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1. A framework for conducting GWAS using repeated measures data with an application to childhood BMI

Author

Burrows, Kimberley, Heiskala, Anni, Bradfield, Jonathan P., Balkhiyarova, Zhanna, Ning, Lijiao, Boissel, Mathilde, Chan, Yee-Ming, Froguel, Philippe, Bonnefond, Amelie, Hakonarson, Hakon, Alves, Alexessander Couto, Lawlor, Deborah A., Kaakinen, Marika, Järvelin, Marjo-Riitta, Grant, Struan F. A., Tilling, Kate, Prokopenko, Inga, Sebert, Sylvain, Canouil, Mickaël, and Warrington, Nicole M.

Published
2024
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2. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Bradfeld, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithiof-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfeld, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.

Published
2024
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3. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkhiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Kindler, Joseph, Kähönen, Mika, Lanca, Carla, Lappe, Joan, Lee, Nanette R., McCormack, Shana, Mentch, Frank D., Mitchell, Jonathan A., Mononen, Nina, Niinikoski, Harri, Oken, Emily, Pahkala, Katja, Sim, Xueling, Teo, Yik-Ying, Baier, Leslie J., van Beijsterveldt, Toos, Adair, Linda S., Boomsma, Dorret I., de Geus, Eco, Guxens, Mònica, Eriksson, Johan G., Felix, Janine F., Gilliland, Frank D., Biobank, Penn Medicine, Hansen, Torben, Hardy, Rebecca, Hivert, Marie-France, Holm, Jens-Christian, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Lehtimäki, Terho, Mackey, David A., Meyre, David, Mohlke, Karen L., Mykkänen, Juha, Oberfield, Sharon, Pennell, Craig E., Perry, John R. B., Raitakari, Olli, Rivadeneira, Fernando, Saw, Seang-Mei, Sebert, Sylvain, Shepherd, John A., Standl, Marie, Sørensen, Thorkild I. A., Timpson, Nicholas J., Torrent, Maties, Willemsen, Gonneke, Hypponen, Elina, Power, Chris, McCarthy, Mark I., Freathy, Rachel M., Widén, Elisabeth, Hakonarson, Hakon, Prokopenko, Inga, Voight, Benjamin F., Zemel, Babette S., Grant, Struan F. A., and Cousminer, Diana L.

Published
2024
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4. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfeld, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithiof-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfeld, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Published
2024
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5. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfield, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithioff-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfield, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.

Published
2024
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6. POSITIVE, NEGATIVE, AND AMPLIFIED NETWORK EXTERNALITIES IN PLATFORM MARKETS.

Author

KARHU, KIMMO, HEISKALA, MIKKO, RITALA, PAAVO, and THOMAS, LLEWELLYN D. W.

Subjects
EXTERNALITIES, HETEROGENEITY, ACTORS
Abstract

Platforms are a dominant model for coordinating complex economic interactions. Platforms are distinguished by growth through network effects: an increase in the number (N) of platform actors (or complements produced by them) on one side makes the platform more valuable for an actor on the same or other side (and vice versa). This paper unbundles the network effect—the feedback loop—into directional and distinct types of network externalities that define the value received by each platform side. For example, value from a network externality may relate to variety (e.g., Google Play apps) or availability (e.g., Uber rides). Furthermore, at times, network externalities can have a negative impact. Although the existing literature recognizes some of these constituents, we lack an integrative framework. To address this gap, we first distinguish the heterogeneity and persistence of platform value units to identify a 2 × 2 typology of four positive and negative network externalities: quantity versus rivalry, accumulation versus fragmentation, variety versus choice overload, and utility versus degradation. Second, we generalize network connectivity and horizontal complementarity as two types of network externality amplification. Third, we demonstrate how all these dynamics play together in interactions that ultimately underscore the platformvalue and growth. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Openness and Open-Endedness: Implications for Mass Customization Capabilities

Author

Heiskala, Mikko, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Galizia, Francesco Gabriele, editor, and Bortolini, Marco, editor

Published
2023
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11. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

Author

Vehmeijer, Florianne OL, Küpers, Leanne K, Sharp, Gemma C, Salas, Lucas A, Lent, Samantha, Jima, Dereje D, Tindula, Gwen, Reese, Sarah, Qi, Cancan, Gruzieva, Olena, Page, Christian, Rezwan, Faisal I, Melton, Philip E, Nohr, Ellen, Escaramís, Geòrgia, Rzehak, Peter, Heiskala, Anni, Gong, Tong, Tuominen, Samuli T, Gao, Lu, Ross, Jason P, Starling, Anne P, Holloway, John W, Yousefi, Paul, Aasvang, Gunn Marit, Beilin, Lawrence J, Bergström, Anna, Binder, Elisabeth, Chatzi, Leda, Corpeleijn, Eva, Czamara, Darina, Eskenazi, Brenda, Ewart, Susan, Ferre, Natalia, Grote, Veit, Gruszfeld, Dariusz, Håberg, Siri E, Hoyo, Cathrine, Huen, Karen, Karlsson, Robert, Kull, Inger, Langhendries, Jean-Paul, Lepeule, Johanna, Magnus, Maria C, Maguire, Rachel L, Molloy, Peter L, Monnereau, Claire, Mori, Trevor A, Oken, Emily, Räikkönen, Katri, Rifas-Shiman, Sheryl, Ruiz-Arenas, Carlos, Sebert, Sylvain, Ullemar, Vilhelmina, Verduci, Elvira, Vonk, Judith M, Xu, Cheng-jian, Yang, Ivana V, Zhang, Hongmei, Zhang, Weiming, Karmaus, Wilfried, Dabelea, Dana, Muhlhausler, Beverly S, Breton, Carrie V, Lahti, Jari, Almqvist, Catarina, Jarvelin, Marjo-Riitta, Koletzko, Berthold, Vrijheid, Martine, Sørensen, Thorkild IA, Huang, Rae-Chi, Arshad, Syed Hasan, Nystad, Wenche, Melén, Erik, Koppelman, Gerard H, London, Stephanie J, Holland, Nina, Bustamante, Mariona, Murphy, Susan K, Hivert, Marie-France, Baccarelli, Andrea, Relton, Caroline L, Snieder, Harold, Jaddoe, Vincent WV, and Felix, Janine F

Subjects
Biological Sciences, Genetics, Pediatric, Nutrition, Prevention, Human Genome, Obesity, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Cardiovascular, Cancer, Stroke, Oral and gastrointestinal, Adolescent, Body Mass Index, Child, Child, Preschool, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Epigenome, Female, Fetal Blood, Humans, Male, Parturition, Pediatric Obesity, Pregnancy, Body mass index, Childhood obesity, DNA methylation, Epigenetics, Clinical Sciences
Abstract

BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P

Published
2020

28. Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

Author

Justiina Ronkainen, Anni Heiskala, Florianne O.L. Vehmeijer, Estelle Lowry, Doretta Caramaschi, Guadalupe Estrada Gutierrez, Jonathan A. Heiss, Nadine Hummel, Elina Keikkala, Tuomas Kvist, Allison Kupsco, Phillip E. Melton, Giancarlo Pesce, Munawar H. Soomro, Marta Vives-Usano, Nour Baiz, Elisabeth Binder, Darina Czamara, Mònica Guxens, Sanna Mustaniemi, Stephanie J. London, Sebastian Rauschert, Marja Vääräsmäki, Martine Vrijheid, Anette-G. Ziegler, Isabella Annesi-Maesano, Mariona Bustamante, Rae-Chi Huang, Sandra Hummel, Allan C. Just, Eero Kajantie, Jari Lahti, Deborah Lawlor, Katri Räikkönen, Marjo-Riitta Järvelin, Janine F. Felix, and Sylvain Sebert

Subjects
maternal haemoglobin, dna methylation, developmental programming, pregnancy, Genetics, QH426-470
Abstract

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.

Published
2022
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29. A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts

Author

Burrows, Kimberley, primary, Heiskala, Anni, additional, Bradfield, Jonathan P, additional, Balkhiyarova, Zhanna, additional, Ning, Lijiao, additional, Boissel, Mathilde, additional, Chan, Yee-Ming, additional, Froguel, Philippe, additional, Bonnefond, Amelie, additional, Hakonarson, Hakon, additional, Couto Alves, Alessander, additional, Lawlor, Deborah A, additional, Kaakinen, Marika, additional, Jarvelin, Marjo-Riitta, additional, Grant, Struan F.A., additional, Tilling, Kate, additional, Prokopenko, Inga, additional, Sebert, Sylvain, additional, Canouil, Mickael, additional, and Warrington, Nicole M, additional

Published
2024
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31. Educational tracking and social inequalities in long-term labor market outcomes:Six countries in comparison

Author

Schindler, Steffen, Bar-Haim, Yair, Barone, Carlo, Birkelund, Jesper Fels, Boliver, Vikki, Capsada-Munsech, Queralt, Erola, Jani, Facchini, Marta, Feniger, Yariv, Heiskala, Laura, Herbaut, Estelle, Ichou, ‪Mathieu, Karlson, Kristian Bernt, Kleinert, Corina, Reimer, David, Traini, Claudia, Triventi, Moris, Vallet, Louis-André, Schindler, Steffen, Bar-Haim, Yair, Barone, Carlo, Birkelund, Jesper Fels, Boliver, Vikki, Capsada-Munsech, Queralt, Erola, Jani, Facchini, Marta, Feniger, Yariv, Heiskala, Laura, Herbaut, Estelle, Ichou, ‪Mathieu, Karlson, Kristian Bernt, Kleinert, Corina, Reimer, David, Traini, Claudia, Triventi, Moris, and Vallet, Louis-André

Abstract

In this country-comparative study, we ask to what extent differentiation in secondary education accounts for the association between social origins and social destinations in adult age. We go beyond the widely applied formal definitions of educational tracking and particularly pay attention to country-specific approaches to educational differentiation. Our main expectation is that once we factor in these particularities, the degree to which educational differentiation accounts for social reproduction is quite similar across countries. Our analyses are based on national individual-level life-course data from six European countries that span from secondary education to occupational maturity. Our findings show that educational differentiation mediates the association between social origins and social destinations to a substantial degree in all countries. However, we still find some differences between countries in the extent to which educational differentiation accounts for social reproduction.

Published
2024

32. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Bradfield, Jonathan P, Kember, Rachel L, Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M, Bell, Joshua A, Broadaway, K Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M, Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M, Have, Christian Theil, Strachan, David P, Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H, Wang, Carol A, Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W James, Glessner, Joseph T, Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L, Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Hansen, Torben, Holm, Jens-Christian, Sørensen, Thorkild I A, Grant, Struan F A, Cousminer, Diana L, Bradfield, Jonathan P, Kember, Rachel L, Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M, Bell, Joshua A, Broadaway, K Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M, Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M, Have, Christian Theil, Strachan, David P, Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H, Wang, Carol A, Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W James, Glessner, Joseph T, Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L, Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Hansen, Torben, Holm, Jens-Christian, Sørensen, Thorkild I A, Grant, Struan F A, and Cousminer, Diana L

Abstract

Background: Pubertal growth patterns correlate with future health outcomes. How‑ever, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Transla‑tion And Rotation (SITAR) growth curve analysis on~56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analy‑ses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results: Large-scale growth modeling enables an unprecedented view of adoles‑ cent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide signifcant loci and leverage trans-ancestry data to perform fnemapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with diferent growth trajectories correlated with dif‑ferent outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fbrillation. Conclusion: We report novel genetic associations with the tempo of pubertal growth and fnd that genetic determinants of growth are correlated with reproductive, glyce‑mic, respiratory, and cardiac traits in adulthood. These results aid in identifying specifc growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern., BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank.RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation.CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Published
2024

38. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author

Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F., Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A., Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d’Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B., Jaddoe, Vincent W. V., Kaakinen, Marika A., Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F., Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R., Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M., Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, Sebert, Sylvain, Juola, Teija, Nedelec, Rozenn, Ronkainen, Justiina, Heiskala, Anni, Halonen, Miia, He, Yiyan, Miettunen, Jouko, Karhunen, Ville, Kajantie, Eero, Vääräsmäki, Marja, Keikkala, Elina, Nyberg, Pia, Serpi, Raisa, Felix, Janine, Jaddoe, Vincent, Marques, Irene, Moreira da Silva Santos, Susana, Kavousi, Maryam, Voortman, Trudy, Ginos, Bigina, Chadeau-Hyam, Marc, Järvelin, Marjo-Riitta, Tzala, Evangelia, De Toro, Nina, Wright, Thomas, Bodinier, Barbara, Dagnino, Sonia, Evans, Jayne, Webster, Claire, Kolehmainen, Marjukka, Hanhineva, Kati, Lakka, Timo, Savolainen, Otto, Zarei, Iman, Näätänen, Mari, Klåvus, Anton, Eloranta, Aino-Maija, Väistö, Juuso, Kårlund, Anna, Mikkonen, Santtu, Atalay, Merja, Atalay, Mustafa, Landberg, Rikard, Brunius, Carl, Ribbenstedt, Anton, Swertz, Morris, Hyde, Eleanor, Haakma, Sido, van Enckevort, Esther, Heude, Barbara, Charles, Marie-Aline, Zins, Marie, Lepeule, Johanna, Jacquemin, Bénédicte, Calas, Lucinda, Lequy-Flahault, Emeline, Lun Yuan, Wen, Seyve, Emie, Conti, Gabriella, Vermeulen, Roel, Hoek, Gerard, Kerckhoffs, Jules, Prokopenko, Inga, Kaakinen, Marika, Balkhiyarova, Zhanna, Ulrich, Anna, Roseboom, Tessa, De Rooij, Susanne, Motoc, Irina, Marie Ulven, Stine, Holven, Kirsten B., Matthews, Jason, Rundblad, Amanda, Das, Siddhartha, Timpson, Nicholas, Elhakeem, Ahmed, Luiza Goncalves Soares, Ana, Lekadir, Karim, Maria Cascarano, Anna, Maria Atehortua Labrador, Angélica, Ngoc Dang, Vien, Heil, Katharina F., Gallin, Catherine, Díaz, Oliver, Bulgheroni, Maria, Simonetti, Valentina, D’Amico, Enrico, Giani, Laura, Manzino, Fabrizio, Parusso, Stefano, Castleton, Christopher, Moimas, Diego, Atella, Vincenzo, Piano Mortari, Andrea, Kopinska, Joanna, Marazzi, Francesca, Giaccherini, Matilde, and Belotti, Federico

Published
2022
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39. Imaging affective and non-affective touch processing in two-year-old children

Author

Ambika Maria, Pauliina Hirvi, Kalle Kotilahti, Juha Heiskala, Jetro J. Tuulari, Linnea Karlsson, Hasse Karlsson, and Ilkka Nissilä

Subjects
Affective touch, Child, Development, Insula, Diffuse optical tomography, Optical properties, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Touch is an important component of early parent-child interaction and plays a critical role in the socio-emotional development of children. However, there are limited studies on touch processing amongst children in the age range from one to three years. The present study used frequency-domain diffuse optical tomography (DOT) to investigate the processing of affective and non-affective touch over left frontotemporal brain areas contralateral to the stimulated forearm in two-year-old children. Affective touch was administered by a single stroke with a soft brush over the child's right dorsal forearm at 3 cm/s, while non-affective touch was provided by multiple brush strokes at 30 cm/s. We found that in the insula, the total haemoglobin (HbT) response to slow brushing was significantly greater than the response to fast brushing (slow > fast). Additionally, a region in the postcentral gyrus, Rolandic operculum and superior temporal gyrus exhibited greater response to fast brushing than slow brushing (fast > slow). These findings confirm that an adult-like pattern of haemodynamic responses to affective and non-affective touch can be recorded in two-year-old subjects using DOT. To improve the accuracy of modelling light transport in the two-year-old subjects, we used a published age-appropriate atlas and deformed it to match the exterior shape of each subject's head. We estimated the combined scalp and skull, and grey matter (GM) optical properties by fitting simulated data to calibrated and coupling error corrected phase and amplitude measurements. By utilizing a two-compartment cerebrospinal fluid (CSF) model, the accuracy of estimation of GM optical properties and the localization of activation in the insula was improved. The techniques presented in this paper can be used to study neural development of children at different ages and illustrate that the technology is well-tolerated by most two-year-old children and not excessively sensitive to subject movement. The study points the way towards exciting possibilities in functional imaging of deeper functional areas near sulci in small children.

Published
2022
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42. Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

Author

Estelle Lowry, Nina Rautio, Niko Wasenius, Tom A. Bond, Jari Lahti, Ioanna Tzoulaki, Abbas Dehghan, Anni Heiskala, Leena Ala-Mursula, Jouko Miettunen, Johan Eriksson, Marjo-Riitta Järvelin, and Sylvain Sebert

Subjects
Early life, Social disadvantage, Body mass index (BMI), Maternal, Polygenic risk score for BMI, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI. Methods We studied participants of Helsinki Birth Cohort Study born in 1934–1944 (HBCS1934–1944, n = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n = 5807, NFBC1986, n = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934–1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex. Results The association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (β = 0.79, 95% CI, 0.33, 1.25, p

Published
2020
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46. The Extended Social Grid Model Revisited

Author

Ziegler, Rafael, primary, Nicholls, Alex, additional, Aro, Jari, additional, Beers, Cees van, additional, Chiappero-Martinetti, Enrica, additional, Edmiston, Daniel, additional, Havas, Attila, additional, Heiskala, Risto, additional, Jacobi, Nadia von, additional, Kubeczko, Klaus, additional, Linden, Martijn Jeroen van der, additional, Maestripieri, Lara, additional, Mildenberger, Georg, additional, Molnár, György, additional, and Schimpf, Gudrun-Christine, additional

Published
2019
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