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13 results on '"Eijk, K.R. van"'

1. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author

Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., Dupuis, L., Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., and Dupuis, L.

Abstract

Item does not contain fulltext

Published
2023

2. Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis.

Author

Groot, E.L. de, Ossewaarde-van Norel, J., Boer, J.H. de, Hiddingh, S., Bakker, B., Huet, R.A.C. van, Dam-van Loon, N.H. Ten, Thiadens, A.A.H.J., Meester-Smoor, M.A., Jong-Hesse, Y. de, Los, L.I., Hollander, A.I. den, Boon, C.J.F., Kiemeney, B., Eijk, K.R. van, Bakker, M.K., Hoyng, C.B., Kuiper, J.J.W., Groot, E.L. de, Ossewaarde-van Norel, J., Boer, J.H. de, Hiddingh, S., Bakker, B., Huet, R.A.C. van, Dam-van Loon, N.H. Ten, Thiadens, A.A.H.J., Meester-Smoor, M.A., Jong-Hesse, Y. de, Los, L.I., Hollander, A.I. den, Boon, C.J.F., Kiemeney, B., Eijk, K.R. van, Bakker, M.K., Hoyng, C.B., and Kuiper, J.J.W.

Abstract

Item does not contain fulltext, IMPORTANCE: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. OBJECTIVE: To identify the genes and pathways associated with idiopathic MFC. DESIGN, SETTING, AND PARTICIPANTS: This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022. MAIN OUTCOMES AND MEASURES: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. RESULTS: This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysi

Published
2023

3. Genome-Wide Association meta-analysis of age at first cannabis use

Author

Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., Derks, E.M., Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., and Derks, E.M.

Abstract

Contains fulltext : 195854.pdf (publisher's version ) (Closed access), Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants. Methods: A twin-based heritability analysis using 8,055 twins from three cohorts was performed. We then carried-out a genome wide survival meta-analysis of age at first cannabis use in a discovery sample of 24,953 individuals from nine European, North American, and Australian cohorts, and a replication sample of 3,735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% (95% confidence interval [CI] 19-60%). Shared and unique environmental factors explained 39% (95% CI 20-56%) and 22% (95% CI 16-29%). The genome wide survival meta-analysis identified five SNPs on chromosome 16 within the Calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high LD (r2>0.8) with the strongest association at the intronic variant rs1574587 (P=4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P=1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been previously associated with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in Western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Published
2018

4. Genome-Wide Association meta-analysis of age at first cannabis use

Author

Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., Derks, E.M., Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., and Derks, E.M.

Abstract

Contains fulltext : 195854.pdf (publisher's version ) (Closed access), Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants. Methods: A twin-based heritability analysis using 8,055 twins from three cohorts was performed. We then carried-out a genome wide survival meta-analysis of age at first cannabis use in a discovery sample of 24,953 individuals from nine European, North American, and Australian cohorts, and a replication sample of 3,735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% (95% confidence interval [CI] 19-60%). Shared and unique environmental factors explained 39% (95% CI 20-56%) and 22% (95% CI 16-29%). The genome wide survival meta-analysis identified five SNPs on chromosome 16 within the Calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high LD (r2>0.8) with the strongest association at the intronic variant rs1574587 (P=4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P=1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been previously associated with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in Western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Published
2018

5. Genome-Wide Association meta-analysis of age at first cannabis use

Author

Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., Derks, E.M., Minica, C.C., Verweij, K.J.H., Most, P.J. van der, Mbarek, H., Bernard, M., Eijk, K.R. van, Lind, P.A., Liu, M.Z., Maciejewski, D.F., Palviainen, T., Sánchez-Mora, C., Sherva, R., Taylor, M., Walters, R.K., Abdellaoui, A., Bigdeli, T.B., Branje, S.J.T., Brown, S.A., Casas, M., Corley, R.P., Smith, G.D., Davies, G.E., Ehli, E.A., Farrer, L.A., Fedko, I.O., Garcia-Martinez, I., Gordon, S.D., Hartman, C.A., Heath, A.C., Hickie, I.B., Hickman, M., Hopfer, C.J., Hottenga, J.J., Kahn, R.S., Kaprio, J., Korhonen, T., Kranzler, H.R., Krauter, K., Lier, P.A.C. van, Madden, P.A.F., Medland, S.E., Neale, M.C., Meeus, W.H.J., Montgomery, G.W., Nolte, I.M., Oldehinkel, A.J., Pausova, Z., Ramos-Quiroga, J.A., Richarte, V., Rose, R.J., Shin, J., Stallings, M.C., Wall, T.L., Ware, J.J., Wright, M.J., Zhao, H., Koot, J.M., Paus, T., Hewitt, J.K., Ribasés, M., Loukola, A., Boks, M.P.M., Snieder, H., Munafò, M.R., Gelernter, J., Boomsma, D.I., Martin, N.G., Gillespie, N.A., Vink, J.M., and Derks, E.M.

Abstract

Contains fulltext : 195854.pdf (publisher's version ) (Closed access), Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants. Methods: A twin-based heritability analysis using 8,055 twins from three cohorts was performed. We then carried-out a genome wide survival meta-analysis of age at first cannabis use in a discovery sample of 24,953 individuals from nine European, North American, and Australian cohorts, and a replication sample of 3,735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% (95% confidence interval [CI] 19-60%). Shared and unique environmental factors explained 39% (95% CI 20-56%) and 22% (95% CI 16-29%). The genome wide survival meta-analysis identified five SNPs on chromosome 16 within the Calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high LD (r2>0.8) with the strongest association at the intronic variant rs1574587 (P=4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P=1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been previously associated with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in Western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Published
2018

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

Author

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

Abstract

Contains fulltext : 156357.pdf (publisher's version ) (Open Access), Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10-8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Published
2016

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

Author

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

Abstract

Contains fulltext : 156357.pdf (publisher's version ) (Open Access), Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10-8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Published
2016

8. Common genetic variants influence human subcortical brain structures

Author

Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., Fernandez, G.S.E., Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., and Fernandez, G.S.E.

Abstract

Contains fulltext : 144426.pdf (publisher's version ) (Closed access) Contains fulltext : 144426pre.pdf (preprint version ) (Open Access), The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Published
2015

9. Common genetic variants influence human subcortical brain structures

Author

Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., Fernandez, G.S.E., Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., and Fernandez, G.S.E.

Abstract

Contains fulltext : 144426.pdf (publisher's version ) (Closed access) Contains fulltext : 144426pre.pdf (preprint version ) (Open Access), The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Published
2015

10. Common genetic variants influence human subcortical brain structures

Author

Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., Fernandez, G.S.E., Hibar, D.P., Stein, J.L., Renteria, M.E., Arias Vasquez, A., Desrivieres, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J.B., Brown, A.A., Chakravarty, M.M., Chen, Q., Ching, C.R., Cuellar-Partida, G., Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T.M., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santianez, R., Rose, E.J., Salami, A., Samann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., Donkelaar, M.M.J. van, Eijk, K.R. van, Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M., Hartberg, C.B., Haukvik, U.K., Heister, A.J., Hoehn, D., Kasperaviciute, D., Liewald, D.C., Lopez, L.M., Makkinje, R.R., Matarin, M., Naber, M., McKay, D.R., Needham, M., Nugent, A.C., Putz, B., Royle, N.A., Shen, L., Sprooten, E., Trabzuni, D., Marel, S.S. van der, Hulzen, K.J.E. van, Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., Fisher, S.E., Buitelaar, J.K., and Fernandez, G.S.E.

Abstract

Contains fulltext : 144426.pdf (publisher's version ) (Closed access) Contains fulltext : 144426pre.pdf (preprint version ) (Open Access), The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Published
2015

11. Increased paternal age and the influence on burden of genomic copy number variation in the general population

Author

Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., Ophoff, R.A., Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., and Ophoff, R.A.

Abstract

Item does not contain fulltext, Genomic copy number variations (CNVs) and increased parental age are both associated with the risk to develop a variety of clinical neuropsychiatric disorders such as autism, schizophrenia and bipolar disorder. At the same time, it has been shown that the rate of transmitted de novo single nucleotide mutations is increased with paternal age. To address whether paternal age also affects the burden of structural genomic deletions and duplications, we examined various types of CNV burden in a large population sample from the Netherlands. Healthy participants with parental age information (n = 6,773) were collected at different University Medical Centers. CNVs were called with the PennCNV algorithm using Illumina genome-wide SNP array data. We observed no evidence in support of a paternal age effect on CNV load in the offspring. Our results were negative for global measures as well as several proxies for de novo CNV events in this unique sample. While recent studies suggest de novo single nucleotide mutation rate to be dominated by the age of the father at conception, our results strongly suggest that at the level of global CNV burden there is no influence of increased paternal age. While it remains possible that local genomic effects may exist for specific phenotypes, this study indicates that global CNV burden and increased father's age may be independent disease risk factors.

Published
2013

12. Increased paternal age and the influence on burden of genomic copy number variation in the general population

Author

Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., Ophoff, R.A., Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., and Ophoff, R.A.

Abstract

Item does not contain fulltext, Genomic copy number variations (CNVs) and increased parental age are both associated with the risk to develop a variety of clinical neuropsychiatric disorders such as autism, schizophrenia and bipolar disorder. At the same time, it has been shown that the rate of transmitted de novo single nucleotide mutations is increased with paternal age. To address whether paternal age also affects the burden of structural genomic deletions and duplications, we examined various types of CNV burden in a large population sample from the Netherlands. Healthy participants with parental age information (n = 6,773) were collected at different University Medical Centers. CNVs were called with the PennCNV algorithm using Illumina genome-wide SNP array data. We observed no evidence in support of a paternal age effect on CNV load in the offspring. Our results were negative for global measures as well as several proxies for de novo CNV events in this unique sample. While recent studies suggest de novo single nucleotide mutation rate to be dominated by the age of the father at conception, our results strongly suggest that at the level of global CNV burden there is no influence of increased paternal age. While it remains possible that local genomic effects may exist for specific phenotypes, this study indicates that global CNV burden and increased father's age may be independent disease risk factors.

Published
2013

13. Increased paternal age and the influence on burden of genomic copy number variation in the general population

Author

Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., Ophoff, R.A., Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P., Eijk, K.R. van, Veldink, J.H., Hennekam, E.A., Vorstman, J.A., Mulder, F., Tiemeier, H., Uitterlinden, A.G., Kiemeney, L.A.L.M., Berg, L.H. van den, Kahn, R.S., Sabatti, C., and Ophoff, R.A.

Abstract

Item does not contain fulltext, Genomic copy number variations (CNVs) and increased parental age are both associated with the risk to develop a variety of clinical neuropsychiatric disorders such as autism, schizophrenia and bipolar disorder. At the same time, it has been shown that the rate of transmitted de novo single nucleotide mutations is increased with paternal age. To address whether paternal age also affects the burden of structural genomic deletions and duplications, we examined various types of CNV burden in a large population sample from the Netherlands. Healthy participants with parental age information (n = 6,773) were collected at different University Medical Centers. CNVs were called with the PennCNV algorithm using Illumina genome-wide SNP array data. We observed no evidence in support of a paternal age effect on CNV load in the offspring. Our results were negative for global measures as well as several proxies for de novo CNV events in this unique sample. While recent studies suggest de novo single nucleotide mutation rate to be dominated by the age of the father at conception, our results strongly suggest that at the level of global CNV burden there is no influence of increased paternal age. While it remains possible that local genomic effects may exist for specific phenotypes, this study indicates that global CNV burden and increased father's age may be independent disease risk factors.

Published
2013

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