokland I. V., Lanting P., Ori A. P. S., Vonk J. M., Warmerdam R. C. A., Herkert J. C., Boulogne F., Claringbould A., Lopera-Maya E. A., Bartels M., Hottenga J. -J., Ganna A., Karjalainen J., Hayward C., Fawns-Ritchie C., Campbell A., Porteous D., Cirulli E. T., Barrett K. M. S., Riffle S., Bolze A., White S., Tanudjaja F., Wang X., Ramirez J. M., Lim Y. W., Lu J. T., Washington N. L., de Geus E. J. C., Deelen P., Boezen H. M., Franke L. H., Mierau J. O., Dekens J., Nolte I., Dijkema M. X. L., Wiersma H. H., Jankipersadsing S. A., Cho J. H., Loos R. J. F., Moscati A., Chang Y., Choe P. G., Chung J., Ham S., Joo E. -J., Jung J., Kang C. K., Kim H. -L., Kim H. B., Kim E. S., Lee H. -J., Park S., Park K. -U., Park J. S., Ryu S., Song K. -H., Kim H. -N., Paik N. -J., Albillos A., Asselta R., Bujanda L., Buti M., Duga S., Fernandez J., Gomez M. R., Invernizzi P., Prati D., Banales J. M., Folseraas T., Franke A., Hov J. R., Karlsen T. H., Valenti L., Degenhardt F., Ellighaus D., Eythorsson E. S., Haraldsson A., Helgason D., Holm H., Ingvarsson R. F., Jonsdottir I., Norddahl G. L., Palsson R., Saemundsdottir J., Stefansson K., Thorsteinsdottir U., Gudbjartsson D. F., Jonsson H., Melsted P., Sulem P., Sveinbjornsson G., Alarcon-Riquelme M. E., Bernardo D., Rello S. R., Martinez-Bueno M., Amtrano S., Bruttini M., Floriana V., Giliberti A. R., Benetti E., Fallerini C., Furini S., Pinto A. M., Baldassarri M., Fava F., Mari F., Renieri A., Croci S., Tita R., Frullanti E., Altshul D., Huang Q., Hunt K. A., Martin H. C., Mason D., Trembath R. C., Trivedi B., Wright J., Finer S., Griffiths C., van Heel D. A., Jannes C. E., Krieger J. E., Pereira A. C., Marques E., Dalton K., DeBoever C., Jimenez-Morales D., Palomera A. C., Pinsky B., Smith E., Szalma S., Tralau-Stewart C., Wong E., Gorzynski J., de Jong H., Amar D., Delaneau O., Hughes C., Ioannidis A., Raja A., Rubinacci S., Tanigawa Y., Ashley E., Bustamante C., Parikh V., Rivas M., Wheeler M., Busson A., Goffard J. -C., Migeotte I., Peyrassol X., Smits G., Vandernoot I., Wilkin F., Bouysran Y., Pichon B., Tiembe N., Green R., Karlson B., Meigs J., Mercader J., Murphy S., Perez E., Slaugenhaupt S., Smoller J., Weiss S., Woolley A., Feng Y. -C. A., Nivard M. G., Brusco A., Bulik C. M., Franchimont D., Landen M., Louis E., Pedersen N., Rahmouni S., Striano P., Vermeire S., Zara F., Al-Muftah W., Badji R., Ismail S., Al-Sarraj Y., Mbarek H., Arumugam P., Caulfield M., Need A. C., Oscroft T., Rendon A., Scott R. H., Chan G., Kousathanas A., Moutsianas L., Odhams C. A., Pasko D., Rhodes D., Stuckey A., Atkinson E. G., Baya N., Butler-Laporte G., Finucane H., Forgetta V., Kanai M., Karczewski K. J., Koelling N., Martin A. R., Nakanishi T., Palmer D. S., Richards J. B., Spencer C. C. A., Turley P., Walters R. K., Wilson D. J., Armstrong J., O'Connell A. M., Wyllie D. H., Bryant S., Churchhouse C., Di Angelantonio E., Chapman M., Danesh J., Ouwehand W., Roberts D., Watkins N., Butterworth A., Zhao J. H., Biesecker L., Davis L., van Heel D., Kerchberger E., Lee S., Priest J., Richards B., Sankaran V., Chwialkowska K., Francescatto M., Stevens C., Trankiem A., Balaconis K., Liao R., Daly M., Neale B., Bernasconi A., Ceri S., Cordioli M., Niemi M., Zhou W., Nguyen H., Solomonson M., Gopalan S., Hou K., Jansen P., de Leeuw C., Lu Z., Mancuso N., Marouli E., Papadopoulou A., Pasaniuc B., Pathak G., Polimanti R., Posthuma D., Savage J., Uffelmann E., Visscher P., Wendt F. R., Wray N., Yengo L., van Blokland, I, Lanting, P, Ori, A, Vonk, J, Warmerdam, R, Herkert, J, Boulogne, F, Claringbould, A, Lopera-Maya, E, Bartels, M, Hottenga, J, Ganna, A, Karjalainen, J, Hayward, C, Fawns-Ritchie, C, Campbell, A, Porteous, D, Cirulli, E, Barrett, K, Riffle, S, Bolze, A, White, S, Tanudjaja, F, Wang, X, Ramirez, J, Lim, Y, Lu, J, Washington, N, de Geus, E, Deelen, P, Boezen, H, Franke, L, Mierau, J, Dekens, J, Nolte, I, Dijkema, M, Wiersma, H, Jankipersadsing, S, Cho, J, Loos, R, Moscati, A, Chang, Y, Choe, P, Chung, J, Ham, S, Joo, E, Jung, J, Kang, C, Kim, H, Kim, E, Lee, H, Park, S, Park, K, Park, J, Ryu, S, Song, K, Paik, N, Albillos, A, Asselta, R, Bujanda, L, Buti, M, Duga, S, Fernandez, J, Gomez, M, Invernizzi, P, Prati, D, Banales, J, Folseraas, T, Franke, A, Hov, J, Karlsen, T, Valenti, L, Degenhardt, F, Ellighaus, D, Eythorsson, E, Haraldsson, A, Helgason, D, Holm, H, Ingvarsson, R, Jonsdottir, I, Norddahl, G, Palsson, R, Saemundsdottir, J, Stefansson, K, Thorsteinsdottir, U, Gudbjartsson, D, Jonsson, H, Melsted, P, Sulem, P, Sveinbjornsson, G, Alarcon-Riquelme, M, Bernardo, D, Rello, S, Martinez-Bueno, M, Amtrano, S, Bruttini, M, Floriana, V, Giliberti, A, Benetti, E, Fallerini, C, Furini, S, Pinto, A, Baldassarri, M, Fava, F, Mari, F, Renieri, A, Croci, S, Tita, R, Frullanti, E, Altshul, D, Huang, Q, Hunt, K, Martin, H, Mason, D, Trembath, R, Trivedi, B, Wright, J, Finer, S, Griffiths, C, van Heel, D, Jannes, C, Krieger, J, Pereira, A, Marques, E, Dalton, K, Deboever, C, Jimenez-Morales, D, Palomera, A, Pinsky, B, Smith, E, Szalma, S, Tralau-Stewart, C, Wong, E, Gorzynski, J, de Jong, H, Amar, D, Delaneau, O, Hughes, C, Ioannidis, A, Raja, A, Rubinacci, S, Tanigawa, Y, Ashley, E, Bustamante, C, Parikh, V, Rivas, M, Wheeler, M, Busson, A, Goffard, J, Migeotte, I, Peyrassol, X, Smits, G, Vandernoot, I, Wilkin, F, Bouysran, Y, Pichon, B, Tiembe, N, Green, R, Karlson, B, Meigs, J, Mercader, J, Murphy, S, Perez, E, Slaugenhaupt, S, Smoller, J, Weiss, S, Woolley, A, Feng, Y, Nivard, M, Brusco, A, Bulik, C, Franchimont, D, Landen, M, Louis, E, Pedersen, N, Rahmouni, S, Striano, P, Vermeire, S, Zara, F, Al-Muftah, W, Badji, R, Ismail, S, Al-Sarraj, Y, Mbarek, H, Arumugam, P, Caulfield, M, Need, A, Oscroft, T, Rendon, A, Scott, R, Chan, G, Kousathanas, A, Moutsianas, L, Odhams, C, Pasko, D, Rhodes, D, Stuckey, A, Atkinson, E, Baya, N, Butler-Laporte, G, Finucane, H, Forgetta, V, Kanai, M, Karczewski, K, Koelling, N, Martin, A, Nakanishi, T, Palmer, D, Richards, J, Spencer, C, Turley, P, Walters, R, Wilson, D, Armstrong, J, O'Connell, A, Wyllie, D, Bryant, S, Churchhouse, C, Di Angelantonio, E, Chapman, M, Danesh, J, Ouwehand, W, Roberts, D, Watkins, N, Butterworth, A, Zhao, J, Biesecker, L, Davis, L, Kerchberger, E, Lee, S, Priest, J, Richards, B, Sankaran, V, Chwialkowska, K, Francescatto, M, Stevens, C, Trankiem, A, Balaconis, K, Liao, R, Daly, M, Neale, B, Bernasconi, A, Ceri, S, Cordioli, M, Niemi, M, Zhou, W, Nguyen, H, Solomonson, M, Gopalan, S, Hou, K, Jansen, P, de Leeuw, C, Lu, Z, Mancuso, N, Marouli, E, Papadopoulou, A, Pasaniuc, B, Pathak, G, Polimanti, R, Posthuma, D, Savage, J, Uffelmann, E, Visscher, P, Wendt, F, Wray, N, Yengo, L, van Blokland I. V., Lanting P., Ori A. P. S., Vonk J. M., Warmerdam R. C. A., Herkert J. C., Boulogne F., Claringbould A., Lopera-Maya E. A., Bartels M., Hottenga J. -J., Ganna A., Karjalainen J., Hayward C., Fawns-Ritchie C., Campbell A., Porteous D., Cirulli E. T., Barrett K. M. S., Riffle S., Bolze A., White S., Tanudjaja F., Wang X., Ramirez J. M., Lim Y. W., Lu J. T., Washington N. L., de Geus E. J. C., Deelen P., Boezen H. M., Franke L. H., Mierau J. O., Dekens J., Nolte I., Dijkema M. X. L., Wiersma H. H., Jankipersadsing S. A., Cho J. H., Loos R. J. F., Moscati A., Chang Y., Choe P. G., Chung J., Ham S., Joo E. -J., Jung J., Kang C. K., Kim H. -L., Kim H. B., Kim E. S., Lee H. -J., Park S., Park K. -U., Park J. S., Ryu S., Song K. -H., Kim H. -N., Paik N. -J., Albillos A., Asselta R., Bujanda L., Buti M., Duga S., Fernandez J., Gomez M. R., Invernizzi P., Prati D., Banales J. M., Folseraas T., Franke A., Hov J. R., Karlsen T. H., Valenti L., Degenhardt F., Ellighaus D., Eythorsson E. S., Haraldsson A., Helgason D., Holm H., Ingvarsson R. F., Jonsdottir I., Norddahl G. L., Palsson R., Saemundsdottir J., Stefansson K., Thorsteinsdottir U., Gudbjartsson D. F., Jonsson H., Melsted P., Sulem P., Sveinbjornsson G., Alarcon-Riquelme M. E., Bernardo D., Rello S. R., Martinez-Bueno M., Amtrano S., Bruttini M., Floriana V., Giliberti A. R., Benetti E., Fallerini C., Furini S., Pinto A. M., Baldassarri M., Fava F., Mari F., Renieri A., Croci S., Tita R., Frullanti E., Altshul D., Huang Q., Hunt K. A., Martin H. C., Mason D., Trembath R. C., Trivedi B., Wright J., Finer S., Griffiths C., van Heel D. A., Jannes C. E., Krieger J. E., Pereira A. C., Marques E., Dalton K., DeBoever C., Jimenez-Morales D., Palomera A. C., Pinsky B., Smith E., Szalma S., Tralau-Stewart C., Wong E., Gorzynski J., de Jong H., Amar D., Delaneau O., Hughes C., Ioannidis A., Raja A., Rubinacci S., Tanigawa Y., Ashley E., Bustamante C., Parikh V., Rivas M., Wheeler M., Busson A., Goffard J. -C., Migeotte I., Peyrassol X., Smits G., Vandernoot I., Wilkin F., Bouysran Y., Pichon B., Tiembe N., Green R., Karlson B., Meigs J., Mercader J., Murphy S., Perez E., Slaugenhaupt S., Smoller J., Weiss S., Woolley A., Feng Y. -C. A., Nivard M. G., Brusco A., Bulik C. M., Franchimont D., Landen M., Louis E., Pedersen N., Rahmouni S., Striano P., Vermeire S., Zara F., Al-Muftah W., Badji R., Ismail S., Al-Sarraj Y., Mbarek H., Arumugam P., Caulfield M., Need A. C., Oscroft T., Rendon A., Scott R. H., Chan G., Kousathanas A., Moutsianas L., Odhams C. A., Pasko D., Rhodes D., Stuckey A., Atkinson E. G., Baya N., Butler-Laporte G., Finucane H., Forgetta V., Kanai M., Karczewski K. J., Koelling N., Martin A. R., Nakanishi T., Palmer D. S., Richards J. B., Spencer C. C. A., Turley P., Walters R. K., Wilson D. J., Armstrong J., O'Connell A. M., Wyllie D. H., Bryant S., Churchhouse C., Di Angelantonio E., Chapman M., Danesh J., Ouwehand W., Roberts D., Watkins N., Butterworth A., Zhao J. H., Biesecker L., Davis L., van Heel D., Kerchberger E., Lee S., Priest J., Richards B., Sankaran V., Chwialkowska K., Francescatto M., Stevens C., Trankiem A., Balaconis K., Liao R., Daly M., Neale B., Bernasconi A., Ceri S., Cordioli M., Niemi M., Zhou W., Nguyen H., Solomonson M., Gopalan S., Hou K., Jansen P., de Leeuw C., Lu Z., Mancuso N., Marouli E., Papadopoulou A., Pasaniuc B., Pathak G., Polimanti R., Posthuma D., Savage J., Uffelmann E., Visscher P., Wendt F. R., Wray N., and Yengo L.
Abstract: Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID- 19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, largeeffect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak.
Published: 2021

5. Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

Author: Mathews, CA, Mathews, CA, de Leeuw, C, Goudriaan, A, Smit, AB, Yu, D, Scharf, J, Verheijen, MHG, Posthuma, D, Mathews, CA, Mathews, CA, de Leeuw, C, Goudriaan, A, Smit, AB, Yu, D, Scharf, J, Verheijen, MHG, and Posthuma, D
Abstract: Tourette Syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genomewide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene‐set analyses using expert curated sets of brain‐expressed genes in the current largest available Tourette Syndrome genome‐wide association dataset, involving 1285 cases and 4964 controls. The gene‐sets included specific synaptic, astrocytic, oliogodendrocyte and microglial functions. We report association of Tourette Syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte‐neuron metabolic coupling may be an important contributor to Tourette Syndrome pathogenesis.
Published: 2022

6. What can genetic research teach us about the overlap and differences between psychiatric disorders?

Author: Peyrot, W. J., Nivard, M. G., de Leeuw, C. A., Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, and APH - Mental Health
Abstract: BACKGROUND: Genetic research has made continuous progress in the past years, as a results of the rapidly growing sample sizes and development of novel analytical tools. AIM: To present the latest developments in research into the genetic overlap and differences between psychiatric disorders. METHOD: Description of findings from recent literature. RESULTS: First of all, psychiatric disorders differ in their heritability, and consequently impact of environmental factors. Second, some disorders show high concordance in direction of genetic effects, while other disorders have rather different effects. Using these genetic (dis)similarities, subgroups of psychiatric disorders can also be defined. CONCLUSION: Genetic research is developing at rapid pace, and much more will be learned about the genetic overlap and differences between psychiatric disorders in the next years. The big promise -and challenge- will be to integrate genetic research with research of environmental factors, other biological measures and more detailed phenotypic information..
Published: 2022

7. The Information Approach to the Prediction of Interregional Trade Flows

Author: Uribe, Pedro, de Leeuw, C. G., and Theil, H.
Published: 1966

8. LAVA: An integrated framework for local genetic correlation analysis

Author: Werme, J., primary, van der Sluis, S., additional, Posthuma, D., additional, and de Leeuw, C. A., additional
Published: 2021
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9. CMT4J: Charcot–Marie–Tooth disorder caused by mutations in FIG4

Author: de Leeuw, C N
Published: 2008

10. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk

Author: Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., Sealock, J., Karlsson, Ida K., Hägg, S., Athanasiu, L., Voyle, N., Proitsi, P., Witoelar, A., Stringer, S., Aarsland, D., Almdahl, I. S., Andersen, F., Bergh, S., Bettella, F., Bjornsson, S., Brækhus, A., Bråthen, G., de Leeuw, C., Desikan, R. S., Djurovic, S., Dumitrescu, L., Fladby, T., Hohman, T. J., Jonsson, P. V., Kiddle, S. J., Rongve, A., Saltvedt, I., Sando, S. B., Selbæk, G., Shoai, M., Skene, N. G., Snaedal, J., Stordal, E., Ulstein, I. D., Wang, Y., White, L. R., Hardy, J., Hjerling-Leffler, J., Sullivan, P. F., van der Flier, W. M., Dobson, R., Davis, L. K., Stefansson, H., Stefansson, K., Pedersen, N. L., Ripke, S., Andreassen, O. A., Posthuma, D., Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., Sealock, J., Karlsson, Ida K., Hägg, S., Athanasiu, L., Voyle, N., Proitsi, P., Witoelar, A., Stringer, S., Aarsland, D., Almdahl, I. S., Andersen, F., Bergh, S., Bettella, F., Bjornsson, S., Brækhus, A., Bråthen, G., de Leeuw, C., Desikan, R. S., Djurovic, S., Dumitrescu, L., Fladby, T., Hohman, T. J., Jonsson, P. V., Kiddle, S. J., Rongve, A., Saltvedt, I., Sando, S. B., Selbæk, G., Shoai, M., Skene, N. G., Snaedal, J., Stordal, E., Ulstein, I. D., Wang, Y., White, L. R., Hardy, J., Hjerling-Leffler, J., Sullivan, P. F., van der Flier, W. M., Dobson, R., Davis, L. K., Stefansson, H., Stefansson, K., Pedersen, N. L., Ripke, S., Andreassen, O. A., and Posthuma, D.
Abstract: Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
Published: 2019
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11. Kansen voor Kwelders

Author: de Leeuw, C., Bakker, C., Baptist, M.J., and Elschot, Kelly
Subjects: Onderzoeksformatie, Ecosystemen, Life Science
Published: 2018

12. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author: Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., De Leeuw, C. A., Nagel, M., Awasthi, S., Barr, P. B., Coleman, J. R. I., Grasby, K. L., Hammerschlag, A. R., Kaminski, J. A., Karlsson, R., Krapohl, E., Lam, M., Nygaard, M., Reynolds, C. A., Trampush, J. W., Young, H., Zabaneh, D., Hägg, S., Hansell, N. K., Karlsson, Ida K., Linnarsson, S., Montgomery, G. W., Muñoz-Manchado, A. B., Quinlan, E. B., Schumann, G., Skene, N. G., Webb, B. T., White, T., Arking, D. E., Avramopoulos, D., Bilder, R. M., Bitsios, P., Burdick, K. E., Cannon, T. D., Chiba-Falek, O., Christoforou, A., Cirulli, E. T., Congdon, E., Corvin, A., Davies, G., Deary, I. J., Derosse, P., Dickinson, D., Djurovic, S., Donohoe, G., Conley, E. D., Eriksson, J. G., Espeseth, T., Freimer, N. A., Giakoumaki, S., Giegling, I., Gill, M., Glahn, D. C., Hariri, A. R., Hatzimanolis, A., Keller, M. C., Knowles, E., Koltai, D., Konte, B., Lahti, J., Le Hellard, S., Lencz, T., Liewald, D. C., London, E., Lundervold, A. J., Malhotra, A. K., Melle, I., Morris, D., Need, A. C., Ollier, W., Palotie, A., Payton, A., Pendleton, N., Poldrack, R. A., Räikkönen, K., Reinvang, I., Roussos, P., Rujescu, D., Sabb, F. W., Scult, M. A., Smeland, O. B., Smyrnis, N., Starr, J. M., Steen, V. M., Stefanis, N. C., Straub, R. E., Sundet, K., Tiemeier, H., Voineskos, A. N., Weinberger, D. R., Widen, E., Yu, J., Abecasis, G., Andreassen, O. A., Breen, G., Christiansen, L., Debrabant, B., Dick, D. M., Heinz, A., Hjerling-Leffler, J., Ikram, M. A., Kendler, K. S., Martin, N. G., Medland, S. E., Pedersen, N. L., Plomin, R., Polderman, T. J. C., Ripke, S., Van Der Sluis, S., Sullivan, P. F., Vrieze, S. I., Wright, M. J., Posthuma, D., Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., De Leeuw, C. A., Nagel, M., Awasthi, S., Barr, P. B., Coleman, J. R. I., Grasby, K. L., Hammerschlag, A. R., Kaminski, J. A., Karlsson, R., Krapohl, E., Lam, M., Nygaard, M., Reynolds, C. A., Trampush, J. W., Young, H., Zabaneh, D., Hägg, S., Hansell, N. K., Karlsson, Ida K., Linnarsson, S., Montgomery, G. W., Muñoz-Manchado, A. B., Quinlan, E. B., Schumann, G., Skene, N. G., Webb, B. T., White, T., Arking, D. E., Avramopoulos, D., Bilder, R. M., Bitsios, P., Burdick, K. E., Cannon, T. D., Chiba-Falek, O., Christoforou, A., Cirulli, E. T., Congdon, E., Corvin, A., Davies, G., Deary, I. J., Derosse, P., Dickinson, D., Djurovic, S., Donohoe, G., Conley, E. D., Eriksson, J. G., Espeseth, T., Freimer, N. A., Giakoumaki, S., Giegling, I., Gill, M., Glahn, D. C., Hariri, A. R., Hatzimanolis, A., Keller, M. C., Knowles, E., Koltai, D., Konte, B., Lahti, J., Le Hellard, S., Lencz, T., Liewald, D. C., London, E., Lundervold, A. J., Malhotra, A. K., Melle, I., Morris, D., Need, A. C., Ollier, W., Palotie, A., Payton, A., Pendleton, N., Poldrack, R. A., Räikkönen, K., Reinvang, I., Roussos, P., Rujescu, D., Sabb, F. W., Scult, M. A., Smeland, O. B., Smyrnis, N., Starr, J. M., Steen, V. M., Stefanis, N. C., Straub, R. E., Sundet, K., Tiemeier, H., Voineskos, A. N., Weinberger, D. R., Widen, E., Yu, J., Abecasis, G., Andreassen, O. A., Breen, G., Christiansen, L., Debrabant, B., Dick, D. M., Heinz, A., Hjerling-Leffler, J., Ikram, M. A., Kendler, K. S., Martin, N. G., Medland, S. E., Pedersen, N. L., Plomin, R., Polderman, T. J. C., Ripke, S., Van Der Sluis, S., Sullivan, P. F., Vrieze, S. I., Wright, M. J., and Posthuma, D.
Abstract: Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Published: 2018
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13. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method (vol 111, pg 13790, 2014)

Author: Rietveld, CA, Esko, T, Davies, G, Pers, TH, Turley, P, Benyamin, B, Chabris, CF, Emilsson, V, Johnson, AD, Lee, JJ, de Leeuw, C, Marioni, RE, Medland, SE, Miller, MB, Rostapshova, O, van der Lee, Sven, Vinkhuyzen, AAE, Amin, Najaf, Conley, D, Derringer, J, Duijn, Cornelia, Fehrmann, R, Franke, L, Glaeser, EL, Hansell, NK, Hayward, C, Iacono, WG, Ibrahim-Verbaas, C, Jaddoe, Vincent, Karjalainen, J, Laibson, D, Lichtenstein, P, Liewald, DC, Magnusson, PKE, Martin, NG, McGue, M, McMahon, G, Pedersen, NL, Pinker, S, Porteous, DJ, Posthuma, Daniëlle, Rivadeneira, Fernando, Smith, BH, Starr, JM, Tiemeier, Henning, Timpson, NJ, Trzaskowski, M, Uitterlinden, André, Verhulst, Frank, Ward, ME, Wright, MJ, Smith, GD, Deary, IJ, Johannesson, M, Plomin, R, Visscher, P, Benjamin, DJ, Cesarini, D, Koellinger, PD, Epidemiology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, Internal Medicine, and Psychiatry
Published: 2015

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

Author: Okbay, Aysu, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, Niels, Turley, P, Chen, GB, Emilsson, V, Meddens, SFW, Oskarsson, S, Pickrell, JK, Thom, K, Timshel, P, Vlaming, Ronald, Abdellaoui, A, Ahluwalia, TS, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Johan, Concas, MP, Derringer, J, Furlotte, NA, Galesloot, TE, Girotto, G, Gupta, R, Hall, LM, Harris, SE, Hofer, E, Horikoshi, M, Huffman, JE, Kaasik, K, Kalafati, IP, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sven, de Leeuw, C, Lind, PA, Lindgren, KO, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, van der Most, PJ, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, WJ, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, KE, Shi, JX, Smith, AV, Poot, Raymond, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N (Niek), Vuckovic, D, Wellmann, J, Westra, HJ, Yang, JY, Zhao, W, Zhu, ZH, Alizadeh, BZ, Amin, Najaf, Bakshi, A, Baumeister, SE, Biino, G, Bonnelykke, K, Boyle, PA, Campbell, H, Cappuccio, FP, Davies, G, De Neve, JE, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, DM, Faul, JD, Feitosa, MF, Forstner, AJ, Gandin, I, Gunnarsson, B, Halldorsson, BV, Harris, TB, Heath, AC, Hocking, LJ, Holliday, EG, Homuth, G, Horan, MA, Hottenga, JJ, De Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kahonen, M, Kanoni, S, Keltigangas-Jarvinen, L, Kiemeney, LALM, Kolcic, I, Koskinen, S, Kraja, AT, Kroh, M, Kutalik, Z, Latvala, A, Launer, LJ, Lebreton, MP, Levinson, DF, Lichtenstein, P, Lichtner, P, Liewald, DCM, Loukola, A, Madden, PA, Magi, R, Maki-Opas, T, Marioni, RE, Marques-Vidal, P, Meddens, GA, McMahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, GW, Myhre, R, Nelson, CP, Nyholt, DR, Ollier, WER, Palotie, A, Paternoster, L, Pedersen, NL, Petrovic, KE, Porteous, DJ, Raikkonen, K, Ring, SM, Robino, A, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, AR, Sarin, AP, Schmidt, Heléna, Scott, RJ, Smith, BH, Smith, JA, Staessen, JA, Steinhagen-Thiessen, E, Strauch, K, Terracciano, A, Tobin, MD, Ulivi, S, Vaccargiu, S, Quaye, L, van Rooij, FJA, Venturini, C, Vinkhuyzen, AAE, Volker, U, Volzke, H, Vonk, JM, Vozzi, D, Waage, J, Ware, EB, Willemsen, G, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Bisgaard, H, Boomsma, DI, Borecki, IB, Bultmann, U, Chabris, CF, Cucca, F, Cusi, D, Deary, IJ, Dedoussis, GV, Duijn, Cornelia, Eriksson, JG, Franke, B, Franke, L, Gasparini, P, Gejman, PV, Gieger, C, Grabe, HJ, Gratten, J, Groenen, Patrick, Gudnason, V, van der Harst, P, Hayward, C, Hinds, DA, Hoffmann, W, Hyppnen, E, Iacono, WG, Jacobsson, B, Jarvelin, MR, Jockel, KH, Kaprio, J, Kardia, SLR, Lehtimaki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Pendleton, N, Penninx, BWJH, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, Daniëlle, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sorensen, TIA, Spector, TD, Stefansson, K, Thorsteinsdottir, U, Thurik, Roy, Timpson, NJ, Tiemeier, Henning, Tung, JY, Uitterlinden, André, Vitart, V, Vollenweider, P, Weir, DR, Wilson, JF, Wright, AF, Conley, DC, Krueger, RF, Smith, GD, Hofman, Bert, Laibson, DI, Medland, SE, Meyer, MN, Yang, Jiaqi, Johannesson, M, Visscher, PM, Esko, T, Koellinger, PD, Cesarini, D, Benjamin, DJ, Okbay, Aysu, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, Niels, Turley, P, Chen, GB, Emilsson, V, Meddens, SFW, Oskarsson, S, Pickrell, JK, Thom, K, Timshel, P, Vlaming, Ronald, Abdellaoui, A, Ahluwalia, TS, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Johan, Concas, MP, Derringer, J, Furlotte, NA, Galesloot, TE, Girotto, G, Gupta, R, Hall, LM, Harris, SE, Hofer, E, Horikoshi, M, Huffman, JE, Kaasik, K, Kalafati, IP, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sven, de Leeuw, C, Lind, PA, Lindgren, KO, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, van der Most, PJ, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, WJ, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, KE, Shi, JX, Smith, AV, Poot, Raymond, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N (Niek), Vuckovic, D, Wellmann, J, Westra, HJ, Yang, JY, Zhao, W, Zhu, ZH, Alizadeh, BZ, Amin, Najaf, Bakshi, A, Baumeister, SE, Biino, G, Bonnelykke, K, Boyle, PA, Campbell, H, Cappuccio, FP, Davies, G, De Neve, JE, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, DM, Faul, JD, Feitosa, MF, Forstner, AJ, Gandin, I, Gunnarsson, B, Halldorsson, BV, Harris, TB, Heath, AC, Hocking, LJ, Holliday, EG, Homuth, G, Horan, MA, Hottenga, JJ, De Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kahonen, M, Kanoni, S, Keltigangas-Jarvinen, L, Kiemeney, LALM, Kolcic, I, Koskinen, S, Kraja, AT, Kroh, M, Kutalik, Z, Latvala, A, Launer, LJ, Lebreton, MP, Levinson, DF, Lichtenstein, P, Lichtner, P, Liewald, DCM, Loukola, A, Madden, PA, Magi, R, Maki-Opas, T, Marioni, RE, Marques-Vidal, P, Meddens, GA, McMahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, GW, Myhre, R, Nelson, CP, Nyholt, DR, Ollier, WER, Palotie, A, Paternoster, L, Pedersen, NL, Petrovic, KE, Porteous, DJ, Raikkonen, K, Ring, SM, Robino, A, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, AR, Sarin, AP, Schmidt, Heléna, Scott, RJ, Smith, BH, Smith, JA, Staessen, JA, Steinhagen-Thiessen, E, Strauch, K, Terracciano, A, Tobin, MD, Ulivi, S, Vaccargiu, S, Quaye, L, van Rooij, FJA, Venturini, C, Vinkhuyzen, AAE, Volker, U, Volzke, H, Vonk, JM, Vozzi, D, Waage, J, Ware, EB, Willemsen, G, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Bisgaard, H, Boomsma, DI, Borecki, IB, Bultmann, U, Chabris, CF, Cucca, F, Cusi, D, Deary, IJ, Dedoussis, GV, Duijn, Cornelia, Eriksson, JG, Franke, B, Franke, L, Gasparini, P, Gejman, PV, Gieger, C, Grabe, HJ, Gratten, J, Groenen, Patrick, Gudnason, V, van der Harst, P, Hayward, C, Hinds, DA, Hoffmann, W, Hyppnen, E, Iacono, WG, Jacobsson, B, Jarvelin, MR, Jockel, KH, Kaprio, J, Kardia, SLR, Lehtimaki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Pendleton, N, Penninx, BWJH, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, Daniëlle, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sorensen, TIA, Spector, TD, Stefansson, K, Thorsteinsdottir, U, Thurik, Roy, Timpson, NJ, Tiemeier, Henning, Tung, JY, Uitterlinden, André, Vitart, V, Vollenweider, P, Weir, DR, Wilson, JF, Wright, AF, Conley, DC, Krueger, RF, Smith, GD, Hofman, Bert, Laibson, DI, Medland, SE, Meyer, MN, Yang, Jiaqi, Johannesson, M, Visscher, PM, Esko, T, Koellinger, PD, Cesarini, D, and Benjamin, DJ
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(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) 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

15. Functional gene-set analysis does not support a major role for synaptic function in attention deficit/hyperactivity disorder

Author: Hammerschlag, AR, Polderman, TJC, de Leeuw, C, Tiemeier, Henning, White, Tonya, Smit, AB, Verhage, M, Posthuma, D, and Child and Adolescent Psychiatry / Psychology
Published: 2014

16. De Natuur van de Kust; tussen aangroei en afslag, 91 pp. Uitgave VBNE/uitgeverij Natuurmedia

Author: Lammerts, E.J., van Haperen, A., Arens, B., Grootjans, Albert, Kooijman, A., de Leeuw, C., Löffler, M., Nijssen, M, Slings, R., and Stuyfzand, P.J.
Published: 2014

17. Lock, Stock and Two Different Barrels: Comparing the Genetic Composition of Morphotypes of the Indo-Pacific Sponge Xestospongia testudinaria

Author: Swierts, T., Peijnenburg, K.T.C.A., de Leeuw, C., Cleary, D.F.R., Hörnlein, C., Setiawan, E., Wörheide, G., Erpenbeck, D., and de Voogd, N.J.
Abstract: The giant barrel sponge Xestospongia testudinaria is an ecologically important species that is widely distributed across the Indo-Pacific. Little is known, however, about the precise biogeographic distribution and the amount of morphological and genetic variation in this species. Here we provide the first detailed, fine-scaled (
Published: 2013

18. Über kompensatorische Hypertrophie und Hyperplasie des Lebergewebes beim Menschen

Author: de Leeuw, C.
Published: 1912
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19. Encephalitis epidemica und Grippeencephalitis

Author: Baumann, C. and de Leeuw, C. H.
Published: 1933
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20. Kasuistische Mitteilung über die konservative Behandlung zweier Fälle von Arachnoiditis spinalis circumscripta

Author: de Leeuw, C. H.
Published: 1935
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21. Augmenting Data With Published Results in Bayesian Linear Regression

Author: De Leeuw, C., Klugkist, I.G., Methodology and statistics for the behavioural and social sciences, Afd methoden en statistieken, Methodology and statistics for the behavioural and social sciences, and Afd methoden en statistieken
Subjects: Statistics and Probability, General linear model, Proper linear model, Computer science, Data Science, Linear model, Experimental and Cognitive Psychology, Regression analysis, General Medicine, Arts and Humanities (miscellaneous), Bayesian multivariate linear regression, Linear regression, Statistics, Bayesian linear regression, Regression diagnostic
Abstract: In most research, linear regression analyses are performed without taking into account published results (i.e., reported summary statistics) of similar previous studies. Although the prior density in Bayesian linear regression could accommodate such prior knowledge, formal models for doing so are absent from the literature. The goal of this article is therefore to develop a Bayesian model in which a linear regression analysis on current data is augmented with the reported regression coefficients (and standard errors) of previous studies. Two versions of this model are presented. The first version incorporates previous studies through the prior density and is applicable when the current and all previous studies are exchangeable. The second version models all studies in a hierarchical structure and is applicable when studies are not exchangeable. Both versions of the model are assessed using simulation studies. Performance for each in estimating the regression coefficients is consistently superior to using current data alone and is close to that of an equivalent model that uses the data from previous studies rather than reported regression coefficients. Overall the results show that augmenting data with results from previous studies is viable and yields significant improvements in the parameter estimation.
Published: 2012

22. Preadvies Duin- en Kustlandschap

Author: van den Burg, A., Arens, B., Esselink, Peter, de Leeuw, C., Kooijman, A.M, Stuyfzand, P., Grootjans, A.P., and Oost, A.P.
Published: 2009

23. Sturende processen op meso- en microschaal: natte duinen

Author: Grootjans, A.P., Stuijfzand, P.J., De Leeuw, C., and Hydrology and Geo-environmental sciences
Published: 2009

24. Preadvies duin- en kustlandschap

Author: Arens, S.M., van den Burg, A.B., Esselink, P., Grootjans, A.P., Jungerius, P.D., Kooijman, A.M., de Leeuw, C., Löffler, M., Nijssen, M., Oost, A.P., van Oosten, H.H., Stuyfzand, P.J., van Turnhout, C.A.M., Vogels, J.J., Wolters, M., and Paleoecology and Landscape Ecology (IBED, FNWI)
Published: 2009

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

Author: LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., Koellinger, P.D., LifeLines Cohort Study, Rietveld, C.A., Medland, S.E., Derringer, J., Yang, J., Esko, T., Martin, N.W., Westra, H.J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Amin, N., Barnard, J., Baumeister, S.E., Benke, K.S., Bielak, L.F., Boatman, J.A., Boyle, P.A., Davies, G., de Leeuw, C., Eklund, N., Evans, D.S., Ferhmann, R., Fischer, K., Gieger, C., Gjessing, H.K., Hägg, S., Harris, J.R., Hayward, C., Holzapfel, C., Ibrahim-Verbaas, C.A., Ingelsson, E., Jacobsson, B., Joshi, P.K., Jugessur, A., Kaakinen, M., Kanoni, S., Karjalainen, J., Kolcic, I., Kristiansson, K., Kutalik, Z., Lahti, J., Lee, S.H., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., McMahon, G., Vidal, P.M., Meirelles, O., Milani, L., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Petrovic, K.E., Peyrot, W.J., Polasek, O., Quaye, L., Reinmaa, E., Rice, J.P., Rizzi, T.S., Schmidt, H., Schmidt, R., Smith, A.V., Smith, J.A., Tanaka, T., Terracciano, A., van der Loos, M.J., Vitart, V., Völzke, H., Wellmann, J., Yu, L., Zhao, W., Allik, J., Attia, J.R., Bandinelli, S., Bastardot, F., Beauchamp, J., Bennett, D.A., Berger, K., Bierut, L.J., Boomsma, D.I., Bültmann, U., Campbell, H., Chabris, C.F., Cherkas, L., Chung, M.K., Cucca, F., de Andrade, M., De Jager, P.L., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Eiríksdóttir, G., Elderson, M.F., Eriksson, J.G., Evans, D.M., Faul, J.D., Ferrucci, L., Garcia, M.E., Grönberg, H., Guðnason, V., Hall, P., Harris, J.M., Harris, T.B., Hastie, N.D., Heath, A.C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Hottenga, J.J., Iacono, W.G., Illig, T., Järvelin, M.R., Kähönen, M., Kaprio, J., Kirkpatrick, R.M., Kowgier, M., Latvala, A., Launer, L.J., Lawlor, D.A., Lehtimäki, T., Li, J., Lichtenstein, P., Lichtner, P., Liewald, D.C., Madden, P.A., Magnusson, P.K., Mäkinen, T.E., Masala, M., McGue, M., Metspalu, A., Mielck, A., Miller, M.B., Montgomery, G.W., Mukherjee, S., Nyholt, D.R., Oostra, B.A., Palmer, L.J., Palotie, A., Penninx, B.W., Perola, M., Peyser, P.A., Preisig, M., Räikkönen, K., Raitakari, O.T., Realo, A., Ring, S.M., Ripatti, S., Rivadeneira, F., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Scott, R.J., Snieder, H., St Pourcain, B., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Teumer, A., Tiemeier, H., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Vollenweider, P., Vonk, J.M., Waeber, G., Weir, D.R., Wichmann, H.E., Widen, E., Willemsen, G., Wilson, J.F., Wright, A.F., Conley, D., Davey-Smith, G., Franke, L., Groenen, P.J., Johannesson, M., Kardia, S.L., Krueger, R.F., Laibson, D., Martin, N.G., Meyer, M.N., Posthuma, D., Thurik, A.R., Timpson, N.J., Uitterlinden, A.G., van Duijn, C.M., Visscher, P.M., Benjamin, D.J., Cesarini, D., and Koellinger, P.D.
Abstract: A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
Published: 2013

26. Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

Author: Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PKE, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O'Neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, DF, Gejman, PV, Laurent, C, Mowry, BJ, O'Donovan, MC, Pulver, AE, Schwab, SG, Wildenauer, DB, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, FB, Liang, K-Y, Maier, W, Mallet, J, Nertney, DA, Nestadt, G, Norton, N, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, Walsh, D, Williams, NM, Wormley, B, Psychosis Endophenotypes International Consortium, Arranz, MJ, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, RS, Kalaydjieva, L, Lawrie, S, Lewis, CM, Linszen, DH, Mata, I, McIntosh, A, Murray, RM, Ophoff, RA, Van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium 2, Donnelly, P, Barroso, I, Blackwell, JM, Brown, MA, Casas, JP, Corvin, AP, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, RD, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, MJ, Weston, P, Widaa, S, Whittaker, P, McCarthy, MI, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM, Sullivan, PF, Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PKE, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O'Neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, DF, Gejman, PV, Laurent, C, Mowry, BJ, O'Donovan, MC, Pulver, AE, Schwab, SG, Wildenauer, DB, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, FB, Liang, K-Y, Maier, W, Mallet, J, Nertney, DA, Nestadt, G, Norton, N, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, Walsh, D, Williams, NM, Wormley, B, Psychosis Endophenotypes International Consortium, Arranz, MJ, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, RS, Kalaydjieva, L, Lawrie, S, Lewis, CM, Linszen, DH, Mata, I, McIntosh, A, Murray, RM, Ophoff, RA, Van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium 2, Donnelly, P, Barroso, I, Blackwell, JM, Brown, MA, Casas, JP, Corvin, AP, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, RD, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, MJ, Weston, P, Widaa, S, Whittaker, P, McCarthy, MI, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM, and Sullivan, PF
Abstract: Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
Published: 2013

27. Replicated Evidence of Absence of Association between Serum S100B and (Risk of) Psychotic Disorder

Author: de Leeuw, C, Marcelis, M, Peeters, SCT, Verbeek, MM, Menheere, PPCA, den Haan, L (Lieuwe), van Os, J, Beveren, JM, de Leeuw, C, Marcelis, M, Peeters, SCT, Verbeek, MM, Menheere, PPCA, den Haan, L (Lieuwe), van Os, J, and Beveren, JM
Abstract: Background: S100B is a potential marker of neurological and psychiatric illness. In schizophrenia, increased S100B levels, as well as associations with acute positive and persisting negative symptoms, have been reported. It remains unclear whether S100B elevation, which possibly reflects glial dysfunction, is the consequence of disease or compensatory processes, or whether it is an indicator of familial risk. Methods: Serum samples were acquired from two large independent family samples (n = 348 and n = 254) in the Netherlands comprising patients with psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B was analyzed with a Liaison automated chemiluminescence system. Associations between familial risk of psychotic disorder and S100B were examined. Results: Results showed that S100B levels in patients (P) and siblings (S) were not significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI 20.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI 20.009 to 0.008, p = 0.926; and dataset 2: P vs. C: B = 0.008, 95% CI -0.011 to 0.028, p = 0.410; S vs. C: B = 0.002, 95% CI -0.016 to 0.021, p = 0.797). In patients, negative symptoms were positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in one of t Conclusions: S100B is neither an intermediate phenotype, nor a trait marker for psychotic illness.
Published: 2013

28. Augmenting data with published results in Bayesian linear regression

Author: Methodology and statistics for the behavioural and social sciences, Afd methoden en statistieken, De Leeuw, C., Klugkist, I.G., Methodology and statistics for the behavioural and social sciences, Afd methoden en statistieken, De Leeuw, C., and Klugkist, I.G.
Published: 2012

29. A regulatory toolbox of MiniPromoters to drive selective expression in the brain

Author: Portales-Casamar, E., Swanson, D., Liu, L., De Leeuw, C., Banks, K., Ho Sui, S., Fulton, D., Ali, J., Amirabbasi, M., Arenillas, D., Babyak, N., Black, S., Bonaguro, R., Brauer, E., Candido, T., Castellarin, M., Chen, J., Chen, Y., Cheng, J., Chopra, V., Docking, T., Dreolini, L., D'Souza, C., Flynn, E., Glenn, R., Hatakka, K., Hearty, T., Imanian, B., Jiang, S., Khorasan-zadeh, S., Komljenovic, I., Laprise, S., Liao, N., Lim, J., Lithwick, S., Liu, F., Liu, J., Lu, M., McConechy, M., McLeod, A., Milisavljevic, M., Mis, J., O'Connor, K., Palma, B., Palmquist, D., Schmouth, J., Swanson, M., Tam, B., Ticoll, A., Turner, J., Varhol, Richard, Vermeulen, J., Watkins, R., Wilson, G., Wong, B., Wong, S., Wong, T., Yang, G., Ypsilanti, A., Jones, S., Holt, R., Goldowitz, D., Wasserman, W., Simpson, E., Portales-Casamar, E., Swanson, D., Liu, L., De Leeuw, C., Banks, K., Ho Sui, S., Fulton, D., Ali, J., Amirabbasi, M., Arenillas, D., Babyak, N., Black, S., Bonaguro, R., Brauer, E., Candido, T., Castellarin, M., Chen, J., Chen, Y., Cheng, J., Chopra, V., Docking, T., Dreolini, L., D'Souza, C., Flynn, E., Glenn, R., Hatakka, K., Hearty, T., Imanian, B., Jiang, S., Khorasan-zadeh, S., Komljenovic, I., Laprise, S., Liao, N., Lim, J., Lithwick, S., Liu, F., Liu, J., Lu, M., McConechy, M., McLeod, A., Milisavljevic, M., Mis, J., O'Connor, K., Palma, B., Palmquist, D., Schmouth, J., Swanson, M., Tam, B., Ticoll, A., Turner, J., Varhol, Richard, Vermeulen, J., Watkins, R., Wilson, G., Wong, B., Wong, S., Wong, T., Yang, G., Ypsilanti, A., Jones, S., Holt, R., Goldowitz, D., Wasserman, W., and Simpson, E.
Abstract: The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or inmouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type - specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.
Published: 2010

30. Specific Glial Functions Contribute to Schizophrenia Susceptibility

Author: Goudriaan, A., primary, de Leeuw, C., additional, Ripke, S., additional, Hultman, C. M., additional, Sklar, P., additional, Sullivan, P. F., additional, Smit, A. B., additional, Posthuma, D., additional, and Verheijen, M. H. G., additional
Published: 2013
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31. Ecologische herstelmaatregelen in zoute wateren: Een ecologische evaluatie over de periode 1990-2000

Author: Esselink, P. (author), De Leeuw, C. (author), Graveland, J. (author), Berg, G. (author), Esselink, P. (author), De Leeuw, C. (author), Graveland, J. (author), and Berg, G. (author)
Abstract: DOEL Het rapport presenteert de resultaten van een evaluatie van 26 projecten van ecologisch herstel in of langs de zoute wateren. De projecten maken deel uit van het Programma Herstel en Inrichting, een uitvoeringsprogramma voortvloeiend uit de Derde Nota Waterhuishouding. Doel was om inzicht te verkrijgen in de succes- en faalfactoren van de projecten die in de eerste tien jaar van het programma zijn uitgevoerd om daar lering uit te trekken voor toekomstige herstelmaatregelen. OPZET De te evalueren projecten zijn geselecteerd aan de hand van drie criteria: Rijkswaterstaat (mede)financier, maatregelen uitgevoerd vóór 2000 en maatregelen uitgevoerd buitendijks of in verbinding met buitendijks, als overgang tussen binnendijks en buitendijks. Door middel van literatuuronderzoek, interviews en veldbezoeken zijn gegevens over de projecten verzameld. Het ging hierbij om algemene gegevens (oppervlak, beheerder, etc.), doelstelling, maatregelen, aard van de monitoring en de evaluatie. Bij de inventarisaties is gebruik gemaakt van een van te voren opgesteld evaluatieprotocol. Dat formulier is als checklist gebruikt tijdens de inventarisaties en interviews. De resultaten zijn verwerkt in een bespreking per project (Bijlage II). Projectoverstijgende punten zijn opgenomen in de hoofdtekst van het rapport. RESULTATEN De selectie leverde 26 herstelprojecten op: acht kwelders, vijf dynamisch kustbeheer (stuivende duinen, slufters), drie zoet-zoutovergangen, twee natuurlijke oevers, zes broedlocaties voor kustbroedvogels, een inlaag en een vispassage. Bij de inlaag, de vispassage en twee kwelderprojecten waren vogels het belangrijkste onderwerp (hoogwatervluchtplaats voor steltlopers en eenden, broedgebied voor kustbroedvogels). Er waren dus tien projecten met soortbescherming als hoofddoelstelling. Vier projecten hadden patroonbehoud en -herstel als hoofddoel (kwelders), vijf projecten waren te karakteriseren als procesherstel (Krekenproef, twee slufters en tweemaal dynamiekher
Published: 2003

32. Proefgebieden herstel zoet-zout overgangen in Noord Nederland: Een beschrijving van 18 projecten

Author: De Leeuw, C. (author), Meijer, M.L. (author), De Leeuw, C. (author), and Meijer, M.L. (author)
Abstract: In het kader van het project WONS*BRAK doet het Rijksinstituut voor Kust en Zee (RIKZ) langlopend onderzoek naar het herstel van estuariene gradienten (vaak zoet-zout overgangen genaamd) in het Nederlandse kustgebied. Als onderdeel van dit project is een studie naar de betekenis van kleinschalige proefgebieden voor het herstel van zoet-zout overgangen in Nederland uitgevoerd. Voor deze studie zijn in de periode van september tot december 2002 in totaal 33 projecten beschreven en geanalyseerd. Bureau Waardenburg heeft 15 projecten in het Deltagebied beschreven (S. Bouma, S.M. Veen & G.H. Bonhof, 2002). In dit rapport worden 18 projecten in het noorden van Nederland (Groningen, Friesland en Noord-Holland) samengevat. Voor het beschrijven van de proefprojecten is zoveel mogelijk dezelfde indeling en lay-out aangehouden. Per proefproject worden de volgende aspecten beschreven: 1. Kaart van het gebied (met begrenzing van de beheerseenheid en eventuele inrichtingsmaatregelen) 2. (Lucht)foto of inrichtingsschets van het gebied; 3. Samenvattende tabel met gegevens over locatie, oppervlakte, soort project, uitgangssituatie, doel (streefbeeld), inrichtings- en beheersmaatregelen, dimensies, periode van uitvoering en naam van de beherende instantie; 4. Historie van het gebied; 5. Probleem; 6. Doel / Streefbeeld; 7. Maatregelen; 8. Beheer; 9. Monitoring; 10. Resultaat; 11. Discussie; 12. Conclusie; 13. Aanbevelingen; 14. Contactpersonen; 15. Literatuur., WONS*BRAK
Published: 2003

33. Modelling the evolution of hydrocarbon systems in the inverted West Netherlands Basin, the Netherlands

Author: Van Balen, R.T, primary, Van Bergen, F, additional, De Leeuw, C, additional, Pagnier, H, additional, Simmelink, E, additional, Van Wees, J.-D, additional, and Verweij, H, additional
Published: 2000
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34. Modelling the hydrocarbon generation and migration in the West Netherlands Basin, the Netherlands

Author: van Balen, R.T., primary, van Bergen, F., additional, de Leeuw, C., additional, Pagnier, H., additional, Simmelink, H., additional, van Wees, J.D., additional, and Verweij, J.M., additional
Published: 2000
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35. Modelling Namurian Hydrocarbon Systems in the Dutch Part of the Southern North Sea Basin

Author: van Balen, R., primary, van Bergen, F., additional, de Leeuw, C., additional, and Pagnier, H., additional
Published: 2000
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36. Lung-Resistance–Related Protein Expression Is a Negative Predictive Factor for Response to Conventional Low but not to Intensified Dose Alkylating Chemotherapy in Multiple Myeloma

Author: Raaijmakers, H.G.P., primary, Izquierdo, M.A.I., additional, Lokhorst, H.M., additional, de Leeuw, C., additional, Belien, J.A.M., additional, Bloem, A.C., additional, Dekker, A.W., additional, Scheper, R.J., additional, and Sonneveld, P., additional
Published: 1998
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37. Transfusion of red cells after autologous bone marrow harvest in patients with acute leukemia and malignant lymphoma.

Author: Sonneveld, P., Leeuw, C.A., Schipperus, M., Lindemans, J., Abels, J., and de Leeuw, C A
Published: 1990
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38. THE INFORMATION APPROACH TO THE PREDICTION OF INTERREGIONAL TRADE FLOWS

Author: Uribe, Pedro, De Leeuw, C. G., and Theil, H.
Subjects: International Relations/Trade, Research Methods/ Statistical Methods
Published: 1965
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39. Sur quelques amines aromatiques secondaires en relation avec la di‐isopropylamine

Author: de Leeuw, C., primary
Published: 1911
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40. Genetic variants linked to education predict longevity

Author: Chris Power, Gail Davies, Ilaria Gandin, Panagiotis Deloukas, Jennifer E. Huffman, Pascal Timshel, Albert V. Smith, A. Kong, Paul Lichtenstein, Joseph K. Pickrell, Philipp Koellinger, P. L. De Jager, Reedik Mägi, G. B. Chen, Neil Pendleton, B. V. Halldórsson, George Dedoussis, Antti-Pekka Sarin, Natalia Pervjakova, Veikko Salomaa, Simona Vaccargiu, Ozren Polasek, K. H. Jöckel, Elisabeth Steinhagen-Thiessen, Y. Milaneschi, Jessica D. Faul, Patricia A. Boyle, Patrik K. E. Magnusson, Igor Rudan, Christopher P. Nelson, Vilmundur Gudnason, John Attia, Jürgen Wellmann, Kristi Läll, Konstantin Strauch, Stuart J. Ritchie, Markus Perola, Nicola Pirastu, Klaus Bønnelykke, Robert Karlsson, R. de Vlaming, Liisa Keltigangas-Jarvinen, Thomas Meitinger, Riccardo E. Marioni, Anu Loukola, Barbera Franke, Reinhold Schmidt, Maël Lebreton, Sven Oskarsson, E. Mihailov, Harm-Jan Westra, David R. Weir, Aldi T. Kraja, Niek Verweij, Peter M. Visscher, Hans-Jörgen Grabe, Johannes H. Brandsma, Mark Adams, R. J. Scott, G. Thorleifsson, Tõnu Esko, Mika Kähönen, Saskia P. Hagenaars, Patrick Turley, Johannes Waage, Peter Lichtner, Dragana Vuckovic, Antonietta Robino, Henry Völzke, Lydia Quaye, C. de Leeuw, Marika Kaakinen, Wei Zhao, Abdel Abdellaoui, Reka Nagy, Pedro Marques-Vidal, Johan G. Eriksson, Alan F. Wright, Andres Metspalu, Lavinia Paternoster, Momoko Horikoshi, Jan A. Staessen, Tarunveer S. Ahluwalia, Tian Liu, Martin Kroh, Aldo Rustichini, Giorgia Girotto, Cristina Venturini, Lili Milani, Jennifer A. Smith, Ginevra Biino, Tessel E. Galesloot, Michael A. Horan, Gerardus A. Meddens, James F. Wilson, Francesco Cucca, Peter Vollenweider, Erika Salvi, P. J. van der Most, Jari Lahti, Campbell A, David Laibson, Andrew Bakshi, Wolfgang Hoffmann, Tomi Mäki-Opas, Andreas J. Forstner, C M van Duijn, Nicholas G. Martin, Jonathan Marten, Ute Bültmann, Olli T. Raitakari, David A. Bennett, A.G. Uitterlinden, J. E. De Neve, Ingrid B. Borecki, WD Hill, Bo Jacobsson, Antti Latvala, Katri Räikkönen, Michael B. Miller, Jonathan P. Beauchamp, S. J. van der Lee, Ilja Demuth, Stavroula Kanoni, Veronique Vitart, Elina Hyppönen, N. Eklund, Francesco P. Cappuccio, Robert F. Krueger, Maria Pina Concas, Jaime Derringer, F. J.A. Van Rooij, Helena Schmidt, Patrick J. F. Groenen, Valur Emilsson, Rico Rueedi, Aysu Okbay, Georg Homuth, Edith Hofer, W. E. R. Ollier, Hannah Campbell, Paolo Gasparini, Mark Alan Fontana, Magnus Johannesson, Seppo Koskinen, Christopher F. Chabris, Jouke-Jan Hottenga, Christine Meisinger, Kari Stefansson, Jun Ding, Tia Sorensen, Brenda W.J.H. Penninx, Michelle N. Meyer, James J. Lee, Diego Vozzi, Gonneke Willemsen, K. Petrovic, Sarah E. Medland, Mary F. Feitosa, Henning Tiemeier, L. J. Launer, William G. Iacono, Massimo Mangino, Tune H. Pers, S. E. Baumeister, Christopher Oldmeadow, Grant W. Montgomery, Marjo-Riitta Järvelin, Jaakko Kaprio, Catharine R. Gale, S.F.W. Meddens, Kevin Thom, Klaus Berger, Pablo V. Gejman, Lude Franke, Gyda Bjornsdottir, Daniel J. Benjamin, Steven F. Lehrer, Krista Fischer, Alan R. Sanders, S. Ulivi, Katharina E. Schraut, Tim D. Spector, Amy Hofman, Matt McGue, Terho Lehtimäki, D. C. Liewald, Hans Bisgaard, L. Eisele, Astanand Jugessur, George Davey Smith, T.B. Harris, A.R. Thurik, Cornelius A. Rietveld, David Schlessinger, Z. Kutalik, David J. Porteous, Lynne J. Hocking, N J Timpson, A. Palotie, Lambertus A. Kiemeney, Ian J. Deary, Sharon L.R. Kardia, Peter K. Joshi, Nilesh J. Samani, Michael A. Province, Börge Schmidt, Richa Gupta, Carmen Amador, Erin B. Ware, Joyce Y. Tung, Ioanna-Panagiota Kalafati, Lars Bertram, Caroline Hayward, P. van der Harst, Penelope A. Lind, Kadri Kaasik, N.A. Furlotte, Sarah E. Harris, B. St Pourcain, Susan M. Ring, Zhihong Zhu, Alexander Teumer, Behrooz Z. Alizadeh, Judith M. Vonk, Blair H. Smith, A Payton, Wouter J. Peyrot, Jacob Gratten, Douglas F. Levinson, C Gieger, Leanne M. Hall, Andrew Heath, Mario Pirastu, Peter Eibich, Nancy L. Pedersen, Ronny Myhre, Antonio Terracciano, David M. Evans, Raymond A. Poot, Uwe Völker, Dorret I. Boomsma, Clemens Baumbach, Unnur Thorsteinsdottir, Ivana Kolcic, Jia-Shu Yang, Dalton Conley, A. A. Vinkhuyzen, Danielle Posthuma, Karl-Oskar Lindgren, Olga Rostapshova, Jonas Bacelis, Daniele Cusi, Yong Qian, Bjarni Gunnarsson, George McMahon, Elizabeth G. Holliday, Pamela A. F. Madden, David A. Hinds, David Cesarini, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Applied Economics, Epidemiology, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Aletta Jacobs School of Public Health, Public Health Research (PHR), Stem Cell Aging Leukemia and Lymphoma (SALL), Cardiovascular Centre (CVC), Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, EMGO - Mental health, Complex Trait Genetics, Biological Psychology, Marioni, RE, Ritchie, SJ, Joshi, PK, Hagenaars, SP, Hypponen, E, Benjamin, DJ, Social Science Genetic Association Consortium, Marioni, Re, Ritchie, Sj, Joshi, Pk, Hagenaars, Sp, Okbay, A, Fischer, K, Adams, Mj, Hill, Wd, Davies, G, Nagy, R, Amador, C, Läll, K, Metspalu, A, Liewald, Dc, Campbell, A, Wilson, Jf, Hayward, C, Esko, T, Porteous, Dj, Gale, Cr, Deary, Ij, Beauchamp, Jp, Fontana, Ma, Lee, Jj, Pers, Th, Rietveld, Ca, Turley, P, Chen, Gb, Emilsson, V, Meddens, Sf, Oskarsson, S, Pickrell, Jk, Thom, K, Timshel, P, de Vlaming, R, Abdellaoui, A, Ahluwalia, T, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Jh, Concas, MARIA PINA, Derringer, J, Furlotte, Na, Galesloot, Te, Girotto, Giorgia, Gupta, R, Hall, Lm, Harris, Se, Hofer, E, Horikoshi, M, Huffman, Je, Kaasik, K, Kalafati, Ip, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sj, de Leeuw, C, Lind, Pa, Lindgren, Ko, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, Mb, van der Most, Pj, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, Wj, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, Ke, Shi, J, Smith, Av, Poot, Ra, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N, Vuckovic, Dragana, Wellmann, J, Westra, Hj, Yang, J, Zhao, W, Zhu, Z, Alizadeh, Bz, Amin, N, Bakshi, A, Baumeister, Se, Biino, G, Bønnelykke, K, Boyle, Pa, Campbell, H, Cappuccio, Fp, De Neve, Je, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, Dm, Faul, Jd, Feitosa, Mf, Forstner, Aj, Gandin, Ilaria, Gunnarsson, B, Halldórsson, Bv, Harris, Tb, Heath, Ac, Hocking, Lj, Holliday, Eg, Homuth, G, Horan, Ma, Hottenga, Jj, de Jager, Pl, Jugessur, A, Kaakinen, Ma, Kähönen, M, Kanoni, S, Keltigangas Järvinen, L, Kiemeney, La, Kolcic, I, Koskinen, S, Kraja, At, Kroh, M, Kutalik, Z, Latvala, A, Launer, Lj, Lebreton, Mp, Levinson, Df, Lichtenstein, P, Lichtner, P, Loukola, A, Madden, Pa, Mägi, R, Mäki Opas, T, Marques Vidal, P, Meddens, Ga, Mcmahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, Gw, Myhre, R, Nelson, Cp, Nyholt, Dr, Ollier, We, Palotie, A, Paternoster, L, Pedersen, Nl, Petrovic, Ke, Räikkönen, K, Ring, Sm, Robino, Antonietta, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, Ar, Sarin, Ap, Schmidt, H, Scott, Rj, Smith, Bh, Smith, Ja, Staessen, Ja, Steinhagen Thiessen, E, Strauch, K, Terracciano, A, Tobin, Md, Ulivi, Sheila, Vaccargiu, S, Quaye, L, van Rooij, Fj, Venturini, C, Vinkhuyzen, Aa, Völker, U, Völzke, H, Vonk, Jm, Vozzi, Diego, Waage, J, Ware, Eb, Willemsen, G, Attia, Jr, Bennett, Da, Berger, K, Bertram, L, Bisgaard, H, Boomsma, Di, Borecki, Ib, Bultmann, U, Chabris, Cf, Cucca, F, Cusi, D, Dedoussis, Gv, van Duijn, Cm, Eriksson, Jg, Franke, B, Franke, L, Gasparini, Paolo, Gejman, Pv, Gieger, C, Grabe, Hj, Gratten, J, Groenen, Pj, Gudnason, V, van der Harst, P, Hinds, Da, Hoffmann, W, Iacono, Wg, Jacobsson, B, Järvelin, Mr, Jöckel, Kh, Kaprio, J, Kardia, Sl, Lehtimäki, T, Lehrer, Sf, Magnusson, Pk, Martin, Ng, Mcgue, M, Pendleton, N, Penninx, Bw, Perola, M, Pirastu, Nicola, Pirastu, M, Polasek, O, Posthuma, D, Power, C, Province, Ma, Samani, Nj, Schlessinger, D, Schmidt, R, Sørensen, Ti, Spector, Td, Stefansson, K, Thorsteinsdottir, U, Thurik, Ar, Timpson, Nj, Tiemeier, H, Tung, Jy, Uitterlinden, Ag, Vitart, V, Vollenweider, P, Weir, Dr, Wright, Af, Conley, Dc, Krueger, Rf, Smith, Gd, Hofman, A, Laibson, Di, Medland, Se, Meyer, Mn, Johannesson, M, Visscher, Pm, Koellinger, Pd, Cesarini, D, and Benjamin, Dj
Subjects: Netherlands Twin Register (NTR), 0301 basic medicine, Male, Parents, education: longevity: prediction: polygenic score [genetics], Multifactorial Inheritance, polygenic, Lebenserwartung, Cohort Studies, 0302 clinical medicine, Databases, Genetic, Medicine, genetics, polygenic score, longevity, education, gene, Soziales und Gesundheit, media_common, Aged, 80 and over, education, Multidisciplinary, Longevity, Middle Aged, Biobank, humanities, 3. Good health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, Educational Status, Female, Cohort study, Estonia, education, longevity, polygenic, Offspring, media_common.quotation_subject, Kultursektor, Prognose, Lernen, Lower risk, Education, 03 medical and health sciences, longevity, SDG 3 - Good Health and Well-being, Commentaries, Polygenic score, Journal Article, Genetics, Humans, Non-Profit-Sektor, Genetic Association Studies, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, ta1184, Genetic Variation, prediction, Educational attainment, United Kingdom, Gesundheitsstatistik, 030104 developmental biology, Genetic epidemiology, Scotland, Gesundheitszustand, Genetische Forschung, business, Prediction, Bildung, 030217 neurology & neurosurgery, Demography
Abstract: Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total n deaths = 79,702) and ∼2.4% lower risk for fathers (total n deaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity. Marioni RE, Ritchie SJ, Joshi PK, Hagenaars SP, Okbay A, Fischer K, Adams MJ, Hill WD, Davies G, Social Science Genetic Association Consortium, Nagy R, Amador C, Läll K, Metspalu A, Liewald DC, Campbell A, Wilson JF, Hayward C, Esko T, Porteous DJ, Proceedings of the National Academy of Sciences of the United States of America, 2016, vol. 113, no. 47, pp. 13366-13371, 2016 Refereed/Peer-reviewed
Published: 2016
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41. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

Author: Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.
Subjects: Netherlands Twin Register (NTR), Male, Genome-wide association study, Logistic regression, Cohort Studies, Odds Ratio, pleiotropic genetic effects, Netherlands, Psychiatry, education.field_of_study, Likelihood Functions, Single Nucleotide, Middle Aged, Psychiatry and Mental health, educational attainment, depression, Major depressive disorder, Educational Status, Regression Analysis, Female, Psychology, Adult, Estonia, medicine.medical_specialty, Biochemistry & Molecular Biology, Aged, Depressive Disorder, Major/epidemiology, Depressive Disorder, Major/genetics, Depressive Disorder, Major/psychology, Estonia/epidemiology, Gene-Environment Interaction, Genetic Association Studies, Genotype, Humans, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Psychiatric Status Rating Scales, Concordance, Population, SNP, Single-nucleotide polymorphism, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, mental disorders, medicine, Polymorphism, education, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, major depressive disorder, ta1184, Neurosciences, Major, Odds ratio, medicine.disease, ta3124, Neurosciences & Neurology, polymorphisms, Demography
Abstract: An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed
Published: 2015
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42. [Recurrent fugues, also consider epilepsy].

Author: Broekmeulen J, Schulkens J, de Leeuw C, and Hoff EI
Subjects: Humans, Male, Aged, Diagnosis, Differential, Electroencephalography, Epilepsy diagnosis, Recurrence, Dissociative Disorders diagnosis, Dissociative Disorders psychology, Status Epilepticus diagnosis
Abstract: We discuss an interesting case of a 65-year-old man with multiple dissociative episodes which previously had been assessed as fugues. After evaluation in the memory clinic these episodes appeared to be generalized epileptic seizures, with an electro-encephalographic diagnosis of non-convulsive status epilepticus. Throughout this case, the different features that characterize an epileptic versus a psychiatric etiology are being discussed as well as other differential diagnostic considerations. A non-convulsive status epilepticus is a treatable disease which can being missed often. With this case, we intend to create awareness and clues to recognize this disease.
Published: 2025

43. Optimized Dosing and Delivery of Bacteriophage Therapy for Wound Infections.

Author: Lin YH, Dharmaraj T, Chen Q, Echterhof A, Manasherob R, Zhang LJ, de Leeuw C, Peterson NA, Stannard W, Li Z, Hajfathalian M, Hargil A, Martinez HA, Pourtois J, Chang THW, Blankenberg FG, Amanatullah D, Chaudhuri O, and Bollyky PL
Abstract: Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, the optimal dosing and delivery strategies for phage therapy remain unclear. In a mouse wound infection model, we investigated the impact of dose, frequency, and administration route on the efficacy of phage therapy. We find that topical but not intravenous delivery is effective in this model. High-doses of phage reduces bacterial burden more effectively than low-doses, and repeated dosing achieves the highest eradication rates. Building on these insights, we developed "HydroPhage", a hyaluronan-based hydrogel system that uses dynamic covalent crosslinking to deliver high-titre phages over one week. HydroPhage eradicates infections five times more effectively than intravenous injection. We conclude that hydrogel-based sustained phage delivery enhances the efficacy of phage therapy and offers a practical, well-tolerated option for topical application., Competing Interests: Competing interests The authors declare no competing interests
Published: 2024
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44. The Genetic Architecture of the Human Corpus Callosum and its Subregions.

Author: Bhatt RR, Gadewar SP, Shetty A, Ba Gari I, Haddad E, Javid S, Ramesh A, Nourollahimoghadam E, Zhu AH, de Leeuw C, Thompson PM, Medland SE, and Jahanshad N
Abstract: The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses, performing associative/executive functions, and representing information in multiple dimensions. Understanding which genetic variants underpin corpus callosum morphometry, and their shared influence on cortical structure and susceptibility to neuropsychiatric disorders, can provide molecular insights into the CC's role in mediating cortical development and its contribution to neuropsychiatric disease. To characterize the morphometry of the midsagittal corpus callosum, we developed a publicly available artificial intelligence based tool to extract, parcellate, and calculate its total and regional area and thickness. Using the UK Biobank (UKB) and the Adolescent Brain Cognitive Development study (ABCD), we extracted measures of midsagittal corpus callosum morphometry and performed a genome-wide association study (GWAS) meta-analysis of European participants (combined N = 46,685). We then examined evidence for generalization to the non-European participants of the UKB and ABCD cohorts (combined N = 7,040). Post-GWAS analyses implicate prenatal intracellular organization and cell growth patterns, and high heritability in regions of open chromatin, suggesting transcriptional activity regulation in early development. Results suggest programmed cell death mediated by the immune system drives the thinning of the posterior body and isthmus. Global and local genetic overlap, along with causal genetic liability, between the corpus callosum, cerebral cortex, and neuropsychiatric disorders such as attention-deficit/hyperactivity and bipolar disorders were identified. These results provide insight into variability of corpus callosum development, its genetic influence on the cerebral cortex, and biological mechanisms related to neuropsychiatric dysfunction., Competing Interests: Ethics Declarations Competing Interests No authors have any other conflicts of interest to disclose.
Published: 2024
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45. Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets.

Author: Frei O, Hindley G, Shadrin AA, van der Meer D, Akdeniz BC, Hagen E, Cheng W, O'Connell KS, Bahrami S, Parker N, Smeland OB, Holland D, de Leeuw C, Posthuma D, Andreassen OA, and Dale AM
Subjects: Humans, Multifactorial Inheritance genetics, Models, Genetic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Predisposition to Disease, Chromosome Mapping methods, Computer Simulation, Quantitative Trait, Heritable, Genome-Wide Association Study methods, Schizophrenia genetics, Linkage Disequilibrium
Abstract: While genome-wide association studies are increasingly successful in discovering genomic loci associated with complex human traits and disorders, the biological interpretation of these findings remains challenging. Here we developed the GSA-MiXeR analytical tool for gene set analysis (GSA), which fits a model for the heritability of individual genes, accounting for linkage disequilibrium across variants and allowing the quantification of partitioned heritability and fold enrichment for small gene sets. We validated the method using extensive simulations and sensitivity analyses. When applied to a diverse selection of complex traits and disorders, including schizophrenia, GSA-MiXeR prioritizes gene sets with greater biological specificity compared to standard GSA approaches, implicating voltage-gated calcium channel function and dopaminergic signaling for schizophrenia. Such biologically relevant gene sets, often with fewer than ten genes, are more likely to provide insights into the pathobiology of complex diseases and highlight potential drug targets., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2024
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46. Shifts in dominance of benthic communities along a gradient of water temperature and turbidity in tropical coastal ecosystems.

Author: Aji LP, Maas DL, Capriati A, Ahmad A, de Leeuw C, and Becking LE
Subjects: Animals, Indonesia, Lakes chemistry, Biodiversity, Anthozoa physiology, Coral Reefs, Temperature, Ecosystem, Tropical Climate
Abstract: Tropical coastal benthic communities will change in species composition and relative dominance due to global (e.g., increasing water temperature) and local (e.g., increasing terrestrial influence due to land-based activity) stressors. This study aimed to gain insight into possible trajectories of coastal benthic assemblages in Raja Ampat, Indonesia, by studying coral reefs at varying distances from human activities and marine lakes with high turbidity in three temperature categories (<31 °C, 31-32 °C, and >32 °C). The benthic community diversity and relative coverage of major benthic groups were quantified via replicate photo transects. The composition of benthic assemblages varied significantly among the reef and marine lake habitats. The marine lakes <31 °C contained hard coral, crustose coralline algae (CCA), and turf algae with coverages similar to those found in the coral reefs (17.4-18.8% hard coral, 3.5-26.3% CCA, and 15-15.5% turf algae, respectively), while the higher temperature marine lakes (31-32 °C and >32 °C) did not harbor hard coral or CCA. Benthic composition in the reefs was significantly influenced by geographic distance among sites but not by human activity or depth. Benthic composition in the marine lakes appeared to be structured by temperature, salinity, and degree of connection to the adjacent sea. Our results suggest that beyond a certain temperature (>31 °C), benthic communities shift away from coral dominance, but new outcomes of assemblages can be highly distinct, with a possible varied dominance of macroalgae, benthic cyanobacterial mats, or filter feeders such as bivalves and tubeworms. This study illustrates the possible use of marine lake model systems to gain insight into shifts in the benthic community structure of tropical coastal ecosystems if hard corals are no longer dominant., Competing Interests: The authors declare there are no competing interests., (©2024 Aji et al.)
Published: 2024
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47. Insights into soft short circuit-based degradation of lithium metal batteries.

Author: Menkin S, Fritzke JB, Larner R, de Leeuw C, Choi Y, Gunnarsdóttir AB, and Grey CP
Abstract: The demand for electric vehicles with extended ranges has created a renaissance of interest in replacing the common metal-ion with higher energy-density metal-anode batteries. However, the potential battery safety issues associated with lithium metal must be addressed to enable lithium metal battery chemistries. A considerable performance gap between lithium (Li) symmetric cells and practical Li batteries motivated us to explore the correlation between the shape of voltage traces and degradation. We coupled impedance spectroscopy and operando NMR and used the new approach to show that transient ( i.e. , soft) shorts form in realistic conditions for battery applications; however, they are typically overlooked, as their electrochemical signatures are often not distinct. The typical rectangular-shaped voltage trace, widely considered ideal, was proven, under the conditions studied here, to be a result of soft shorts. Recoverable soft-shorted cells were demonstrated during a symmetric cell polarisation experiment, defining a new type of critical current density: the current density at which the soft shorts are not reversible. Moreover, we demonstrated that soft shorts, detected via electrochemical impedance spectroscopy (EIS) and validated via operando NMR, are predictive towards the formation of hard shorts, showing the potential use of EIS as a relatively low-cost and non-destructive method for early detection of catastrophic shorts and battery failure while demonstrating the strength of operando NMR as a research tool for metal plating in lithium batteries.
Published: 2024
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48. On the interpretation of transcriptome-wide association studies.

Author: de Leeuw C, Werme J, Savage JE, Peyrot WJ, and Posthuma D
Subjects: Chromosome Mapping, Computer Simulation, Data Analysis, Genome-Wide Association Study, Transcriptome genetics
Abstract: Transcriptome-wide association studies (TWAS) aim to detect relationships between gene expression and a phenotype, and are commonly used for secondary analysis of genome-wide association study (GWAS) results. Results from TWAS analyses are often interpreted as indicating a genetic relationship between gene expression and a phenotype, but this interpretation is not consistent with the null hypothesis that is evaluated in the traditional TWAS framework. In this study we provide a mathematical outline of this TWAS framework, and elucidate what interpretations are warranted given the null hypothesis it actually tests. We then use both simulations and real data analysis to assess the implications of misinterpreting TWAS results as indicative of a genetic relationship between gene expression and the phenotype. Our simulation results show considerably inflated type 1 error rates for TWAS when interpreted this way, with 41% of significant TWAS associations detected in the real data analysis found to have insufficient statistical evidence to infer such a relationship. This demonstrates that in current implementations, TWAS cannot reliably be used to investigate genetic relationships between gene expression and a phenotype, but that local genetic correlation analysis can serve as a potential alternative., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Leeuw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2023
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49. Exploring the genetic overlap between twelve psychiatric disorders.

Author: Romero C, Werme J, Jansen PR, Gelernter J, Stein MB, Levey D, Polimanti R, de Leeuw C, Posthuma D, Nagel M, and van der Sluis S
Subjects: Humans, Genomics, Mental Disorders genetics
Abstract: The widespread comorbidity among psychiatric disorders demonstrated in epidemiological studies 1-5 is mirrored by non-zero, positive genetic correlations from large-scale genetic studies 6-10 . To identify shared biological processes underpinning this observed phenotypic and genetic covariance and enhance molecular characterization of general psychiatric disorder liability 11-13 , we used several strategies aimed at uncovering pleiotropic, that is, cross-trait-associated, single-nucleotide polymorphisms (SNPs), genes and biological pathways. We conducted cross-trait meta-analysis on 12 psychiatric disorders to identify pleiotropic SNPs. The meta-analytic signal was driven by schizophrenia, hampering interpretation and joint biological characterization of the cross-trait meta-analytic signal. Subsequent pairwise comparisons of psychiatric disorders identified substantial pleiotropic overlap, but mainly among pairs of psychiatric disorders, and mainly at less stringent P-value thresholds. Only annotations related to evolutionarily conserved genomic regions were significant for multiple (9 out of 12) psychiatric disorders. Overall, identification of shared biological mechanisms remains challenging due to variation in power and genetic architecture between psychiatric disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2022
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50. Disentangling Genetic Risks for Metabolic Syndrome.

Author: van Walree ES, Jansen IE, Bell NY, Savage JE, de Leeuw C, Nieuwdorp M, van der Sluis S, and Posthuma D
Subjects: Humans, Cholesterol, HDL, Genome-Wide Association Study, Risk Factors, Triglycerides, Waist Circumference, Blood Pressure, Glucose, Blood Glucose, Metabolic Syndrome epidemiology, Diabetes Mellitus, Type 2 genetics, Fenofibrate
Abstract: A quarter of the world's population is estimated to meet the criteria for metabolic syndrome (MetS), a cluster of cardiometabolic risk factors that promote development of coronary artery disease and type 2 diabetes, leading to increased risk of premature death and significant health costs. In this study we investigate whether the genetics associated with MetS components mirror their phenotypic clustering. A multivariate approach that leverages genetic correlations of fasting glucose, HDL cholesterol, systolic blood pressure, triglycerides, and waist circumference was used, which revealed that these genetic correlations are best captured by a genetic one factor model. The common genetic factor genome-wide association study (GWAS) detects 235 associated loci, 174 more than the largest GWAS on MetS to date. Of these loci, 53 (22.5%) overlap with loci identified for two or more MetS components, indicating that MetS is a complex, heterogeneous disorder. Associated loci harbor genes that show increased expression in the brain, especially in GABAergic and dopaminergic neurons. A polygenic risk score drafted from the MetS factor GWAS predicts 5.9% of the variance in MetS. These results provide mechanistic insights into the genetics of MetS and suggestions for drug targets, especially fenofibrate, which has the promise of tackling multiple MetS components., (© 2022 by the American Diabetes Association.)
Published: 2022
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