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21 results on '"Agbessi, Mawussé"'

1. OTTERS: a powerful TWAS framework leveraging summary-level reference data

Author

Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., Yang, Jingjing, Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., and Yang, Jingjing

Abstract

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies., Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w

Published
2023
Full Text
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2. OTTERS: a powerful TWAS framework leveraging summary-level reference data

Author

Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., Yang, Jingjing, Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., and Yang, Jingjing

Abstract

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies., Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w

Published
2023
Full Text
View/download PDF

3. OTTERS:a powerful TWAS framework leveraging summary-level reference data

Author

Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Scholz, Markus, van Meurs, Joyce, Verlouw, Joost, Yang, Jian, Yang, Jingjing, Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Scholz, Markus, van Meurs, Joyce, Verlouw, Joost, Yang, Jian, and Yang, Jingjing

Abstract

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.

Published
2023

4. Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control

Author

Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Tremblay, Johanne, Haloui, Mounsif, Attaoua, Redha, Tahir, Ramzan, Hishmih, Camil, Harvey, François, Marois-Blanchet, François Christophe, Long, Carole, Simon, Paul, Santucci, Lara, Hizel, Candan, Chalmers, John, Marre, Michel, Harrap, Stephen, Cífková, Renata, Krajčoviechová, Alena, Matthews, David R., Williams, Bryan, Poulter, Neil, Zoungas, Sophia, Colagiuri, Stephen, Mancia, Giuseppe, Grobbee, Diederick E., Rodgers, Anthony, Liu, Liusheng, Agbessi, Mawussé, Bruat, Vanessa, Favé, Marie Julie, Harwood, Michelle P., Awadalla, Philip, Woodward, Mark, Hussin, Julie G., Hamet, Pavel, Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Tremblay, Johanne, Haloui, Mounsif, Attaoua, Redha, Tahir, Ramzan, Hishmih, Camil, Harvey, François, Marois-Blanchet, François Christophe, Long, Carole, Simon, Paul, Santucci, Lara, Hizel, Candan, Chalmers, John, Marre, Michel, Harrap, Stephen, Cífková, Renata, Krajčoviechová, Alena, Matthews, David R., Williams, Bryan, Poulter, Neil, Zoungas, Sophia, Colagiuri, Stephen, Mancia, Giuseppe, Grobbee, Diederick E., Rodgers, Anthony, Liu, Liusheng, Agbessi, Mawussé, Bruat, Vanessa, Favé, Marie Julie, Harwood, Michelle P., Awadalla, Philip, Woodward, Mark, Hussin, Julie G., and Hamet, Pavel

Published
2021

5. Correction to: Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control (Diabetologia, (2021), 64, 9, (2012-2025), 10.1007/s00125-021-05491-7)

Author

Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Tremblay, Johanne, Haloui, Mounsif, Attaoua, Redha, Tahir, Ramzan, Hishmih, Camil, Harvey, François, Marois-Blanchet, François Christophe, Long, Carole, Simon, Paul, Santucci, Lara, Hizel, Candan, Chalmers, John, Marre, Michel, Harrap, Stephen, Cífková, Renata, Krajčoviechová, Alena, Matthews, David R., Williams, Bryan, Poulter, Neil, Zoungas, Sophia, Colagiuri, Stephen, Mancia, Giuseppe, Grobbee, Diederick E., Rodgers, Anthony, Liu, Liusheng, Agbessi, Mawussé, Bruat, Vanessa, Favé, Marie Julie, Harwood, Michelle P., Awadalla, Philip, Woodward, Mark, Hussin, Julie G., Hamet, Pavel, Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Tremblay, Johanne, Haloui, Mounsif, Attaoua, Redha, Tahir, Ramzan, Hishmih, Camil, Harvey, François, Marois-Blanchet, François Christophe, Long, Carole, Simon, Paul, Santucci, Lara, Hizel, Candan, Chalmers, John, Marre, Michel, Harrap, Stephen, Cífková, Renata, Krajčoviechová, Alena, Matthews, David R., Williams, Bryan, Poulter, Neil, Zoungas, Sophia, Colagiuri, Stephen, Mancia, Giuseppe, Grobbee, Diederick E., Rodgers, Anthony, Liu, Liusheng, Agbessi, Mawussé, Bruat, Vanessa, Favé, Marie Julie, Harwood, Michelle P., Awadalla, Philip, Woodward, Mark, Hussin, Julie G., and Hamet, Pavel

Published
2021

6. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author

Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Møllegaard, Stine, Pers, Tune H, Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Møllegaard, Stine, and Pers, Tune H

Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Published
2021

7. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author

Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W.J.H., Stehouwer, Coen D.A., van Greevenbroek, Marleen, van der Kallen, Carla, Schalkwijk, Casper, eQTLgen Consortium, BIOS Consortium, Cohort collection, Data Generation, Data management and computational infrastructure, Data Analysis Group, Human Reproductive Behaviour Consortium, Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W.J.H., Stehouwer, Coen D.A., van Greevenbroek, Marleen, van der Kallen, Carla, Schalkwijk, Casper, eQTLgen Consortium, BIOS Consortium, Cohort collection, Data Generation, Data management and computational infrastructure, Data Analysis Group, and Human Reproductive Behaviour Consortium

Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Published
2021

8. Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Author

Hammerschlag, Anke R., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-nurasyid, Martina, Nauck, Matthias, Nivard, Michel, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Van Iterson, Maarten, Van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., Van Der Kallen, Carla J.h., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H.eka D., Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., Hoen, Peter-bram ‘t, Hammerschlag, Anke R., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-nurasyid, Martina, Nauck, Matthias, Nivard, Michel, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Van Iterson, Maarten, Van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., Van Der Kallen, Carla J.h., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H.eka D., Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., and Hoen, Peter-bram ‘t

Abstract

Background: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels. Methods: We applied summary-data–based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data–based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels. Results: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before. Conclusions: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Published
2020
Full Text
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9. Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies

Author

Hammerschlag, Anke R., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-nurasyid, Martina, Nauck, Matthias, Nivard, Michel, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Van Iterson, Maarten, Van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., Van Der Kallen, Carla J.h., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H.eka D., Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., Hoen, Peter-bram ‘t, Hammerschlag, Anke R., Byrne, Enda M., Bartels, Meike, Wray, Naomi R., Middeldorp, Christel M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan T., Hemani, Gibran, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-nurasyid, Martina, Nauck, Matthias, Nivard, Michel, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, P. Eline, Stehouwer, Coen D.a., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A.c., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Van Iterson, Maarten, Van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Van Dongen, Jenny, Hottenga, Jouke J., Van Greevenbroek, Marleen Mj., Van Der Kallen, Carla J.h., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H.eka D., Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Van Galen, Michiel, Bot, Jan, Zhernakova, Daria V., Hof, Peter Van ‘t, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., Van Zwet, Erik. W., and Hoen, Peter-bram ‘t

Abstract

Background: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels. Methods: We applied summary-data–based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data–based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels. Results: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before. Conclusions: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Published
2020
Full Text
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10. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author

Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal, Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J.van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter Bram t., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J.van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J.van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A.L.M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C.M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, McMahon, George, Nyholt, Dale R., Smith, Jennifer A., Martin, Nicholas G., Medland, Sarah E., Clark, David W., other, and, Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal, Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J.van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter Bram t., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J.van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J.van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A.L.M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C.M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, McMahon, George, Nyholt, Dale R., Smith, Jennifer A., Martin, Nicholas G., Medland, Sarah E., Clark, David W., and other, and

Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (∣r̂ g∣ ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Published
2019

11. Relaxed selection during a recent human expansion

Author

Peischl, Stephan, Dupanloup, Isabelle, Foucal, Adrien, Jomphe, Michèle, Bruat, Vanessa, Grenier, Jean-Christophe, Gouy, Alexandre, Gilbert, K J, Gbeha, Elias, Bosshard, Lars, Hip-Ki, Elodie, Agbessi, Mawussé, Hodgkinson, Alan, Vézina, Hélène, Awadalla, Philip, Excoffier, Laurent, Peischl, Stephan, Dupanloup, Isabelle, Foucal, Adrien, Jomphe, Michèle, Bruat, Vanessa, Grenier, Jean-Christophe, Gouy, Alexandre, Gilbert, K J, Gbeha, Elias, Bosshard, Lars, Hip-Ki, Elodie, Agbessi, Mawussé, Hodgkinson, Alan, Vézina, Hélène, Awadalla, Philip, and Excoffier, Laurent

Abstract

Peischl et al. explore the way evolutionary forces shape genetic variability in expanding human populations. Over a few generations of separate evolution... Humans have colonized the planet through a series of range expansions, which deeply impacted genetic diversity in newly settled areas and potentially increased the frequency of deleterious mutations on expanding wave fronts. To test this prediction, we studied the genomic diversity of French Canadians who colonized Quebec in the 17th century. We used historical information and records from ∼4000 ascending genealogies to select individuals whose ancestors lived mostly on the colonizing wave front and individuals whose ancestors remained in the core of the settlement. Comparison of exomic diversity reveals that: (i) both new and low-frequency variants are significantly more deleterious in front than in core individuals, (ii) equally deleterious mutations are at higher frequencies in front individuals, and (iii) front individuals are two times more likely to be homozygous for rare very deleterious mutations present in Europeans. These differences have emerged in the past six to nine generations and cannot be explained by differential inbreeding, but are consistent with relaxed selection mainly due to higher rates of genetic drift on the wave front. Demographic inference and modeling of the evolution of rare variants suggest lower effective size on the front, and lead to an estimation of selection coefficients that increase with conservation scores. Even though range expansions have had a relatively limited impact on the overall fitness of French Canadians, they could explain the higher prevalence of recessive genetic diseases in recently settled regions of Quebec.

Published
2018
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12. Gene coexpression network analysis of oil biosynthesis in an interspecific backcross of oil palm

Author

Guérin, Chloé, Joët, Thierry, Serret, Julien, Lashermes, Philippe, Vaissayre, Virginie, Agbessi, Mawussé D.T., Beulé, Thierry, Severac, Dany, Amblard, Philippe, Tregear, James, Durand-Gasselin, Tristan, Morcillo, Fabienne, Dussert, Stéphane, Guérin, Chloé, Joët, Thierry, Serret, Julien, Lashermes, Philippe, Vaissayre, Virginie, Agbessi, Mawussé D.T., Beulé, Thierry, Severac, Dany, Amblard, Philippe, Tregear, James, Durand-Gasselin, Tristan, Morcillo, Fabienne, and Dussert, Stéphane

Abstract

Global demand for vegetable oils is increasing at a dramatic rate, while our understanding of the regulation of oil biosynthesis in plants remains limited. To gain insights into the mechanisms that govern oil synthesis and fatty acid (FA) composition in the oil palm fruit, we used a multilevel approach combining gene coexpression analysis, quantification of allele-specific expression and joint multivariate analysis of transcriptomic and lipid data, in an interspecific backcross population between the African oil palm, Elaeis guineensis, and the American oil palm, Elaeis oleifera, which display contrasting oil contents and FA compositions. The gene coexpression network produced revealed tight transcriptional coordination of fatty acid synthesis (FAS) in the plastid with sugar sensing, plastidial glycolysis, transient starch storage and carbon recapture pathways. It also revealed a concerted regulation, along with FAS, of both the transfer of nascent FA to the endoplasmic reticulum, where triacylglycerol assembly occurs, and of the production of glycerol-3-phosphate, which provides the backbone of triacylglycerols. Plastid biogenesis and auxin transport were the two other biological processes most tightly connected to FAS in the network. In addition to WRINKLED1, a transcription factor (TF) known to activate FAS genes, two novel TFs, termed NF-YB-1 and ZFP-1, were found at the core of the FAS module. The saturated FA content of palm oil appeared to vary above all in relation to the level of transcripts of the gene coding for β-ketoacyl-acyl carrier protein synthase II. Our findings should facilitate the development of breeding and engineering strategies in this and other oil crops.

Published
2016

13. Gene coexpression network analysis of oil biosynthesis in an interspecific backcross of oil palm

Author

Guérin, Chloé, Joët, Thierry, Serret, Julien, Lashermes, Philippe, Vaissayre, Virginie, Agbessi, Mawussé D.T., Beulé, Thierry, Severac, Dany, Amblard, Philippe, Tregear, James, Durand-Gasselin, Tristan, Morcillo, Fabienne, Dussert, Stéphane, Guérin, Chloé, Joët, Thierry, Serret, Julien, Lashermes, Philippe, Vaissayre, Virginie, Agbessi, Mawussé D.T., Beulé, Thierry, Severac, Dany, Amblard, Philippe, Tregear, James, Durand-Gasselin, Tristan, Morcillo, Fabienne, and Dussert, Stéphane

Abstract

Global demand for vegetable oils is increasing at a dramatic rate, while our understanding of the regulation of oil biosynthesis in plants remains limited. To gain insights into the mechanisms that govern oil synthesis and fatty acid (FA) composition in the oil palm fruit, we used a multilevel approach combining gene coexpression analysis, quantification of allele-specific expression and joint multivariate analysis of transcriptomic and lipid data, in an interspecific backcross population between the African oil palm, Elaeis guineensis, and the American oil palm, Elaeis oleifera, which display contrasting oil contents and FA compositions. The gene coexpression network produced revealed tight transcriptional coordination of fatty acid synthesis (FAS) in the plastid with sugar sensing, plastidial glycolysis, transient starch storage and carbon recapture pathways. It also revealed a concerted regulation, along with FAS, of both the transfer of nascent FA to the endoplasmic reticulum, where triacylglycerol assembly occurs, and of the production of glycerol-3-phosphate, which provides the backbone of triacylglycerols. Plastid biogenesis and auxin transport were the two other biological processes most tightly connected to FAS in the network. In addition to WRINKLED1, a transcription factor (TF) known to activate FAS genes, two novel TFs, termed NF-YB-1 and ZFP-1, were found at the core of the FAS module. The saturated FA content of palm oil appeared to vary above all in relation to the level of transcripts of the gene coding for β-ketoacyl-acyl carrier protein synthase II. Our findings should facilitate the development of breeding and engineering strategies in this and other oil crops. (Résumé d'auteur)

Published
2016

14. TOGGLE: toolbox for generic NGS analyses

Author

Monat, Cécile, Tranchant-Dubreuil, Christine, Kougbeadjo, Ayite, Farcy, Cédric, Ortega-Abboud, Enrique, Amanzougarene, Souhila, Ravel, Sébastien, Agbessi, Mawussé, Orjuela-Bouniol, Julie, Summo, Marilyne, Sabot, François, Monat, Cécile, Tranchant-Dubreuil, Christine, Kougbeadjo, Ayite, Farcy, Cédric, Ortega-Abboud, Enrique, Amanzougarene, Souhila, Ravel, Sébastien, Agbessi, Mawussé, Orjuela-Bouniol, Julie, Summo, Marilyne, and Sabot, François

Abstract

Background: The explosion of NGS (Next Generation Sequencing) sequence data requires a huge effort in Bioinformatics methods and analyses. The creation of dedicated, robust and reliable pipelines able to handle dozens of samples from raw FASTQ data to relevant biological data is a time-consuming task in all projects relying on NGS. To address this, we created a generic and modular toolbox for developing such pipelines. Results: TOGGLE (TOolbox for Generic nGs anaLysEs) is a suite of tools able to design pipelines that manage large sets of NGS softwares and utilities. Moreover, TOGGLE offers an easy way to manipulate the various options of the different softwares through the pipelines in using a single basic configuration file, which can be changed for each assay without having to change the code itself. We also describe one implementation of TOGGLE in a complete analysis pipeline designed for SNP discovery for large sets of genomic data, ready to use in different environments (from a single machine to HPC clusters). Conclusion: TOGGLE speeds up the creation of robust pipelines with reliable log tracking and data flow, for a large range of analyses. Moreover, it enables Biologists to concentrate on the biological relevance of results, and change the experimental conditions easily. The whole code and test data are available at https://github.com/SouthGreenPlatform/TOGGLE.

Published
2015

15. Genome-wide analysis of LTR-retrotransposons in oil palm

Author

Beulé, Thierry, Agbessi, Mawussé, Dussert, Stéphane, Jaligot, Estelle, Guyot, Romain, Beulé, Thierry, Agbessi, Mawussé, Dussert, Stéphane, Jaligot, Estelle, and Guyot, Romain

Abstract

Background: The oil palm (Elaeis guineensis Jacq.) is a major cultivated crop and the world's largest source of edible vegetable oil. The genus Elaeis comprises two species E. guineensis, the commercial African oil palm and E. oleifera, which is used in oil palm genetic breeding. The recent publication of both the African oil palm genome assembly and the first draft sequence of its Latin American relative now allows us to tackle the challenge of understanding the genome composition, structure and evolution of these palm genomes through the annotation of their repeated sequences. Methods: In this study, we identified, annotated and compared Transposable Elements (TE) from the African and Latin American oil palms. In a first step, Transposable Element databases were built through de novo detection in both genome sequences then the TE content of both genomes was estimated. Then putative full-length retrotransposons with Long Terminal Repeats (LTRs) were further identified in the E. guineensis genome for characterization of their structural diversity, copy number and chromosomal distribution. Finally, their relative expression in several tissues was determined through in silico analysis of publicly available transcriptome data. Results: Our results reveal a congruence in the transpositional history of LTR retrotransposons between E. oleifera and E. guineensis, especially the Sto-4 family. Also, we have identified and described 583 full-length LTR-retrotransposons in the Elaeis guineensis genome. Our work shows that these elements are most likely no longer mobile and that no recent insertion event has occurred. Moreover, the analysis of chromosomal distribution suggests a preferential insertion of Copia elements in gene-rich regions, whereas Gypsy elements appear to be evenly distributed throughout the genome. Conclusions: Considering the high proportion of LTR retrotransposon in the oil palm genome, our work will contribute to a greater understanding of their impact on

Published
2015

16. A story of flasks and flowers: new perspectives in the search for markers of the mantled somaclonal variation of oil palm [W552]

Author

Jaligot, Estelle, Wei Yeng Hooi, Richaud, Frédérique, Agbessi, Mawussé D.T., Yen Yen Kwan, Beulé, Thierry, Collin, Myriam, Debladis, Emilie, Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Alwee, Sharifah Shahrul Rabiah Syed, Rival, Alain, Jaligot, Estelle, Wei Yeng Hooi, Richaud, Frédérique, Agbessi, Mawussé D.T., Yen Yen Kwan, Beulé, Thierry, Collin, Myriam, Debladis, Emilie, Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Alwee, Sharifah Shahrul Rabiah Syed, and Rival, Alain

Abstract

The mantled somaclonal variation of oil palm (Elaeis guineensis Jacq.) is morphologically similar to mutants defective in MADS-box genes of the B-class. Indeed in such mutants male floral organs are converted into female ones and this can be observed in oil palm flowers of both sexes. The detrimental consequences of somaclonal variation on fruit set then oil yields and its unpredictable incidence in clonal progenies have prompted the search for early detection markers. More generally, a better understanding of the molecular mechanisms underlying the onset and the maintenance of this variant phenotype is needed. The mantledsomaclonal variation is observed only in clonal populations generated through somatic embryogenesis at a large commercial stage. Thus, because of the nature of the variation, research strategy must involve two parallel approaches aimed at studying simultaneously the in vitro stages of clonal palms production (the flask) and the in plantadevelopment of the reproductive organs which are affected by the phenotype (the flower). On both materials a novel combination of epigenetics approaches, high-throughput sequencing technologies and bioinformatics analyses now provide new insights into a complex developmental phenomenon. Our research work also paves the way for innovation and development oriented towards end-users in the palm oil industry. (Texte intégral)

Published
2015

17. TOGGLE: toolbox for generic NGS analyses

Author

Monat, Cécile, Tranchant-Dubreuil, Christine, Kougbeadjo, Ayite, Farcy, Cédric, Ortega-Abboud, Enrique, Amanzougarene, Souhila, Ravel, Sébastien, Agbessi, Mawussé, Orjuela-Bouniol, Julie, Summo, Marilyne, Sabot, François, Monat, Cécile, Tranchant-Dubreuil, Christine, Kougbeadjo, Ayite, Farcy, Cédric, Ortega-Abboud, Enrique, Amanzougarene, Souhila, Ravel, Sébastien, Agbessi, Mawussé, Orjuela-Bouniol, Julie, Summo, Marilyne, and Sabot, François

Abstract

Background: The explosion of NGS (Next Generation Sequencing) sequence data requires a huge effort in Bioinformatics methods and analyses. The creation of dedicated, robust and reliable pipelines able to handle dozens of samples from raw FASTQ data to relevant biological data is a time-consuming task in all projects relying on NGS. To address this, we created a generic and modular toolbox for developing such pipelines. Results: TOGGLE (TOolbox for Generic nGs anaLysEs) is a suite of tools able to design pipelines that manage large sets of NGS softwares and utilities. Moreover, TOGGLE offers an easy way to manipulate the various options of the different softwares through the pipelines in using a single basic configuration file, which can be changed for each assay without having to change the code itself. We also describe one implementation of TOGGLE in a complete analysis pipeline designed for SNP discovery for large sets of genomic data, ready to use in different environments (from a single machine to HPC clusters). Conclusion: TOGGLE speeds up the creation of robust pipelines with reliable log tracking and data flow, for a large range of analyses. Moreover, it enables Biologists to concentrate on the biological relevance of results, and change the experimental conditions easily. The whole code and test data are available at https://github.com/SouthGreenPlatform/TOGGLE.

Published
2015

18. Genome-wide analysis of LTR-retrotransposons in oil palm

Author

Beulé, Thierry, Agbessi, Mawussé, Dussert, Stéphane, Jaligot, Estelle, Guyot, Romain, Beulé, Thierry, Agbessi, Mawussé, Dussert, Stéphane, Jaligot, Estelle, and Guyot, Romain

Abstract

Background: The oil palm (Elaeis guineensis Jacq.) is a major cultivated crop and the world's largest source of edible vegetable oil. The genus Elaeis comprises two species E. guineensis, the commercial African oil palm and E. oleifera, which is used in oil palm genetic breeding. The recent publication of both the African oil palm genome assembly and the first draft sequence of its Latin American relative now allows us to tackle the challenge of understanding the genome composition, structure and evolution of these palm genomes through the annotation of their repeated sequences. Methods: In this study, we identified, annotated and compared Transposable Elements (TE) from the African and Latin American oil palms. In a first step, Transposable Element databases were built through de novo detection in both genome sequences then the TE content of both genomes was estimated. Then putative full-length retrotransposons with Long Terminal Repeats (LTRs) were further identified in the E. guineensis genome for characterization of their structural diversity, copy number and chromosomal distribution. Finally, their relative expression in several tissues was determined through in silico analysis of publicly available transcriptome data. Results: Our results reveal a congruence in the transpositional history of LTR retrotransposons between E. oleifera and E. guineensis, especially the Sto-4 family. Also, we have identified and described 583 full-length LTR-retrotransposons in the Elaeis guineensis genome. Our work shows that these elements are most likely no longer mobile and that no recent insertion event has occurred. Moreover, the analysis of chromosomal distribution suggests a preferential insertion of Copia elements in gene-rich regions, whereas Gypsy elements appear to be evenly distributed throughout the genome. Conclusions: Considering the high proportion of LTR retrotransposon in the oil palm genome, our work will contribute to a greater understanding of their impact on

Published
2015

19. A story of flasks and flowers: new perspectives in the search for markers of the mantled somaclonal variation of oil palm [W552]

Author

Jaligot, Estelle, Wei Yeng Hooi, Richaud, Frédérique, Agbessi, Mawussé D.T., Yen Yen Kwan, Beulé, Thierry, Collin, Myriam, Debladis, Emilie, Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Alwee, Sharifah Shahrul Rabiah Syed, Rival, Alain, Jaligot, Estelle, Wei Yeng Hooi, Richaud, Frédérique, Agbessi, Mawussé D.T., Yen Yen Kwan, Beulé, Thierry, Collin, Myriam, Debladis, Emilie, Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Alwee, Sharifah Shahrul Rabiah Syed, and Rival, Alain

Abstract

The mantled somaclonal variation of oil palm (Elaeis guineensis Jacq.) is morphologically similar to mutants defective in MADS-box genes of the B-class. Indeed in such mutants male floral organs are converted into female ones and this can be observed in oil palm flowers of both sexes. The detrimental consequences of somaclonal variation on fruit set then oil yields and its unpredictable incidence in clonal progenies have prompted the search for early detection markers. More generally, a better understanding of the molecular mechanisms underlying the onset and the maintenance of this variant phenotype is needed. The mantledsomaclonal variation is observed only in clonal populations generated through somatic embryogenesis at a large commercial stage. Thus, because of the nature of the variation, research strategy must involve two parallel approaches aimed at studying simultaneously the in vitro stages of clonal palms production (the flask) and the in plantadevelopment of the reproductive organs which are affected by the phenotype (the flower). On both materials a novel combination of epigenetics approaches, high-throughput sequencing technologies and bioinformatics analyses now provide new insights into a complex developmental phenomenon. Our research work also paves the way for innovation and development oriented towards end-users in the palm oil industry. (Texte intégral)

Published
2015

20. DNA methylation and expression of the EgDEF1 gene and neighboring retrotransposons in mantled somaclonal variants of oil palm

Author

Jaligot, Estelle, Wei Yeng Hooi, Debladis, Emilie, Richaud, Frédérique, Beulé, Thierry, Collin, Myriam, Agbessi, Mawussé D.T., Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Syed Alwee, Sharifah Shahrul Rabiah, Rival, Alain, Jaligot, Estelle, Wei Yeng Hooi, Debladis, Emilie, Richaud, Frédérique, Beulé, Thierry, Collin, Myriam, Agbessi, Mawussé D.T., Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Syed Alwee, Sharifah Shahrul Rabiah, and Rival, Alain

Abstract

The mantled floral phenotype of oil palm (Elaeis guineensis) affects somatic embryogenesis-derived individuals and is morphologically similar to mutants defective in the B-class MADS-box genes. This somaclonal variation has been previously demonstrated to be associated to a significant deficit in genome-wide DNA methylation. In order to elucidate the possible role of DNA methylation in the transcriptional regulation of EgDEF1, the APETALA3 ortholog of oil palm, we studied this epigenetic mark within the gene in parallel with transcript accumulation in both normal and mantled developing inflorescences. We also examined the methylation and expression of two neighboring retrotransposons that might interfere with EgDEF1 regulation. We show that the EgDEF1 gene is essentially unmethylated and that its methylation pattern does not change with the floral phenotype whereas expression is dramatically different, ruling out a direct implication of DNA methylation in the regulation of this gene. Also, we find that both the gypsy element inserted within an intron of the EgDEF1 gene and the copia element located upstream from the promoter are heavily methylated and show little or no expression. Interestingly, we identify a shorter, alternative transcript produced by EgDEF1 and characterize its accumulation with respect to its full-length counterpart. We demonstrate that, depending on the floral phenotype, the respective proportions of these two transcripts change differently during inflorescence development. We discuss the possible phenotypical consequences of this alternative splicing and the new questions it raises in the search for the molecular mechanisms underlying the mantled phenotype in the oil palm.

Published
2014

21. DNA methylation and expression of the EgDEF1 gene and neighboring retrotransposons in mantled somaclonal variants of oil palm

Author

Jaligot, Estelle, Wei Yeng Hooi, Debladis, Emilie, Richaud, Frédérique, Beulé, Thierry, Collin, Myriam, Agbessi, Mawussé D.T., Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Syed Alwee, Sharifah Shahrul Rabiah, Rival, Alain, Jaligot, Estelle, Wei Yeng Hooi, Debladis, Emilie, Richaud, Frédérique, Beulé, Thierry, Collin, Myriam, Agbessi, Mawussé D.T., Sabot, François, Garsmeur, Olivier, D'Hont, Angélique, Syed Alwee, Sharifah Shahrul Rabiah, and Rival, Alain

Abstract

The mantled floral phenotype of oil palm (Elaeis guineensis) affects somatic embryogenesis-derived individuals and is morphologically similar to mutants defective in the B-class MADS-box genes. This somaclonal variation has been previously demonstrated to be associated to a significant deficit in genome-wide DNA methylation. In order to elucidate the possible role of DNA methylation in the transcriptional regulation of EgDEF1, the APETALA3 ortholog of oil palm, we studied this epigenetic mark within the gene in parallel with transcript accumulation in both normal and mantled developing inflorescences. We also examined the methylation and expression of two neighboring retrotransposons that might interfere with EgDEF1 regulation. We show that the EgDEF1 gene is essentially unmethylated and that its methylation pattern does not change with the floral phenotype whereas expression is dramatically different, ruling out a direct implication of DNA methylation in the regulation of this gene. Also, we find that both the gypsy element inserted within an intron of the EgDEF1 gene and the copia element located upstream from the promoter are heavily methylated and show little or no expression. Interestingly, we identify a shorter, alternative transcript produced by EgDEF1 and characterize its accumulation with respect to its full-length counterpart. We demonstrate that, depending on the floral phenotype, the respective proportions of these two transcripts change differently during inflorescence development. We discuss the possible phenotypical consequences of this alternative splicing and the new questions it raises in the search for the molecular mechanisms underlying the mantled phenotype in the oil palm.

Published
2014

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