Author: "Pahkala, K. (Katja)" - Searchworks@Jio Institute Digital Library Search Results

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1. The relationship between temperament, polygenic score for intelligence and cognition:a population-based study of middle-aged adults

Author: Tölli, P. (Pekka), Keltikangas-Järvinen, L. (Liisa), Lehtimäki, T. (Terho), Ravaja, N. (Niklas), Hintsanen, M. (Mirka), Ahola-Olli, A. (Ari), Pahkala, K. (Katja), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Laitinen, T. T. (Tomi T.), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Dobewall, H. (Henrik), Jokinen, E. (Eero), Raitakari, O. (Olli), Cloninger, C. R. (C. Robert), Rovio, S. (Suvi), Saarinen, A. (Aino), Tölli, P. (Pekka), Keltikangas-Järvinen, L. (Liisa), Lehtimäki, T. (Terho), Ravaja, N. (Niklas), Hintsanen, M. (Mirka), Ahola-Olli, A. (Ari), Pahkala, K. (Katja), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Laitinen, T. T. (Tomi T.), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Dobewall, H. (Henrik), Jokinen, E. (Eero), Raitakari, O. (Olli), Cloninger, C. R. (C. Robert), Rovio, S. (Suvi), and Saarinen, A. (Aino)
Abstract: We investigated whether temperament modifies an association between polygenic intelligence potential and cognitive test performance in midlife. The participants (n = 1647, born between 1962 and 1977) were derived from the Young Finns Study. Temperament was assessed with Temperament and Character Inventory over a 15-year follow-up (1997, 2001, 2007, 2012). Polygenic intelligence potential was assessed with a polygenic score for intelligence. Cognitive performance (visual memory, reaction time, sustained attention, spatial working memory) was assessed with CANTAB in midlife. The PGSI was significantly associated with the overall cognitive performance and performance in visual memory, sustained attention and working memory tests but not reaction time test. Temperament did not correlate with polygenic score for intelligence and did not modify an association between the polygenic score and cognitive performance, either. High persistence was associated with higher visual memory (B = 0.092; FDR-adj. p = 0.007) and low harm avoidance with higher overall cognitive performance, specifically better reaction time (B = −0.102; FDR-adj; p = 0.007). The subscales of harm avoidance had different associations with cognitive performance: higher “anticipatory worry,” higher “fatigability,” and lower “shyness with strangers” were associated with lower cognitive performance, while the role of “fear of uncertainty” was subtest-related. In conclusion, temperament does not help or hinder one from realizing their genetic potential for intelligence. The overall modest relationships between temperament and cognitive performance advise caution if utilizing temperament-related information e.g. in working-life recruitments. Cognitive abilities may be influenced by temperament variables, such as the drive for achievement and anxiety about test performance, but they involve distinct systems of learning and memory.
Published: 2022

2. Determining the timing of pubertal onset via a multicohort analysis of growth

Author: Syrjälä, E. (Essi), Niinikoski, H. (Harri), Virtanen, H. E. (Helena E.), Ilonen, J. (Jorma), Knip, M. (Mikael), Hutri-Kähönen, N. (Nina), Pahkala, K. (Katja), Raitakari, O. T. (Olli T.), Rodprasert, W. (Wiwat), Toppari, J. (Jorma), Virtanen, S. M. (Suvi M.), Veijola, R. (Riitta), Peltonen, J. (Jaakko), Nevalainen, J. (Jaakko), Tampere University, Health Sciences, Department of Paediatrics, Clinical Medicine, Pediatrics, Computing Sciences, HUS Children and Adolescents, Doctoral Programme in Clinical Research, Children's Hospital, and CAMM - Research Program for Clinical and Molecular Metabolism
Subjects: Male, Physiology, Growth, Adolescents, Cohort Studies, Families, Endocrinology, Medical Conditions, Risk Factors, 3123 Gynaecology and paediatrics, Medicine and Health Sciences, Breast, Age of Onset, Child, Children, 112 Statistics and probability, Finland, Biological Phenomena, Men, 3142 Public health care science, environmental and occupational health, Physiological Parameters, Research Design, Medicine, Female, Infants, Research Article, Childhood Obesity, Adolescent, Endocrine Disorders, Science, Research and Analysis Methods, Diabetes Mellitus, Humans, Women, Genitalia, Obesity, Endocrine Physiology, Puberty, Body Weight, Biology and Life Sciences, Models, Theoretical, Overweight, Body Height, 3141 Health care science, Age Groups, Metabolic Disorders, People and Places, Population Groupings, Forecasting
Abstract: Objective Growth-based determination of pubertal onset timing would be cheap and practical. We aimed to determine this timing based on pubertal growth markers. Secondary aims were to estimate the differences in growth between cohorts and identify the role of overweight in onset timing. Design This multicohort study includes data from three Finnish cohorts—the Type 1 Diabetes Prediction and Prevention (DIPP, N = 2,825) Study, the Special Turku Coronary Risk Factor Intervention Project (STRIP, N = 711), and the Boy cohort (N = 66). Children were monitored for growth and Tanner staging (except in DIPP). Methods The growth data were analyzed using a Super-Imposition by Translation And Rotation growth curve model, and pubertal onset analyses were run using a time-to-pubertal onset model. Results The time-to-pubertal onset model used age at peak height velocity (aPHV), peak height velocity (PHV), and overweight status as covariates, with interaction between aPHV and overweight status for girls, and succeeded in determining the onset timing. Cross-validation showed a good agreement (71.0% for girls, 77.0% for boys) between the observed and predicted onset timings. Children in STRIP were taller overall (girls: 1.7 [95% CI: 0.9, 2.5] cm, boys: 1.0 [0.3, 2.2] cm) and had higher PHV values (girls: 0.13 [0.02, 0.25] cm/year, boys: 0.35 [0.21, 0.49] cm/year) than those in DIPP. Boys in the Boy cohort were taller (2.3 [0.3, 4.2] cm) compared with DIPP. Overweight girls showed pubertal onset at 1.0 [0.7, 1.4] year earlier compared with other girls. In boys, there was no such difference. Conclusions The novel modeling approach provides an opportunity to evaluate the Tanner breast/genital stage–based pubertal onset timing in cohort studies including longitudinal data on growth but lacking pubertal follow-up.
Published: 2021

3. The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), Willer, C. J. (Cristen J.), Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), and Willer, C. J. (Cristen J.)
Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4‐23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.
Published: 2021

4. Evaluating the direct effects of childhood adiposity on adult systemic metabolism:a multivariable Mendelian randomization analysis

Author: Richardson, T. G. (Tom G), Mykkänen, J. (Juha), Pahkala, K. (Katja), Ala-Korpela, M. (Mika), Bell, J. A. (Joshua A), Taylor, K. (Kurt), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Raitakari, O. (Olli), Smith, G. D. (George Davey), Richardson, T. G. (Tom G), Mykkänen, J. (Juha), Pahkala, K. (Katja), Ala-Korpela, M. (Mika), Bell, J. A. (Joshua A), Taylor, K. (Kurt), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Raitakari, O. (Olli), and Smith, G. D. (George Davey)
Abstract: Background: Individuals who are obese in childhood have an elevated risk of disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independently of adult adiposity, is unclear. In this study, we have simultaneously evaluated the effects of childhood and adulthood body size on 123 systemic molecular biomarkers representing multiple metabolic pathways. Methods: Two-sample Mendelian randomization (MR) was conducted to estimate the causal effect of childhood body size on a total of 123 nuclear magnetic resonance-based metabolic markers using summary genome-wide association study (GWAS) data from up to 24 925 adults. Multivariable MR was then applied to evaluate the direct effects of childhood body size on these metabolic markers whilst accounting for adult body size. Further MR analyses were undertaken to estimate the potential mediating effects of these circulating metabolites on the risk of coronary artery disease (CAD) in adulthood using a sample of 60 801 cases and 123 504 controls. Results: Univariable analyses provided evidence that childhood body size has an effect on 42 of the 123 metabolic markers assessed (based on P < 4.07 × 10−4). However, the majority of these effects (35/42) substantially attenuated when accounting for adult body size using multivariable MR. We found little evidence that the biomarkers that were potentially influenced directly by childhood body size (leucine, isoleucine and tyrosine) mediate this effect onto adult disease risk. Very-low-density lipoprotein markers provided the strongest evidence of mediating the long-term effect of adiposity on CAD risk. Conclusions: Our findings suggest that childhood adiposity predominantly exerts its detrimental effect on adult systemic metabolism along a pathway that involves adulthood body size.
Published: 2021

5. Association between number of siblings and cardiovascular risk factors in childhood and in adulthood:the Cardiovascular Risk in Young Finns Study

Author: Pihlman, J. (Jukka), Magnussen, C. G. (Costan G.), Rovio, S. P. (Suvi P.), Pahkala, K. (Katja), Jokinen, E. (Eero), Laitinen, T. P. (Tomi P.), Hutri-Kähönen, N. (Nina), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Kähönen, M. (Mika), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Juonala, M. (Markus), Nuotio, J. (Joel), Pihlman, J. (Jukka), Magnussen, C. G. (Costan G.), Rovio, S. P. (Suvi P.), Pahkala, K. (Katja), Jokinen, E. (Eero), Laitinen, T. P. (Tomi P.), Hutri-Kähönen, N. (Nina), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Kähönen, M. (Mika), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Juonala, M. (Markus), and Nuotio, J. (Joel)
Abstract: Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3–18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m², 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m², 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m², 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention.
Published: 2021

6. Achievement of the targets of the 20-year infancy-onset dietary intervention:association with metabolic profile from childhood to adulthood

Author: Lehtovirta, M. (Miia), Matthews, L. A. (Laurie A.), Laitinen, T. T. (Tomi T.), Nuotio, J. (Joel), Niinikoski, H. (Harri), Rovio, S. P. (Suvi P.), Lagström, H. (Hanna), Viikari, J. S. (Jorma S. A.), Rönnemaa, T. (Tapani), Jula, A. (Antti), Ala-Korpela, M. (Mika), Raitakari, O. T. (Olli T.), Pahkala, K. (Katja), Lehtovirta, M. (Miia), Matthews, L. A. (Laurie A.), Laitinen, T. T. (Tomi T.), Nuotio, J. (Joel), Niinikoski, H. (Harri), Rovio, S. P. (Suvi P.), Lagström, H. (Hanna), Viikari, J. S. (Jorma S. A.), Rönnemaa, T. (Tapani), Jula, A. (Antti), Ala-Korpela, M. (Mika), Raitakari, O. T. (Olli T.), and Pahkala, K. (Katja)
Abstract: The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.
Published: 2021

7. Childhood Exposure to Parental Smoking and Midlife Cognitive Function The Young Finns Study

Author: Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, and Children's Hospital
Subjects: SECONDHAND SMOKE, parental smoking, passive smoking, NICOTINE EXPOSURE, Cambridge Neuropsychological Test Automated Battery, ADULTHOOD, PERFORMANCE, 3142 Public health care science, environmental and occupational health, COTININE, AGE, CIGARETTE-SMOKE, SELF-REPORTED SMOKING, CARDIOVASCULAR RISK-FACTORS, OXIDATIVE STRESS, tobacco smoke, cognitive function, secondhand smoke
Abstract: We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine
Published: 2020

8. Childhood socioeconomic disadvantage and risk of fatty liver in adulthood:the cardiovascular risk in young Finns study

Author: Laitinen, T. T. (Tomi T.), Vahtera, J. (Jussi), Pahkala, K. (Katja), Magnussen, C. G. (Costan G.), Nuotio, J. (Joel), Hutri-Kähönen, N. (Nina), Kivimäki, M. (Mika), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Tossavainen, P. (Päivi), Pentti, J. (Jaana), Viikari, J. S. (Jorma S.A.), Juonala, M. (Markus), and Raitakari, O. T. (Olli T.)
Abstract: Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3‐18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow‐up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents’ socioeconomic position and socioeconomic circumstances in participants’ residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow‐up (2011) at ages 34‐49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18‐1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09‐1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.
Published: 2020

9. Childhood exposure to parental smoking and midlife cognitive function:the Young Finns Study

Author: Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), and Raitakari, O. T. (Olli T.)
Abstract: We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine <1.0 ng/mL); 2) hygienic parental smoking (1–2 smoking parents, cotinine <1.0 ng/mL); and 3) nonhygienic parental smoking (1–2 smoking parents, cotinine ≥1.0 ng/mL). Analyses adjusted for sex, age, family socioeconomic status, polygenic risk score for cognitive function, adolescent/adult smoking, blood pressure, and serum total cholesterol level. Compared with the nonexposed, participants exposed to nonhygienic parental smoking were at higher risk of poor (lowest quartile) midlife episodic memory and associative learning (relative risk (RR) = 1.38, 95% confidence interval (CI): 1.08, 1.75), and a weak association was found for short-term and spatial working memory (RR = 1.25, 95% CI: 0.98, 1.58). Associations for those exposed to hygienic parental smoking were nonsignificant (episodic memory and associative learning: RR = 1.19, 95% CI: 0.92, 1.54; short-term and spatial working memory: RR = 1.10, 95% CI: 0.85, 1.34). We conclude that avoiding childhood/adolescence secondhand smoke exposure promotes adulthood cognitive function.
Published: 2020

10. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author: Vogelezang, S. (Suzanne), Bradfield, J. P. (Jonathan P.), Ahluwalia, T. S. (Tarunveer S.), Curtin, J. A. (John A.), Lakka, T. A. (Timo A.), Grarup, N. (Niels), Scholz, M. (Markus), van der Most, P. J. (Peter J.), Monnereau, C. (Claire), Stergiakouli, E. (Evie), Heiskala, A. (Anni), Horikoshi, M. (Momoko), Fedko, I. O. (Iryna O.), Vilor-Tejedor, N. (Natalia), Cousminer, D. L. (Diana L.), Standl, M. (Marie), Wang, C. A. (Carol A.), Viikari, J. (Jorma), Geller, F. (Frank), iniguez, C. (Carmen), Pitkanen, N. (Niina), Chesi, A. (Alessandra), Bacelis, J. (Jonas), Yengo, L. (Loic), Torrent, M. (Maties), Ntalla, I. (Ioanna), Helgeland, O. (Oyvind), Selzam, S. (Saskia), Vonk, J. M. (Judith M.), Zafarmand, M. H. (Mohammed H.), Heude, B. (Barbara), Farooqi, I. S. (Ismaa Sadaf), Alyass, A. (Akram), Beaumont, R. N. (Robin N.), Have, C. T. (Christian T.), Rzehak, P. (Peter), Bilbao, J. R. (Jose Ramon), Schnurr, T. M. (Theresia M.), Barroso, I. (Ines), Bonnelykke, K. (Klaus), Beilin, L. J. (Lawrence J.), Carstensen, L. (Lisbeth), Charles, M.-A. (Marie-Aline), Chawes, B. (Bo), Clement, K. (Karine), Closa-Monasterolo, R. (Ricardo), Custovic, A. (Adnan), Eriksson, J. G. (Johan G.), Escribano, J. (Joaquin), Groen-Blokhuis, M. (Maria), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Hakonarson, H. (Hakon), Hansen, T. (Torben), Hattersley, A. T. (Andrew T.), Hollensted, M. (Mette), Hottenga, J.-J. (Jouke-Jan), Hypponen, E. (Elina), Johansson, S. (Stefan), Joro, R. (Raimo), Kahonen, M. (Mika), Karhunen, V. (Ville), Kiess, W. (Wieland), Knight, B. A. (Bridget A.), Koletzko, B. (Berthold), Kuehnapfel, A. (Andreas), Landgraf, K. (Kathrin), Langhendries, J.-P. (Jean-Paul), Lehtimaki, T. (Terho), Leinonen, J. T. (Jaakko T.), Li, A. (Aihuali), Lindi, V. (Virpi), Lowry, E. (Estelle), Bustamante, M. (Mariona), Medina-Gomez, C. (Carolina), Melbye, M. (Mads), Michaelsen, K. F. (Kim F.), Morgen, C. S. (Camilla S.), Mori, T. A. (Trevor A.), Nielsen, T. R. (Tenna R. H.), Niinikoski, H. (Harri), Oldehinkel, A. J. (Albertine J.), Pahkala, K. (Katja), Panoutsopoulou, K. (Kalliope), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Power, C. (Christine), Reijneveld, S. A. (Sijmen A.), Rivadeneira, F. (Fernando), Simpson, A. (Angela), Sly, P. D. (Peter D.), Stokholm, J. (Jakob), Teo, K. K. (Kook K.), Thiering, E. (Elisabeth), Timpson, N. J. (Nicholas J.), Uitterlinden, A. G. (Andre G.), van Beijsterveldt, C. E. (Catharina E. M.), van Schaik, B. D. (Barbera D. C.), Vaudel, M. (Marc), Verduci, E. (Elvira), Vinding, R. K. (Rebecca K.), Vogel, M. (Mandy), Zeggini, E. (Eleftheria), Sebert, S. (Sylvain), Lind, M. V. (Mads V.), Brown, C. D. (Christopher D.), Santa-Marina, L. (Loreto), Reischl, E. (Eva), Frithioff-Bojsoe, C. (Christine), Meyre, D. (David), Wheeler, E. (Eleanor), Ong, K. (Ken), Nohr, E. A. (Ellen A.), Vrijkotte, T. G. (Tanja G. M.), Koppelman, G. H. (Gerard H.), Plomin, R. (Robert), Njolstad, P. R. (Pal R.), Dedoussis, G. D. (George D.), Froguel, P. (Philippe), Sorensen, T. I. (Thorkild I. A.), Jacobsson, B. (Bo), Freathy, R. M. (Rachel M.), Zemel, B. S. (Babette S.), Raitakari, O. (Olli), Vrijheid, M. (Martine), Feenstra, B. (Bjarke), Lyytikainen, L.-P. (Leo-Pekka), Snieder, H. (Harold), Kirsten, H. (Holger), Holt, P. G. (Patrick G.), Heinrich, J. (Joachim), Widen, E. (Elisabeth), Sunyer, J. (Jordi), Boomsma, D. I. (Dorret I.), Jarvelin, M.-R. (Marjo-Riitta), Koerner, A. (Antje), Davey Smith, G. (George), Holm, J.-C. (Jens-Christian), Atalay, M. (Mustafa), Murray, C. (Clare), Bisgaard, H. (Hans), McCarthy, M. I. (Mark I.), Jaddoe, V. W. (Vincent W. V.), Grant, S. F. (Struan F. A.), Felix, J. F. (Janine F.), Vogelezang, S. (Suzanne), Bradfield, J. P. (Jonathan P.), Ahluwalia, T. S. (Tarunveer S.), Curtin, J. A. (John A.), Lakka, T. A. (Timo A.), Grarup, N. (Niels), Scholz, M. (Markus), van der Most, P. J. (Peter J.), Monnereau, C. (Claire), Stergiakouli, E. (Evie), Heiskala, A. (Anni), Horikoshi, M. (Momoko), Fedko, I. O. (Iryna O.), Vilor-Tejedor, N. (Natalia), Cousminer, D. L. (Diana L.), Standl, M. (Marie), Wang, C. A. (Carol A.), Viikari, J. (Jorma), Geller, F. (Frank), iniguez, C. (Carmen), Pitkanen, N. (Niina), Chesi, A. (Alessandra), Bacelis, J. (Jonas), Yengo, L. (Loic), Torrent, M. (Maties), Ntalla, I. (Ioanna), Helgeland, O. (Oyvind), Selzam, S. (Saskia), Vonk, J. M. (Judith M.), Zafarmand, M. H. (Mohammed H.), Heude, B. (Barbara), Farooqi, I. S. (Ismaa Sadaf), Alyass, A. (Akram), Beaumont, R. N. (Robin N.), Have, C. T. (Christian T.), Rzehak, P. (Peter), Bilbao, J. R. (Jose Ramon), Schnurr, T. M. (Theresia M.), Barroso, I. (Ines), Bonnelykke, K. (Klaus), Beilin, L. J. (Lawrence J.), Carstensen, L. (Lisbeth), Charles, M.-A. (Marie-Aline), Chawes, B. (Bo), Clement, K. (Karine), Closa-Monasterolo, R. (Ricardo), Custovic, A. (Adnan), Eriksson, J. G. (Johan G.), Escribano, J. (Joaquin), Groen-Blokhuis, M. (Maria), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Hakonarson, H. (Hakon), Hansen, T. (Torben), Hattersley, A. T. (Andrew T.), Hollensted, M. (Mette), Hottenga, J.-J. (Jouke-Jan), Hypponen, E. (Elina), Johansson, S. (Stefan), Joro, R. (Raimo), Kahonen, M. (Mika), Karhunen, V. (Ville), Kiess, W. (Wieland), Knight, B. A. (Bridget A.), Koletzko, B. (Berthold), Kuehnapfel, A. (Andreas), Landgraf, K. (Kathrin), Langhendries, J.-P. (Jean-Paul), Lehtimaki, T. (Terho), Leinonen, J. T. (Jaakko T.), Li, A. (Aihuali), Lindi, V. (Virpi), Lowry, E. (Estelle), Bustamante, M. (Mariona), Medina-Gomez, C. (Carolina), Melbye, M. (Mads), Michaelsen, K. F. (Kim F.), Morgen, C. S. (Camilla S.), Mori, T. A. (Trevor A.), Nielsen, T. R. (Tenna R. H.), Niinikoski, H. (Harri), Oldehinkel, A. J. (Albertine J.), Pahkala, K. (Katja), Panoutsopoulou, K. (Kalliope), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Power, C. (Christine), Reijneveld, S. A. (Sijmen A.), Rivadeneira, F. (Fernando), Simpson, A. (Angela), Sly, P. D. (Peter D.), Stokholm, J. (Jakob), Teo, K. K. (Kook K.), Thiering, E. (Elisabeth), Timpson, N. J. (Nicholas J.), Uitterlinden, A. G. (Andre G.), van Beijsterveldt, C. E. (Catharina E. M.), van Schaik, B. D. (Barbera D. C.), Vaudel, M. (Marc), Verduci, E. (Elvira), Vinding, R. K. (Rebecca K.), Vogel, M. (Mandy), Zeggini, E. (Eleftheria), Sebert, S. (Sylvain), Lind, M. V. (Mads V.), Brown, C. D. (Christopher D.), Santa-Marina, L. (Loreto), Reischl, E. (Eva), Frithioff-Bojsoe, C. (Christine), Meyre, D. (David), Wheeler, E. (Eleanor), Ong, K. (Ken), Nohr, E. A. (Ellen A.), Vrijkotte, T. G. (Tanja G. M.), Koppelman, G. H. (Gerard H.), Plomin, R. (Robert), Njolstad, P. R. (Pal R.), Dedoussis, G. D. (George D.), Froguel, P. (Philippe), Sorensen, T. I. (Thorkild I. A.), Jacobsson, B. (Bo), Freathy, R. M. (Rachel M.), Zemel, B. S. (Babette S.), Raitakari, O. (Olli), Vrijheid, M. (Martine), Feenstra, B. (Bjarke), Lyytikainen, L.-P. (Leo-Pekka), Snieder, H. (Harold), Kirsten, H. (Holger), Holt, P. G. (Patrick G.), Heinrich, J. (Joachim), Widen, E. (Elisabeth), Sunyer, J. (Jordi), Boomsma, D. I. (Dorret I.), Jarvelin, M.-R. (Marjo-Riitta), Koerner, A. (Antje), Davey Smith, G. (George), Holm, J.-C. (Jens-Christian), Atalay, M. (Mustafa), Murray, C. (Clare), Bisgaard, H. (Hans), McCarthy, M. I. (Mark I.), Jaddoe, V. W. (Vincent W. V.), Grant, S. F. (Struan F. A.), and Felix, J. F. (Janine F.)
Abstract: The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
Published: 2020

11. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Author: Liu, X. (Xueping), Helenius, D. (Dorte), Skotte, L. (Line), Beaumont, R. N. (Robin N.), Wielscher, M. (Matthias), Geller, F. (Frank), Juodakis, J. (Julius), Mahajan, A. (Anubha), Bradfield, J. P. (Jonathan P.), Lin, F. T. (Frederick Tj), Vogelezang, S. (Suzanne), Bustamante, M. (Mariona), Ahluwalia, T. S. (Tarunveer S.), Pitkanen, N. (Niina), Wang, C. A. (Carol A.), Bacelis, J. (Jonas), Borges, M. C. (Maria C.), Zhang, G. (Ge), Bedell, B. A. (Bruce A.), Rossi, R. M. (Robert M.), Skogstrand, K. (Kristin), Peng, S. (Shouneng), Thompson, W. K. (Wesley K.), Appadurai, V. (Vivek), Lawlor, D. A. (Debbie A.), Kalliala, I. (Ilkka), Power, C. (Christine), McCarthy, M. I. (Mark, I), Boyd, H. A. (Heather A.), Marazita, M. L. (Mary L.), Hakonarson, H. (Hakon), Hayes, M. G. (M. Geoffrey), Scholtens, D. M. (Denise M.), Rivadeneira, F. (Fernando), Jaddoe, V. W. (Vincent W. V.), Vinding, R. K. (Rebecca K.), Bisgaard, H. (Hans), Knight, B. A. (Bridget A.), Pahkala, K. (Katja), Raitakari, O. (Olli), Helgeland, O. (Oyvind), Johansson, S. (Stefan), Njolstad, P. R. (Pal R.), Fadista, J. (Joao), Schork, A. J. (Andrew J.), Nudel, R. (Ron), Miller, D. E. (Daniel E.), Chen, X. (Xiaoting), Weirauch, M. T. (Matthew T.), Mortensen, P. B. (Preben Bo), Borglum, A. D. (Anders D.), Nordentoft, M. (Merete), Mors, O. (Ole), Hao, K. (Ke), Ryckman, K. K. (Kelli K.), Hougaard, D. M. (David M.), Kottyan, L. C. (Leah C.), Pennell, C. E. (Craig E.), Lyytikainen, L.-P. (Leo-Pekka), Bonnelykke, K. (Klaus), Vrijheid, M. (Martine), Felix, J. F. (Janine F.), Lowe, W. L. (William L., Jr.), Grant, S. F. (Struan Fa), Hypponen, E. (Elina), Jacobsson, B. (Bo), Järvelin, M.-R. (Marjo-Riitta), Muglia, L. J. (Louis J.), Murray, J. C. (Jeffrey C.), Freathy, R. M. (Rachel M.), Werge, T. M. (Thomas M.), Melbye, M. (Mads), Buil, A. (Alfonso), Feenstra, B. (Bjarke), Liu, X. (Xueping), Helenius, D. (Dorte), Skotte, L. (Line), Beaumont, R. N. (Robin N.), Wielscher, M. (Matthias), Geller, F. (Frank), Juodakis, J. (Julius), Mahajan, A. (Anubha), Bradfield, J. P. (Jonathan P.), Lin, F. T. (Frederick Tj), Vogelezang, S. (Suzanne), Bustamante, M. (Mariona), Ahluwalia, T. S. (Tarunveer S.), Pitkanen, N. (Niina), Wang, C. A. (Carol A.), Bacelis, J. (Jonas), Borges, M. C. (Maria C.), Zhang, G. (Ge), Bedell, B. A. (Bruce A.), Rossi, R. M. (Robert M.), Skogstrand, K. (Kristin), Peng, S. (Shouneng), Thompson, W. K. (Wesley K.), Appadurai, V. (Vivek), Lawlor, D. A. (Debbie A.), Kalliala, I. (Ilkka), Power, C. (Christine), McCarthy, M. I. (Mark, I), Boyd, H. A. (Heather A.), Marazita, M. L. (Mary L.), Hakonarson, H. (Hakon), Hayes, M. G. (M. Geoffrey), Scholtens, D. M. (Denise M.), Rivadeneira, F. (Fernando), Jaddoe, V. W. (Vincent W. V.), Vinding, R. K. (Rebecca K.), Bisgaard, H. (Hans), Knight, B. A. (Bridget A.), Pahkala, K. (Katja), Raitakari, O. (Olli), Helgeland, O. (Oyvind), Johansson, S. (Stefan), Njolstad, P. R. (Pal R.), Fadista, J. (Joao), Schork, A. J. (Andrew J.), Nudel, R. (Ron), Miller, D. E. (Daniel E.), Chen, X. (Xiaoting), Weirauch, M. T. (Matthew T.), Mortensen, P. B. (Preben Bo), Borglum, A. D. (Anders D.), Nordentoft, M. (Merete), Mors, O. (Ole), Hao, K. (Ke), Ryckman, K. K. (Kelli K.), Hougaard, D. M. (David M.), Kottyan, L. C. (Leah C.), Pennell, C. E. (Craig E.), Lyytikainen, L.-P. (Leo-Pekka), Bonnelykke, K. (Klaus), Vrijheid, M. (Martine), Felix, J. F. (Janine F.), Lowe, W. L. (William L., Jr.), Grant, S. F. (Struan Fa), Hypponen, E. (Elina), Jacobsson, B. (Bo), Järvelin, M.-R. (Marjo-Riitta), Muglia, L. J. (Louis J.), Murray, J. C. (Jeffrey C.), Freathy, R. M. (Rachel M.), Werge, T. M. (Thomas M.), Melbye, M. (Mads), Buil, A. (Alfonso), and Feenstra, B. (Bjarke)
Abstract: The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
Published: 2019

12. Maternal and fetal genetic contribution to gestational weight gain

Author: Warrington, N.M. (N. M.), Richmond, R.C. (Rebecca C.), Fenstra, B. (B.), Myhre, R. (Ronny), Gaillard, R. (Romy), Paternoster, L. (L.), Wang, C.A. (C. A.), Beaumont, R.N. (R. N.), Das, S. (Shikta), Murcia, M. (Mario), Barton, S.J. (Sheila), Espinosa, A. (A.), Thiering, E. (Elisabeth), Atalay, M. (Mustafa), Pitkanen, N. (Niina), Ntalla, I. (Ioanna), Jonsson, A.E. (A. E.), Freathy, R.M. (Rachel), Karhunen, V. (V.), Tiesler, C.M.T. (C. M.T.), Allard, C. (Catherine), Crawford, A. (A.), Ring, S.M. (Susan), Melbye, M. (Mads), Magnus, P. (Per), Rivadeneira, F. (F.), Skotte, L. (L.), Hansen, T. (Torben), Marsh, J.A. (Julie), Guxens Junyent, M. (Mònica), Holloway, J.W. (J. W.), Grallert, H. (Harald), Jaddoe, V.W.V. (Vincent), Lowe, W.L. (W. L.), Roumeliotaki, T. (Theano), Hattersley, A.T. (Andrew), Lindi, V. (Virpi), Pahkala, K. (Katja), Panoutsopoulou, K. (K.), Standl, M. (M.), Flexeder, C. (Claudia), Bouchard, L. (Luigi), Aagaard Nohr, E. (E.), Santa-Marina, L. (Loreto), Kogevinas, M. (Manolis), Niinikoski, H. (H.), Dedoussis, G.V. (George), Heinrich, J. (J.), Reynolds, R.M. (Rebecca), Lakka, T.A. (Timo), Zeggini, E. (Eleftheria), Raitakari, O.T. (O. T.), Chatzi, L. (Leda), Inskip, H.M. (Hazel), Bustamante, M. (Mariona), Hivert, M.-F. (Marie-France), Jarvelin, M.-R. (M. R.), Sørensen, T.I.A. (Thorkild), Pennell, C.E. (Craig), Felix, J.F. (J. F.), Jacobsson, B. (B.), Geller, F. (Frank), Evans, D.M. (D. M.), Lawlor, D.A. (D. A.), Warrington, N.M. (N. M.), Richmond, R.C. (Rebecca C.), Fenstra, B. (B.), Myhre, R. (Ronny), Gaillard, R. (Romy), Paternoster, L. (L.), Wang, C.A. (C. A.), Beaumont, R.N. (R. N.), Das, S. (Shikta), Murcia, M. (Mario), Barton, S.J. (Sheila), Espinosa, A. (A.), Thiering, E. (Elisabeth), Atalay, M. (Mustafa), Pitkanen, N. (Niina), Ntalla, I. (Ioanna), Jonsson, A.E. (A. E.), Freathy, R.M. (Rachel), Karhunen, V. (V.), Tiesler, C.M.T. (C. M.T.), Allard, C. (Catherine), Crawford, A. (A.), Ring, S.M. (Susan), Melbye, M. (Mads), Magnus, P. (Per), Rivadeneira, F. (F.), Skotte, L. (L.), Hansen, T. (Torben), Marsh, J.A. (Julie), Guxens Junyent, M. (Mònica), Holloway, J.W. (J. W.), Grallert, H. (Harald), Jaddoe, V.W.V. (Vincent), Lowe, W.L. (W. L.), Roumeliotaki, T. (Theano), Hattersley, A.T. (Andrew), Lindi, V. (Virpi), Pahkala, K. (Katja), Panoutsopoulou, K. (K.), Standl, M. (M.), Flexeder, C. (Claudia), Bouchard, L. (Luigi), Aagaard Nohr, E. (E.), Santa-Marina, L. (Loreto), Kogevinas, M. (Manolis), Niinikoski, H. (H.), Dedoussis, G.V. (George), Heinrich, J. (J.), Reynolds, R.M. (Rebecca), Lakka, T.A. (Timo), Zeggini, E. (Eleftheria), Raitakari, O.T. (O. T.), Chatzi, L. (Leda), Inskip, H.M. (Hazel), Bustamante, M. (Mariona), Hivert, M.-F. (Marie-France), Jarvelin, M.-R. (M. R.), Sørensen, T.I.A. (Thorkild), Pennell, C.E. (Craig), Felix, J.F. (J. F.), Jacobsson, B. (B.), Geller, F. (Frank), Evans, D.M. (D. M.), and Lawlor, D.A. (D. A.)
Abstract: Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 â '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outc
Published: 2018
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13. Effect of dietary counseling on a comprehensive metabolic profile from childhood to adulthood

Author: Lehtovirta, M. (Miia), Pahkala, K. (Katja), Niinikoski, H. (Harri), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), Lagström, H. (Hanna), Viikari, J. S. (Jorma S. A.), Rönnemaa, T. (Tapani), Jula, A. (Antti), Ala-Korpela, M. (Mika), Würtz, P. (Peter), Raitakari, O. T. (Olli T.), Lehtovirta, M. (Miia), Pahkala, K. (Katja), Niinikoski, H. (Harri), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), Lagström, H. (Hanna), Viikari, J. S. (Jorma S. A.), Rönnemaa, T. (Tapani), Jula, A. (Antti), Ala-Korpela, M. (Mika), Würtz, P. (Peter), and Raitakari, O. T. (Olli T.)
Abstract: Objectives: To study the effects of repeated, infancy-onset dietary counseling on a detailed metabolic profile. Effects of dietary saturated fat replacement on circulating concentrations of metabolic biomarkers still remain unknown. Study design: The Special Turku Coronary Risk Factor Intervention Project (STRIP) study is a longitudinal, randomized atherosclerosis prevention trial in which repeated dietary counseling aimed at reducing the proportion of saturated fat intake. Nuclear magnetic resonance metabolomics quantified circulating metabolites from serum samples assessed at age 9 (n = 554), 11 (n = 553), 13 (n = 508), 15 (n = 517), 17 (n = 457), and 19 (n = 417) years. Results: The intervention reduced dietary intake of saturated fat (mean difference in daily percentage of total energy intake: −2.1 [95% CI −1.9 to −2.3]) and increased intake of polyunsaturated fat (0.6 [0.5–0.7]). The dietary counseling intervention led to greater serum proportions of polyunsaturated fatty acids (P < .001), with greater proportions of both circulating omega-3 (P = .02) and omega-6 (P < .001) fatty acids. The proportion of saturated fatty acids in serum was lower for both boys and girls in the intervention group (P < .001), whereas the serum proportion of monounsaturated fat was lower for boys in the intervention group only (P < .001). The intervention also reduced circulating intermediate-density lipoprotein and low-density lipoprotein lipid concentrations (P < .01). Dietary intervention effects on nonlipid biomarkers were minor except from greater concentrations of glutamine in the intervention group. Conclusions: Repeated dietary counseling from infancy to early adulthood yielded favorable effects on multiple circulating fatty acids and lipoprotein subclass lipids, particularly in boys. These molecular effects substantiate the beneficial role of saturated fat replacement on the metabolic risk profile.
Published: 2018

14. Genome-wide associations for birth weight and correlations with adult disease

Author: Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), Freathy, R.M. (Rachel), Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), and Freathy, R.M. (Rachel)
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg =-0.22, P = 5.5 × 10-13), T2D (Rg =-0.27, P = 1.1 × 10-6) and coronary artery disease (Rg =-0.30, P = 6.5 × 10-9). In addition, using large-cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.
Published: 2016
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15. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Author: Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), Kelly, A. (Andrea), Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), and Kelly, A. (Andrea)
Abstract: A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10-8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in streng
Published: 2016
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15 results on '"Pahkala, K. (Katja)"'

1. The relationship between temperament, polygenic score for intelligence and cognition:a population-based study of middle-aged adults

2. Determining the timing of pubertal onset via a multicohort analysis of growth

3. The power of genetic diversity in genome-wide association studies of lipids

4. Evaluating the direct effects of childhood adiposity on adult systemic metabolism:a multivariable Mendelian randomization analysis

5. Association between number of siblings and cardiovascular risk factors in childhood and in adulthood:the Cardiovascular Risk in Young Finns Study

6. Achievement of the targets of the 20-year infancy-onset dietary intervention:association with metabolic profile from childhood to adulthood

7. Childhood Exposure to Parental Smoking and Midlife Cognitive Function The Young Finns Study

8. Childhood socioeconomic disadvantage and risk of fatty liver in adulthood:the cardiovascular risk in young Finns study

9. Childhood exposure to parental smoking and midlife cognitive function:the Young Finns Study

10. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

11. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

12. Maternal and fetal genetic contribution to gestational weight gain

13. Effect of dietary counseling on a comprehensive metabolic profile from childhood to adulthood

14. Genome-wide associations for birth weight and correlations with adult disease

15. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

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