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1. Is geographical distance a barrier in the use of public primary health services among rural and urban young adults? Experience from Northern Finland

Author: Lankila, T., Näyhä, S., Rautio, A., Rusanen, J., Taanila, A., and Koiranen, M.
Published: 2016
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2. A natural history of erectile dysfunction in elderly men:a population-based, twelve-year prospective study

Author: Saramies, J. (Jouko), Koiranen, M. (Markku), Auvinen, J. (Juha), Uusitalo, H. (Hannu), Hussi, E. (Esko), Becker, S. (Sebastian), Keinänen-Kiukaanniemi, S. (Sirkka), Tuomilehto, J. (Jaakko), Suija, K. (Kadri), Saramies, J. (Jouko), Koiranen, M. (Markku), Auvinen, J. (Juha), Uusitalo, H. (Hannu), Hussi, E. (Esko), Becker, S. (Sebastian), Keinänen-Kiukaanniemi, S. (Sirkka), Tuomilehto, J. (Jaakko), and Suija, K. (Kadri)
Abstract: There is a wide variation in the development and course of erectile dysfunction (ED) in men, which confirms the need for prospective studies. We conducted a cross-sectional analysis among the general male population at the baseline (n = 359) and in a follow-up survey (n = 218) 12 years later. The prospective 12-year study included 189 men. ED was assessed using the International Index of Erectile Function questionnaire. The mean age of the participants was 62.0 years at the baseline, while at the 12-year follow-up it was 71.6 years. The crude prevalence of ED was 61.6% at the baseline and 78.9% at the follow-up, and the prevalence tended to increase with age. All of the men aged 75 years or more had at least mild ED. The incidence of ED in every thousand person years was 53.5. A total of 54.5% of the men experienced ED progression, while 39.2% reported no changes in erectile function, and 6.3% experienced ED regression during the 12-year study. The likelihood of ED progression was higher in the older compared with younger age group (odds ratio, OR 5.2 (95% CI: 1.1–26.2)), and the likelihood of ED regression was lower among men with increased depression symptoms (OR 0.3 (95% CI: 0.1–0.6)) and among men with a decreased interest in their sexual life (OR 0.1 (95% CI: 0.0–0.6)). Lifestyle factors such as the consumption of alcohol and smoking were not significantly associated with ED.
Published: 2022

3. How Do Persons with Intellectual Disability Manage in the Open Labour Markets? A Follow-Up of the Northern Finland 1966 Birth Cohort

Author: Taanila, A., Rantakallio, P., and Koiranen, M.
Abstract: The aim was to study how many of the individuals with intellectual disability (ID; IQ70) in an age cohort were not receiving a disability pension by the age of 34 years and what their life situation was like in terms of employment, education and morbidity. In 2000, the Northern Finland 1966 Birth Cohort (n=12058 live-born) included 129 individuals with ID. The outcome data on employment, education, pensions and morbidity were obtained from national registers. A total of 85.3% (n110) of all the individuals with ID were on pension, and 66 of them had severe ID (IQ<50) and 44 had mild ID (IQ 50-70). Altogether 99 were drawing a pension because of ID, and 11 had a main diagnosis other than ID in the register of Social Insurance Institution. Nineteen individuals with mild ID were not on disability pension. The educational level of those without pension was low, and all whose occupation was known worked in low-level manual trades in the open labour market. During the past 8 years (1993-2000), their employment rate had been lower and unemployment rate correspondingly higher and unemployment periods longer than those of the reference group (IQ>85 or not measured). As to the morbidity, they had been hospitalized twice more often than those in the reference group and the mean of their hospitalization days was over fourfold. More attention should be paid to the vocational education and supported employment services of individuals with ID to help them to manage as independently as possible.
Published: 2005
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4. 22-year trends in dysglycemia and body mass index:a population-based cohort study in Savitaipale, Finland

Author: Saramies, J. (Jouko), Koiranen, M. (Markku), Auvinen, J. (Juha), Uusitalo, H. (Hannu), Hussi, E. (Esko), Cederberg, H. (Henna), Keinänen-Kiukaanniemi, S. (Sirkka), Tuomilehto, J. (Jaakko), Saramies, J. (Jouko), Koiranen, M. (Markku), Auvinen, J. (Juha), Uusitalo, H. (Hannu), Hussi, E. (Esko), Cederberg, H. (Henna), Keinänen-Kiukaanniemi, S. (Sirkka), and Tuomilehto, J. (Jaakko)
Abstract: Aims: We describe a 22-year prospective observational population-based study that determined the prevalence and incidence of type 2 diabetes (T2D) and intermediate hyperglycaemia (IH), obesity, hypertension, and disorders of lipid metabolism in a middle-age population in the Finnish municipality of Savitaipale. Methods: 1151 people participated in the baseline survey in 1996–1999, following two follow-up examinations, in 2007–2008 and 2018−2019. Follow-up studies comprised clinical measurements, 2-h oral glucose tolerance test and other biochemistry, questionnaires, and registry data. Results: The prevalence of T2D quadrupled to 27% and the proportion of normoglycemic people decreased from 73% to 44% while IH increased only slightly during the 22-year follow-up. A large proportion of people who died between the surveys were diabetic. The mean body mass index (BMI) did not, whereas mean waist circumference increased significantly, by 5−6 cm (P = 0.001) during the 22 years. Systolic blood pressure increased by 13−15 mmHg from baseline (P = 0.0001) but diastolic blood pressure did not. The mean plasma levels of total and LDL-cholesterol decreased 10.8% and 8.9% in women (P = 0.001), 21.5% and 22.2% in men (P = 0.001), respectively, while HDL-cholesterol and triglycerides remained stable. The proportion of those achieving targets in the treatment of dyslipidaemia increased significantly (P < 0.001). Conclusions: In this 22-year prospective follow-up study of in middle-aged Europeans with high participation rates, the progression of dysglycaemia to overt diabetes with aging was rapid, even without a significant change in BMI.
Published: 2021

5. Factors predicting 31-year survival among a population cohort in Northern Finland

Author: Perkkiö, Y. (Yrjö), Auvinen, J. (Juha), Timonen, M. (Markku), Jokelainen, J. (Jari), Valkeapää, N. (Nihkolas), Koiranen, M. (Markku), Saltevo, J. (Juha), Keinänen-Kiukaanniemi, S. (Sirkka), Perkkiö, Y. (Yrjö), Auvinen, J. (Juha), Timonen, M. (Markku), Jokelainen, J. (Jari), Valkeapää, N. (Nihkolas), Koiranen, M. (Markku), Saltevo, J. (Juha), and Keinänen-Kiukaanniemi, S. (Sirkka)
Abstract: We evaluated the survival of a subarctic population and the significance of traditional risk factors for mortality, causes of death and their seasonal variation from the period of 1984–2014. By the end of 2014 (follow-up), 644 (34.4% from 1,869) participants had died (42.1% of cardiovascular causes, 22.4% of neoplastic diseases). The average age at death±SD was 74.6±11.4 years for women (n=284) and 70.2±12.0 years for men (n=360). After adjusting for baseline age, the major risk factors predicting death were male sex (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.54–2.10), current smoking (HR 1.85; 95% CI 1.58–2.17), obesity (HR 1.75; 95% CI 1.45–2.12), high blood pressure (HR 1.46; 95% CI 1.24–1.72), cardiovascular disease (HR 1.62; 95% CI 1.36–1.93) and depression (HR 1.61; 95% CI 1.21–2.14) at baseline. The most common causes of death and the main risk factors predicting death in this population were the same as reported globally. Lifestyle factors had an important impact in predicting survival. The most common causes of death were the same for men and women. There was no significant difference in overall mortality rate between winter and summer, but cerebrovascular and pulmonary causes of death were more common during winter.
Published: 2021

6. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
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7. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author: Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), Chasman, D.I. (Daniel), Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), and Chasman, D.I. (Daniel)
Abstract: Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
Published: 2020
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8. Body size from birth to adulthood and bone mineral content and density at 31 years of age: results from the northern Finland 1966 birth cohort study

Author: Laitinen, J., Kiukaanniemi, K., Heikkinen, J., Koiranen, M., Nieminen, P., Sovio, U., Keinänen-Kiukaanniemi, S., and Järvelin, M. R.
Published: 2005
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9. A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort: Clinical and research diagnoses of schizophrenia

Author: Isohanni, M., Mäkikyrö, T., Moring, J., Räsanen, P., Hakko, H., Partanen, U., Koiranen, M., and Jones, P.
Published: 1997
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10. Juvenile offenders, with special reference to sex differences

Author: Rantakallio, P., Myhrman, A., and Koiranen, M.
Published: 1995
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11. BODY SIZE FROM BIRTH TO ADULTHOOD AND BONE MINERAL DENSITY AT 31 YEARS OF AGE

Author: Laitinen, J, Kiukaanniemi, K, Koiranen, M, Heikkinen, J, Kiukaanniemi-Keinänen, S, and Järvelin, M R
Published: 2003

12. The association between blood copper concentration and biomarkers related to cardiovascular disease risk:analysis of 206 individuals in the Northern Finland Birth Cohort 1966

Author: Palaniswamy, S. (Saranya), Piltonen, T. (Terhi), Koiranen, M. (Markku), Mazej, D. (Darja), Järvelin, M.-R. (Marjo-Riitta), Abass, K. (Khaled), Rautio, A. (Arja), and Sebert, S. (Sylvain)
Subjects: Young adult, Metabolomics, Inflammatory biomarkers, Metabolic profile, Cardiovascular disease risk, Copper
Abstract: Background: Copper is an abundant trace element in humans where alterations in the circulating concentration could inform on chronic disease aetiology. To date, data are lacking to study how copper may associate with cardiovascular disease (CVD) risk factors in young and healthy population. Molecular evidence suggests an important role of copper in liver metabolism, an essential organ in maintaining cardiovascular health and inflammation, therefore supporting copper as an associated biomarker of the risk. Objective: We performed a cross-sectional analysis to examine the possible associations between blood copper levels and risk factors for CVD and pre-inflammatory process. Design: The data has been collected from a sub-sample set of the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years. Participants: The study included 206 individuals, 116 men and 90 women. To reduce environmental individual variations affecting both copper and the metabolic profile in the study sample, the participants were selected as: i) being born in Finnish Lapland and ii) living in their birth place for the last five years preceding blood sampling. Main outcome measures: Fasting blood copper concentration was measured by inductively coupled plasma mass spectrometer. The CVD risk factors included 6 metabolic clusters (30 cardiovascular and pro-inflammatory factors) assessed by nuclear magnetic resonance. Multivariate linear regression analysis was performed to test the linear association between blood copper and 6 metabolic clusters for CVD risk. Associations were assessed under correction for multiple testing. Results: Copper (Cu) levels were comparable in men and women, with no difference between sexes (p-value
Published: 2018

13. Juvenile mortality, mental disturbances and criminality: a prospective study of the Northern Finland 1966 birth cohort

Author: Räsänen, P., Tiihonen, J., Isohanni, M., Moring, J., and Koiranen, M.
Published: 1998

14. Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort

Author: Isohanni, M, Jones, P.B, Moilanen, K, Rantakallio, P, Veijola, J, Oja, H, Koiranen, M, Jokelainen, J, Croudace, T, and Järvelin, M-R
Published: 2001
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15. Arsenic, cadmium, lead and mercury levels in blood of Finnish adults and their relation to diet, lifestyle habits and sociodemographic variables

Author: Abass, K. (Khaled), Koiranen, M. (Markku), Mazej, D. (Darja), Tratnik, J. S. (Janja Snoj), Horvat, M. (Milena), Hakkola, J. (Jukka), Järvelin, M.-R. (Marjo-Riitta), Rautio, A. (Arja), Abass, K. (Khaled), Koiranen, M. (Markku), Mazej, D. (Darja), Tratnik, J. S. (Janja Snoj), Horvat, M. (Milena), Hakkola, J. (Jukka), Järvelin, M.-R. (Marjo-Riitta), and Rautio, A. (Arja)
Abstract: The Northern Finland Birth Cohort program (NFBC) is the epidemiological and longitudinal prospective general population research program, which was established to promote health and wellbeing of the population in northern Finland. The aim of present study, as a part of the NFBC program, was to analyze the blood levels of arsenic (B-As), cadmium (B-Cd), lead (B-Pb), total mercury (B-Hg) and selenium (B-Se); to compare these levels with threshold limits; to study sociodemographic factors; and to correlate these levels with calcium and haemoglobin. The study was comprised of 249 NFBC subjects, of which 123 were female and 126 were male (ages 31.1 ± 0.3 and 31.1 ± 0.4, respectively). All participants were asked to complete a questionnaire regarding diet and living habits. The geometric means (± SD) of B-As were 0.49 ± 2.80 μg/l and 0.44 ± 2.72 μg/l; B-Cd were 0.18 ± 4.02 μg/l and 0.12 ± 3.21 μg/l; B-Pb were 17.0 ± 1.8 μg/l and 9.06 ± 2.20 μg/l; B-Hg were 2.18 ± 2.02 μg/l and 1.85 ± 1.78 μg/l; and B-Se were 106.0 ± 1.3 and 94.3 ± 1.3 μg/l in males and females, respectively. Among the subjects in the present analysis, 23 % of males and 17.1 % of females had B-As levels above the ATSDR normal human levels of B-As in unexposed individuals (1.0 μg/l). The B-Pb geometric mean (12.44 μg/l) was approximately one eighth the CDC toxicological cut-off point of 100 μg/l. Twenty-one individuals (8.4 %) exceeded a B-Hg level of 5.8 μg/l. Fifty-eight females (47 %) had a B-Hg higher than 2.0 μg/l, the German Federal Environmental Agency cut-off point for women (18–69 years) who consume fish at least three times/month; therefore, their babies could be at risk of adverse effects during development.
Published: 2017

16. Associations between school liking, loneliness and social relations among adolescents:Northern Finland Birth Cohort 1986 study

Author: Rönkä, A. R. (Anna Reetta), Sunnari, V. (Vappu), Rautio, A. (Arja), Koiranen, M. (Markku), Taanila, A. (Anja), Rönkä, A. R. (Anna Reetta), Sunnari, V. (Vappu), Rautio, A. (Arja), Koiranen, M. (Markku), and Taanila, A. (Anja)
Abstract: School is an important social environment, but it can also be a devastating place for those who experience loneliness, are bullied or have problematic social relations. These negative experiences might be associated with school dislike, which in turn can negatively affect pupil’s motivation, academic success and overall well-being. This study examined the associations between school liking with self-reports of experiences of loneliness and social relations in the Northern Finland Birth Cohort 1986. The answers of 16-year-olds to two adolescents’ questionnaires were investigated (n = 5817) using binomial logistic regression. For girls, variables associated with school dislike were being somewhat or very lonely, for girls and boys hanging around with friends/kids who get in trouble and for boys being afraid of going to school and not getting along with other adolescents. Schools should pay attention to creating safe and supporting social and learning environment so that everyone can thrive at school.
Published: 2017

17. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine (vol 48, pg 856, 2016)

Author: Gormley, P., Anttila, V., Winsvold, B.S., Palta, P., Esko, T., Pers, T.H., Farh, K.H., Cuenca-Leon, E., Muona, M., Furlotte, N.A., Kurth, T., Ingason, A., McMahon, G., Ligthart, L., Terwindt, G.M., Kallela, M., Freilinger, T.M., Ran, C., Gordon, S.G., Stam, A.H., Steinberg, S., Borck, G., Koiranen, M., Quaye, L., Adams, H.H.H., Lehtimaki, T., Sarin, A.P., Wedenoja, J., Hinds, D.A., Buring, J.E., Schurks, M., Ridker, P.M., Hrafnsdottir, M.G., Stefansson, H., Ring, S.M., Hottenga, J.J., Penninx, B.W.J.H., Farkkila, M., Artto, V., Kaunisto, M., Vepsalainen, S., Malik, R., Heath, A.C., Madden, P.A.F., Martin, N.G., Montgomery, G.W., Kurki, M.I., Kals, M., Magi, R., Parn, K., Hamalainen, E., Huang, H.L., Byrnes, A.E., Franke, L., Huang, J., Stergiakouli, E., Lee, P.H., Sandor, C., Webber, C., Cader, Z., Muller-Myhsok, B., Schreiber, S., Meitinger, T., Eriksson, J.G., Salomaa, V., Heikkila, K., Loehrer, E., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Cherkas, L., Pedersen, L.M., Stubhaug, A., Nielsen, C.S., Mannikko, M., Mihailov, E., Milani, L., Gobel, H., Esserlind, A.L., Christensen, A.F., Hansen, T.F., Werge, T., Kaprio, J., Aromaa, A.J., Raitakari, O., Ikram, M.A., Spector, T., Jarvelin, M.R., Metspalu, A., Kubisch, C., Strachan, D.P., Ferrari, M.D., Belin, A.C., Dichgans, M., Wessman, M., Maagdenberg, A.M.J.M. van den, Zwart, J.A., Boomsma, D.I., Smith, G.D., Stefansson, K., Eriksson, N., Daly, M.J., Neale, B.M., Olesen, J., Chasman, D.I., Nyholt, D.R., Palotie, A., and Int Headache Genetics Consortium
Published: 2016

18. Correction: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: Gormley, P, Anttila, V, Winsvold, BS, Palta, P, Esko, T, Pers, TH, Farh, KH, Cuenca-Leon, E, Muona, M, Furlotte, NA, Kurth, T, Ingason, A, McMahon, G, Ligthart, L, Terwindt, GM, Kallela, M, Freilinger, TM, Ran, C, Gordon, SG, Stam, AH, Steinberg, S, Borck, G, Koiranen, M, Quaye, L, Adams, HHH, Lehtimäki, T, Sarin, AP, Wedenoja, J, Hinds, DA, Buring, JE, Schürks, M, Ridker, PM, Gudlaug Hrafnsdottir, M, Stefansson, H, Ring, SM, Hottenga, JJ, Penninx, BWJH, Färkkilä, M, Artto, V, Kaunisto, M, Vepsäläinen, S, Malik, R, Heath, AC, Madden, PAF, Martin, NG, Montgomery, GW, Kurki, MI, Kals, M, Mägi, R, Pärn, K, Hämäläinen, E, Huang, H, Byrnes, AE, Franke, L, Huang, J, Stergiakouli, E, Lee, PH, Sandor, C, Webber, C, Cader, Z, Muller-Myhsok, B, Schreiber, S, Meitinger, T, Eriksson, JG, Salomaa, V, Heikkilä, K, Loehrer, E, Uitterlinden, AG, Hofman, A, Van Duijn, CM, Cherkas, L, Pedersen, LM, Stubhaug, A, Nielsen, CS, Männikkö, M, Mihailov, E, Milani, L, Göbel, H, Esserlind, AL, Francke Christensen, A, Folkmann Hansen, T, Werge, T, Kaprio, J, Aromaa, AJ, Raitakari, O, Arfan Ikram, M, Spector, T, Järvelin, MR, Metspalu, A, Kubisch, C, Strachan, DP, Ferrari, MD, Belin, AC, Dichgans, M, Wessman, M, Van den Maagdenberg, AMJM, Zwart, JA, Boomsma, DI, and Davey Smith, G
Subjects: ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology
Abstract: In the version of this article initially published online, the affiliations for Bertram Muller-Myhsok and Patricia Pozo-Rosich were incorrect or incomplete. These errors have been corrected for the print, PDF and HTML versions of this article.
Published: 2016

19. Hyperemesis gravidarum and cardiometabolic risk factors in adolescents: a follow-up of the Northern Finland Birth Cohort 1986

Author: Koot, MH, primary, Grooten, IJ, additional, Sebert, S, additional, Koiranen, M, additional, Järvelin, MR, additional, Kajantie, E, additional, Painter, RC, additional, and Roseboom, TJ, additional
Published: 2017
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20. Genome-wide meta-analysis identifies new susceptibility loci for migraine

Author: Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, Kallela M, Malik R, de Vries B, Terwindt G, Medland SE, Todt U, McArdle WL, Quaye L, Koiranen M, Ligthart L, Hottenga JJ, Vink JM, Penninx BW, Boomsma DI, Strachan DP, Kubisch C, Ferrari MD, van den Maagdenberg AM, Dichgans M, Wessman M, Smith GD, Stefansson K, Daly MJ, Nyholt DR, Chasman DI, Palotie A, North American Brain Expression Consortium, UK Brain Expression Consortium, International Headache Genetics Consortium, Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, Kallela M, Malik R, de Vries B, Terwindt G, Medland SE, Todt U, McArdle WL, Quaye L, Koiranen M, Ligthart L, Hottenga JJ, Vink JM, Penninx BW, Boomsma DI, Strachan DP, Kubisch C, Ferrari MD, van den Maagdenberg AM, Dichgans M, Wessman M, Smith GD, Stefansson K, Daly MJ, Nyholt DR, Chasman DI, and Palotie A
Published: 2013

21. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), and Palotie, A. (Aarno)
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10-8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016
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22. Long-term unemployment is associated with short telomeres in 31-year-old men : an observational study in the Northern Finland Birth Cohort 1966

Author: Ala-Mursula, L, Buxton, JL, Ek, E, Koiranen, M, Taanila, A, Blakemore, AIF, Jarvelin, M-R, and Medical Research Council (MRC)
Subjects: BIOMARKER, Male, General Science & Technology, LIFE STRESS, DISEASE, Cohort Studies, AGE, LENGTH, EPIDEMIOLOGY, EMPLOYMENT, Humans, Finland, WORK, Science & Technology, MULTIDISCIPLINARY SCIENCES, WOMEN, Middle Aged, Telomere, CANCER, Multidisciplinary Sciences, Socioeconomic Factors, Unemployment, Science & Technology - Other Topics, HEALTH, FOLLOW-UP, biological
Abstract: OBJECTIVE:\ud Life stress resulting from early-life experiences and domestic stress is linked with shorter leukocyte telomere length (LTL), but evidence on employment-related stress is scarce. We explored whether unemployment in early adulthood is associated with shorter LTL, a potential biomarker of premature aging.\ud \ud METHODS:\ud We used data from 5620 men and women belonging to the Northern Finland Birth Cohort 1966. Individually registered unemployment days in 1995-97 were compared with data on biological, behavioral and socioeconomic health predictors and existing medical conditions obtained by surveys and clinical examinations at follow-up in 1997-98. Mean LTL at follow-up was measured by multiplex quantitative real-time PCR. We calculated odds ratios and their 95% confidence intervals (CI) of belonging to the sex-stratified shortest decile of standardized relative mean LTL according to the categories of: 0
Published: 2013

23. The association of genotype-based inbreeding coefficient with a range of physical and psychological human traits

Author: Verweij, K.J.H., Abdellaoui, A., Veijola, J., Sebert, S., Koiranen, M., Keller, M.C., Jarvelin, M.R., Zietsch, B.P., Verweij, K.J.H., Abdellaoui, A., Veijola, J., Sebert, S., Koiranen, M., Keller, M.C., Jarvelin, M.R., and Zietsch, B.P.
Abstract: Contains fulltext : 156145.PDF (publisher's version ) (Open Access), Across animal species, offspring of closely related mates exhibit lower fitness, a phenomenon called inbreeding depression. Inbreeding depression in humans is less well understood because mating between close relatives is generally rare and stigmatised, confounding investigation of its effect on fitness-relevant traits. Recently, the availability of high-density genotype data has enabled quantification of variation in distant inbreeding in 'outbred' human populations, but the low variance of inbreeding detected from genetic data in most outbred populations means large samples are required to test effects, and only a few traits have yet been studied. However, it is likely that isolated populations, or those with a small effective population size, have higher variation in inbreeding and therefore require smaller sample sizes to detect inbreeding effects. With a small effective population size and low immigration, Northern Finland is such a population. We make use of a sample of similar to 5,500 'unrelated individuals in the Northern Finnish Birth Cohort 1966 with known genotypes and measured phenotypes across a range of fitness-relevant physical and psychological traits, including birth length and adult height, body mass index (BMI), waist-to-hip ratio, blood pressure, heart rate, grip strength, educational attainment, income, marital status, handedness, health, and schizotypal features. We find significant associations in the predicted direction between individuals' inbreeding coefficient (measured by proportion of the genome in runs of homozygosity) and eight of the 18 traits investigated, significantly more than the one or two expected by chance. These results are consistent with inbreeding depression effects on a range of human traits, but further research is needed to replicate and test alternative explanations for these effects.
Published: 2014

24. Le imprese familiari: sistemi di generazione di valore attraverso le generazioni

Author: Colombo, Gianluca, Koiranen, M., and Chirico, F.
Published: 2008

25. Understanding Family Businesses as Value Creation Systems through System Dynamics

Author: Colombo, Gianluca, Koiranen, M., and Chirico, F.
Published: 2006

26. Genome-wide meta-analysis identifies new susceptibility loci for migraine

Author: Anttila, V., Winsvold, B.S., Gormley, P., Kurth, T., Bettella, F., McMahon, G., Kallela, M., Malik, R., de Vries, B., Terwindt, G., Medland, S.E., Todt, U., McArdle, W.L., Quaye, L., Koiranen, M., Ikram, M.A., Lehtimäki, T., Stam, A.H., Ligthart, L., Wedenoja, J., Dunham, I., Neale, B. M., Palta, P., Hamalainen, E., Schürks, M., Rose, L.M., Buring, J.E., Ridker, P.M., Steinberg, S., Stefansson, H., Jakobsson, F., Lawlor, D.A., Evans, D.M., Ring, S.M., Färkkilä, M., Artto, V., Kaunisto, M.A., Freilinger, T., Schoenen, J., Frants, R.R., Pelzer, N., Weller, C.M., Zielman, R., Heath, A.C., Madden, P.A.F., Montgomery, G.W., Martin, N.G., Borck, G., Göbel, H., Heinze, A., Heinze-Kuhn, K., Williams, F.M., Hartikainen, A.-L., Pouta, A., van den Ende, J.., Uitterlinden, A.G., Hofman, A., Amin, N., Hottenga, J.J., Vink, J.M., Heikkilä, K., Alexander, M., Muller-Myhsok, B., Schreiber, S, Meitinger, T., Wichmann, H. E., Aromaa, A., Eriksson, J.G., Traynor, B.J., Trabzuni, D., Rossin, E., Lage, K., Jacobs, S.B., Gibbs, J.R., Birney, E., Kaprio, J., Penninx, B.W.J.H., Boomsma, D.I., van Duijn, C.M., Raitakari, O., Jarvelin, M.-R., Zwart, J.A., Cherkas, L., Strachan, D.P., Kubisch, C., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Dichgans, M., Wessman, M., Smith, G.D., Stefansson, K., Daly, M.J., Nyholt, DR, Chasman, D.I., Palotie, A., Anttila, V., Winsvold, B.S., Gormley, P., Kurth, T., Bettella, F., McMahon, G., Kallela, M., Malik, R., de Vries, B., Terwindt, G., Medland, S.E., Todt, U., McArdle, W.L., Quaye, L., Koiranen, M., Ikram, M.A., Lehtimäki, T., Stam, A.H., Ligthart, L., Wedenoja, J., Dunham, I., Neale, B. M., Palta, P., Hamalainen, E., Schürks, M., Rose, L.M., Buring, J.E., Ridker, P.M., Steinberg, S., Stefansson, H., Jakobsson, F., Lawlor, D.A., Evans, D.M., Ring, S.M., Färkkilä, M., Artto, V., Kaunisto, M.A., Freilinger, T., Schoenen, J., Frants, R.R., Pelzer, N., Weller, C.M., Zielman, R., Heath, A.C., Madden, P.A.F., Montgomery, G.W., Martin, N.G., Borck, G., Göbel, H., Heinze, A., Heinze-Kuhn, K., Williams, F.M., Hartikainen, A.-L., Pouta, A., van den Ende, J.., Uitterlinden, A.G., Hofman, A., Amin, N., Hottenga, J.J., Vink, J.M., Heikkilä, K., Alexander, M., Muller-Myhsok, B., Schreiber, S, Meitinger, T., Wichmann, H. E., Aromaa, A., Eriksson, J.G., Traynor, B.J., Trabzuni, D., Rossin, E., Lage, K., Jacobs, S.B., Gibbs, J.R., Birney, E., Kaprio, J., Penninx, B.W.J.H., Boomsma, D.I., van Duijn, C.M., Raitakari, O., Jarvelin, M.-R., Zwart, J.A., Cherkas, L., Strachan, D.P., Kubisch, C., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Dichgans, M., Wessman, M., Smith, G.D., Stefansson, K., Daly, M.J., Nyholt, DR, Chasman, D.I., and Palotie, A.
Abstract: Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 × 10
Published: 2013
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27. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, H.L., Estrada Gil, K. (Karol), Lettre, G. (Guillaume), Berndt, S.I. (Sonja), Rivadeneira Ramirez, F. (Fernando), Willer, C.J. (Cristen), Jackson, A.U. (Anne), Vedantam, S. (Sailaja), Raychaudhuri, S. (Soumya), Ferreira, T. (Teresa), Wood, A.R. (Andrew), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Speliotes, E.K. (Elizabeth), Wheeler, E. (Eleanor), Soranzo, N. (Nicole), Park, J.H., Yang, J. (Joanna), Gudbjartsson, D.F. (Daniel), Heard-Costa, N.L. (Nancy), Randall, J.C. (Joshua), Qi, L. (Lu), Smith, A.V. (Albert Vernon), Mägi, R. (Reedik), Pastinen, T. (Tomi), Liang, L. (Liming), Heid, I.M. (Iris), Luan, J., Thorleifsson, G. (Gudmar), Winkler, T.W. (Thomas), Goddard, M.E. (Michael), Lo, K.S., Palmer, C. (Cameron), Workalemahu, T. (Tsegaselassie), Aulchenko, Y.S. (Yurii), Johansson, A. (Åsa), Zillikens, M.C. (Carola), Feitosa, M.F. (Mary Furlan), Esko, T. (Tõnu), Johnson, T. (Toby), Ketkar, S. (Shamika), Kraft, P. (Peter), Mangino, M. (Massimo), Prokopenko, I. (Inga), Absher, D. (Devin), Albrecht, E. (Eva), Ernst, F.D.J. (Florian), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Hottenga, J.J. (Jouke Jan), Jacobs, K.B. (Kevin), Knowles, J.W. (Joshua), Kutalik, Z. (Zoltán), Monda, K.L. (Keri), Polasek, O. (Ozren), Preuss, M. (Michael), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Steinthorsdottir, V. (Valgerdur), Tyrer, J.P. (Jonathan), Voight, B.F. (Benjamin), Wiklund, F. (Fredrik), Xu, J. (Jianfeng), Zhao, J.H. (Jing Hua), Nyholt, D.R. (Dale), Pellikka, N. (Niina), Perola, M. (Markus), Perry, J.R.B. (John), Surakka, I. (Ida), Tammesoo, M.L., Altmaier, E.L. (Elizabeth), Amin, N. (Najaf), Aspelund, T. (Thor), Bhangale, T. (Tushar), Boucher, G. (Gabrielle), Chasman, D.I. (Daniel), Chen, C. (Constance), Coin, L. (Lachlan), Cooper, M.N. (Matthew), Dixon, A.L. (Anna), Gibson, Q. (Quince), Grundberg, E. (Elin), Hao, K. (Ke), Junttila, M.J. (Juhani), Kaplan, R.C. (Robert), Kettunen, J. (Johannes), König, I.R. (Inke), Kwan, T. (Tony), Lawrence, R.W. (Robert), Levinson, D.F. (Douglas), Lorentzon, M. (Mattias), McKnight, B. (Barbara), Morris, A.D. (Andrew), Müller, M. (Martina), Ngwa, J.S., Purcell, S. (Shaun), Rafelt, S. (Suzanne), Salem, R.M. (Rany), Salvi, E. (Erika), Sanna, S. (Serena), Shi, J. (Jianxin), Sovio, U. (Ulla), Thompson, J.R. (John), Turchin, M.C. (Michael), Vandenput, L. (Liesbeth), Verlaan, D.J. (Dominique), Vitart, V. (Veronique), White, C.C. (Charles), Ziegler, A. (Andreas), Almgren, P. (Peter), Balmforth, A.J. (Anthony), Campbell, H. (Harry), Citterio, L. (Lorena), Grandi, A. (Alessandro) de, Dominiczak, A. (Anna), Duan, J. (Jubao), Elliott, P. (Paul), Elosua, R. (Roberto), Eriksson, J.G. (Johan), Freimer, N.B. (Nelson), Geus, E.J.C. (Eco) de, Glorioso, N. (Nicola), Haiqing, S. (Shen), Hartikainen, A.L., Havulinna, A.S. (Aki), Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Illig, T. (Thomas), Jula, A. (Antti), Kajantie, E. (Eero), Kilpeläinen, T.O. (Tuomas), Koiranen, M. (Markku), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Laitinen, J. (Jaana), Liu, J. (Jianjun), Lokki, M.L., Marusic, A. (Ana), Maschio, A., Meitinger, T. (Thomas), Mulas, A. (Antonella), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Petersmann, A. (Astrid), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Rotter, J.I. (Jerome), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Schmidt, C.O. (Carsten Oliver), Sinisalo, J. (Juha), Smit, J.H. (Jan), Stringham, H.M. (Heather), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Zagato, L. (Laura), Zgaga, L. (Lina), Zitting, P. (Paavo), Alavere, H. (Helene), Farrall, M. (Martin), McArdle, W.L. (Wendy), Nelis, M. (Mari), Peters, M.J. (Marjolein), Ripatti, S. (Samuli), Meurs, J.B.J. (Joyce) van, Aben, K.K.H. (Katja), Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Collins, F.S. (Francis), Cusi, D. (Daniele), Heijer, M. (Martin) den, Eiriksdottir, G. (Gudny), Gejman, P.V. (Pablo), Hall, A.S. (Alistair), Hamsten, A. (Anders), Huikuri, H.V. (Heikki), Iribarren, C. (Carlos), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), Melander, O. (Olle), Mosley, T.H. (Thomas), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), O'Donnell, C.J. (Christopher), Ohlsson, C. (Claes), Oostra, B.A. (Ben), Raitakari, O. (Olli), Ridker, P.M. (Paul), Rioux, J.D. (John), Rissanen, A. (Aila), Rivolta, C. (Carlo), Schunkert, H. (Heribert), Shuldiner, A.R. (Alan), Siscovick, D.S. (David), Stumvoll, M. (Michael), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Ommen, G.J. (Gert) van, Viikari, J. (Jorma), Heath, A.C. (Andrew), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Province, M.A. (Mike), Kayser, M.H. (Manfred), Arnold, A.M. (Alice), Atwood, L.D. (Larry), Boerwinkle, E.A. (Eric), Chanock, S.J. (Stephen), Deloukas, P. (Panagiotis), Gieger, C. (Christian), Grönberg, H. (Henrik), Hattersley, A.T. (Andrew), Hengstenberg, C. (Christian), Hoffman, W. (Wolfgang), Lathrop, G.M. (Mark), Salomaa, V. (Veikko), Schreiber, S. (Stefan), Uda, M. (Manuela), Waterworth, D. (Dawn), Wright, A.F. (Alan), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Hofman, A. (Albert), Mohlke, K.L. (Karen), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Cupples, L.A. (Adrienne), Fox, C.S. (Caroline), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Harris, T.B. (Tamara), Hayes, R.B. (Richard), Järvelin, M.R., Mooser, V. (Vincent), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Rudan, I. (Igor), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Völzke, H. (Henry), Watkins, H. (Hugh), Wilson, J.F. (James), Groop, L. (Leif), Haritunians, T. (Talin), Hu, F.B. (Frank), Metspalu, A. (Andres), North, K.E. (Kari), Schlessinger, D., Wareham, N.J. (Nick), Hunter, D.J. (David), O´Connell, J.R., Strachan, D.P. (David), Wichmann, H.E. (Heinz Erich), Borecki, I.B. (Ingrid), Duijn, C.M. (Cornelia) van, Schadt, E.E. (Eric), Thorsteinsdottir, U. (Unnur), Peltonen, L. (Leena Johanna), Uitterlinden, A.G. (André), Visscher, P.M. (Peter), Chatterjee, N. (Nilanjan), Erdmann, J. (Jeanette), Loos, R.J.F. (Ruth), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Lindgren, C.M. (Cecilia), Abecasis, G.R. (Gonçalo), Stefansson, K. (Kari), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Ardlie, K.G. (Kristin), Weedon, M.N. (Michael), Allen, H.L., Estrada Gil, K. (Karol), Lettre, G. (Guillaume), Berndt, S.I. (Sonja), Rivadeneira Ramirez, F. (Fernando), Willer, C.J. (Cristen), Jackson, A.U. (Anne), Vedantam, S. (Sailaja), Raychaudhuri, S. (Soumya), Ferreira, T. (Teresa), Wood, A.R. (Andrew), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Speliotes, E.K. (Elizabeth), Wheeler, E. (Eleanor), Soranzo, N. (Nicole), Park, J.H., Yang, J. (Joanna), Gudbjartsson, D.F. (Daniel), Heard-Costa, N.L. (Nancy), Randall, J.C. (Joshua), Qi, L. (Lu), Smith, A.V. (Albert Vernon), Mägi, R. (Reedik), Pastinen, T. (Tomi), Liang, L. (Liming), Heid, I.M. (Iris), Luan, J., Thorleifsson, G. (Gudmar), Winkler, T.W. (Thomas), Goddard, M.E. (Michael), Lo, K.S., Palmer, C. (Cameron), Workalemahu, T. (Tsegaselassie), Aulchenko, Y.S. (Yurii), Johansson, A. (Åsa), Zillikens, M.C. (Carola), Feitosa, M.F. (Mary Furlan), Esko, T. (Tõnu), Johnson, T. (Toby), Ketkar, S. (Shamika), Kraft, P. (Peter), Mangino, M. (Massimo), Prokopenko, I. (Inga), Absher, D. (Devin), Albrecht, E. (Eva), Ernst, F.D.J. (Florian), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Hottenga, J.J. (Jouke Jan), Jacobs, K.B. (Kevin), Knowles, J.W. (Joshua), Kutalik, Z. (Zoltán), Monda, K.L. (Keri), Polasek, O. (Ozren), Preuss, M. (Michael), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Steinthorsdottir, V. (Valgerdur), Tyrer, J.P. (Jonathan), Voight, B.F. (Benjamin), Wiklund, F. (Fredrik), Xu, J. (Jianfeng), Zhao, J.H. (Jing Hua), Nyholt, D.R. (Dale), Pellikka, N. (Niina), Perola, M. (Markus), Perry, J.R.B. (John), Surakka, I. (Ida), Tammesoo, M.L., Altmaier, E.L. (Elizabeth), Amin, N. (Najaf), Aspelund, T. (Thor), Bhangale, T. (Tushar), Boucher, G. (Gabrielle), Chasman, D.I. (Daniel), Chen, C. (Constance), Coin, L. (Lachlan), Cooper, M.N. (Matthew), Dixon, A.L. (Anna), Gibson, Q. (Quince), Grundberg, E. (Elin), Hao, K. (Ke), Junttila, M.J. (Juhani), Kaplan, R.C. (Robert), Kettunen, J. (Johannes), König, I.R. (Inke), Kwan, T. (Tony), Lawrence, R.W. (Robert), Levinson, D.F. (Douglas), Lorentzon, M. (Mattias), McKnight, B. (Barbara), Morris, A.D. (Andrew), Müller, M. (Martina), Ngwa, J.S., Purcell, S. (Shaun), Rafelt, S. (Suzanne), Salem, R.M. (Rany), Salvi, E. (Erika), Sanna, S. (Serena), Shi, J. (Jianxin), Sovio, U. (Ulla), Thompson, J.R. (John), Turchin, M.C. (Michael), Vandenput, L. (Liesbeth), Verlaan, D.J. (Dominique), Vitart, V. (Veronique), White, C.C. (Charles), Ziegler, A. (Andreas), Almgren, P. (Peter), Balmforth, A.J. (Anthony), Campbell, H. (Harry), Citterio, L. (Lorena), Grandi, A. (Alessandro) de, Dominiczak, A. (Anna), Duan, J. (Jubao), Elliott, P. (Paul), Elosua, R. (Roberto), Eriksson, J.G. (Johan), Freimer, N.B. (Nelson), Geus, E.J.C. (Eco) de, Glorioso, N. (Nicola), Haiqing, S. (Shen), Hartikainen, A.L., Havulinna, A.S. (Aki), Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Illig, T. (Thomas), Jula, A. (Antti), Kajantie, E. (Eero), Kilpeläinen, T.O. (Tuomas), Koiranen, M. (Markku), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Laitinen, J. (Jaana), Liu, J. (Jianjun), Lokki, M.L., Marusic, A. (Ana), Maschio, A., Meitinger, T. (Thomas), Mulas, A. (Antonella), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Petersmann, A. (Astrid), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Rotter, J.I. (Jerome), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Schmidt, C.O. (Carsten Oliver), Sinisalo, J. (Juha), Smit, J.H. (Jan), Stringham, H.M. (Heather), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Zagato, L. (Laura), Zgaga, L. (Lina), Zitting, P. (Paavo), Alavere, H. (Helene), Farrall, M. (Martin), McArdle, W.L. (Wendy), Nelis, M. (Mari), Peters, M.J. (Marjolein), Ripatti, S. (Samuli), Meurs, J.B.J. (Joyce) van, Aben, K.K.H. (Katja), Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Collins, F.S. (Francis), Cusi, D. (Daniele), Heijer, M. (Martin) den, Eiriksdottir, G. (Gudny), Gejman, P.V. (Pablo), Hall, A.S. (Alistair), Hamsten, A. (Anders), Huikuri, H.V. (Heikki), Iribarren, C. (Carlos), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lehtimäki, T. (Terho), Melander, O. (Olle), Mosley, T.H. (Thomas), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), O'Donnell, C.J. (Christopher), Ohlsson, C. (Claes), Oostra, B.A. (Ben), Raitakari, O. (Olli), Ridker, P.M. (Paul), Rioux, J.D. (John), Rissanen, A. (Aila), Rivolta, C. (Carlo), Schunkert, H. (Heribert), Shuldiner, A.R. (Alan), Siscovick, D.S. (David), Stumvoll, M. (Michael), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Ommen, G.J. (Gert) van, Viikari, J. (Jorma), Heath, A.C. (Andrew), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Province, M.A. (Mike), Kayser, M.H. (Manfred), Arnold, A.M. (Alice), Atwood, L.D. (Larry), Boerwinkle, E.A. (Eric), Chanock, S.J. (Stephen), Deloukas, P. (Panagiotis), Gieger, C. (Christian), Grönberg, H. (Henrik), Hattersley, A.T. (Andrew), Hengstenberg, C. (Christian), Hoffman, W. (Wolfgang), Lathrop, G.M. (Mark), Salomaa, V. (Veikko), Schreiber, S. (Stefan), Uda, M. (Manuela), Waterworth, D. (Dawn), Wright, A.F. (Alan), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Hofman, A. (Albert), Mohlke, K.L. (Karen), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Cupples, L.A. (Adrienne), Fox, C.S. (Caroline), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Harris, T.B. (Tamara), Hayes, R.B. (Richard), Järvelin, M.R., Mooser, V. (Vincent), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Rudan, I. (Igor), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Völzke, H. (Henry), Watkins, H. (Hugh), Wilson, J.F. (James), Groop, L. (Leif), Haritunians, T. (Talin), Hu, F.B. (Frank), Metspalu, A. (Andres), North, K.E. (Kari), Schlessinger, D., Wareham, N.J. (Nick), Hunter, D.J. (David), O´Connell, J.R., Strachan, D.P. (David), Wichmann, H.E. (Heinz Erich), Borecki, I.B. (Ingrid), Duijn, C.M. (Cornelia) van, Schadt, E.E. (Eric), Thorsteinsdottir, U. (Unnur), Peltonen, L. (Leena Johanna), Uitterlinden, A.G. (André), Visscher, P.M. (Peter), Chatterjee, N. (Nilanjan), Erdmann, J. (Jeanette), Loos, R.J.F. (Ruth), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Lindgren, C.M. (Cecilia), Abecasis, G.R. (Gonçalo), Stefansson, K. (Kari), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Ardlie, K.G. (Kristin), and Weedon, M.N. (Michael)
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P<0.001). Second, the likely causal gene is often located near the most str
Published: 2010
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28. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, Hirschhorn, JN, Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, and Hirschhorn, JN
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can ide
Published: 2010

29. Linguistic and motor abilities of low-birthweight children as assessed by parents and teachers at 8 years of age

Author: Yliherva, A, primary, Olsén, P, additional, Mäki-Torkko, E, additional, Koiranen, M, additional, and Järvelin, M-R, additional
Published: 2007
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30. A 28 year follow up of mortality among women who smoked during pregnancy

Author: Rantakallio, P., primary, Laara, E., additional, and Koiranen, M., additional
Published: 1995
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31. Association of perinatal events, epilepsy, and central nervous system trauma with juvenile delinquency.

Author: Rantakallio, P, primary, Koiranen, M, additional, and Mottonen, J, additional
Published: 1992
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32. Physical workload and risk of low back pain in adolescence.

Author: Mikkonen P, Viikari-Juntura E, Remes J, Pienimäki T, Solovieva S, Taimela S, Zitting P, Koiranen M, Leino-Arjas P, and Karppinen J
Abstract: Objectives To evaluate the role of physical workload in low back pain (LBP) among adolescents. Methods Working history and physical workload factors at 18 years were assessed for 1984 members of the Northern Finland Birth Cohort 1986. The associations between work characteristics and LBP were analysed by multinomial logistic regression. Those with and without LBP at 18 years of age were compared in two subsamples. The incidence of LBP was studied among the 986 subjects without LBP at 16 years of age. Persistence of LBP was studied among the 728 subjects with LBP at 16 years of age. Latent class analysis (LCA) was used to form natural clusters of workload factors and their associations with LBP were investigated using log-binomial regression. Results 753 (75%) subjects without LBP at 16 years of age had been working during the 2-year follow-up period. The average duration of work was 6.2 months. In adolescent girls, working regularly or irregularly and duration of work exposure were associated with incident LBP. Of specific physical workload factors, only awkward trunk postures were associated with incident LBP in both genders (RR 1.2 in girls and 1.7 in boys). The work exposure patterns in adolescent girls and boys were different. In the LCA, subjects in a cluster with high exposure to awkward trunk postures or an overall physically demanding job had a higher likelihood of incident LBP in both genders (RR 1.3-1.9). None of the specific workload factors or clusters was associated with persistent LBP. Conclusions Physical workload factors constitute a risk for LBP even in adolescents. [ABSTRACT FROM AUTHOR]
Published: 2012

33. Psychosocial factors as mediators between migration and subjective well-being among young Finnish adults.

Author: Ek E, Koiranen M, Raatikka V, Järvelin MR, and Taanila A
Abstract: This study examined the role of socioeconomic factors (such as education and employment) and psychosocial factors (such as social support, coping and attitude towards the future), in the relationship between migration, self-reported health and life satisfaction among young adults in a 31-year follow-up study of the Northern Finland Birth Cohort 1966 conducted in 1997-1998. The associations between these outcomes and socioeconomic and psychosocial factors were first examined, stratified by gender and migration, for sample members at 23 and at 31 years of age. Regression modelling was then used to study the association between migration and the outcomes after adjusting for specific socioeconomic and psychosocial factors. Results of binary logistic regression models showed that, although there was more dissatisfaction with life and more poor self-reported health in rural areas, the association was derived mostly from the mediation of unemployment, poorer education, lack of social support, passive coping strategies and greater pessimism among people living in rural areas. It is concluded that special attention should be paid to improving living conditions (educational and vocational opportunities) and enhancing the psychosocial resources of young adults in rural and remote areas. [ABSTRACT FROM AUTHOR]
Published: 2008

34. Linguistic and motor abilities of low-birthweight children as assessed by parents and teachers at 8 years of age.

Author: Yliherva, A, Olsén, P, Mäki-Torkko, E, Koiranen, M, Järvelin, M-R, Olsén, P, Mäki-Torkko, E, and Järvelin, M R
Subjects: LOW birth weight, MOTOR ability
Abstract: Unlabelled: Linguistic and motor abilities among low-birthweight 8-y-old children in the northern Finland Birth Cohort for 1985-1986 (n = 9322) were studied using parental and teacher evaluations. The parents of 8370 (90%) and teachers of 8525 (92%) children returned a mailed questionnaire concerning the children's speech, language, learning and motor abilities. Low-birthweight (LBW, < 2500 g) children (n = 279) appeared to have experienced more difficulties than normal-birthweight (NBW, > or = 2500 g) children (n = 8091). The parents evaluated the LBW boys to be the poorest in linguistic and motor skills compared with the other boys or any of the groups of girls. They are therefore presumably at risk of having problems at school, which was confirmed by the teachers' reports. There was also a clear relationship between speech/linguistic and motor disabilities.Conclusion: Multivariate logistic regression analyses showed that the lower birthweight and some sociodemographic factors, for example the mother's age being between 20 and 24 y, having more than four children in the family, a reconstructed family, as well as hearing impairment and male gender were the most important determinants of poor speech and language abilities at 8 y of age, with and without adjustment for neonatal risk factors (asphyxia, convulsions, respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus). Smallness for gestational age was also a risk factor for poor speech and language skills. Preterm birth was associated with poor skills only after adjustment for the neonatal risk factor. The parental and teacher evaluations were concordant concerning the LBW children's outcome. [ABSTRACT FROM AUTHOR]
Published: 2001
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35. Has the intrauterine weight-gain curve changed in shape?

Author: RANTAKALLIO, PAULA, OJA, HANNU, KOIRANEN, MARKKU, Rantakallio, P, Oja, H, and Koiranen, M
Published: 1991
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36. Maternal build and pregnancy outcome

Author: Rantakallio, P., Laeaerae, E., Koiranen, M., and Sarpola, A.
Published: 1995
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37. Erectile dysfunction as a predictive indicator of asymptomatic diabetes and prediabetes.

Author: Becker S, Suija K, Valpas A, Koiranen M, Auvinen J, Uusitalo H, Hussi E, Keinänen-Kiukaanniemi S, Tuomilehto J, and Saramies J
Abstract: Aims: Both erectile dysfunction (ED) and diabetes (DM) are common health problems that share risk factors. The aim of this study was to investigate whether ED can predict glucose metabolism dysfunctions in men at the primary care level., Methods: An 11-year population-based cohort study was conducted in men born between 1933 and 1956. The baseline survey was conducted in 2007-2008, with a follow-up examination 11 years later. The International Index of Erectile Function (IIEF-5) questionnaire was used to assess erectile function. Dysglycemia was evaluated using and a 2-hour oral glucose tolerance test (2hOGTT), in combination with health registry data., Results: At baseline, men with ED but without a history of known DM exhibited a significantly higher prevalence of undetected DM, odds ratio (OR) 4.7 (95 % CI 1.6, 14.4), and preDM, OR 1.9 (1.1, 3.2), compared with men without ED. Over an 11-year follow-up period, a significantly increased cumulative incidence of DM was observed in men who reported symptoms of ED at the start of the study., Conclusions: The symptoms of ED appear to be an early warning sign of existing DM and preDM and predict an increased risk of developing abnormal glucose metabolism in the future., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)
Published: 2024
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38. A Natural History of Erectile Dysfunction in Elderly Men: A Population-Based, Twelve-Year Prospective Study.

Author: Saramies J, Koiranen M, Auvinen J, Uusitalo H, Hussi E, Becker S, Keinänen-Kiukaanniemi S, Tuomilehto J, and Suija K
Abstract: There is a wide variation in the development and course of erectile dysfunction (ED) in men, which confirms the need for prospective studies. We conducted a cross-sectional analysis among the general male population at the baseline ( n = 359) and in a follow-up survey ( n = 218) 12 years later. The prospective 12-year study included 189 men. ED was assessed using the International Index of Erectile Function questionnaire. The mean age of the participants was 62.0 years at the baseline, while at the 12-year follow-up it was 71.6 years. The crude prevalence of ED was 61.6% at the baseline and 78.9% at the follow-up, and the prevalence tended to increase with age. All of the men aged 75 years or more had at least mild ED. The incidence of ED in every thousand person years was 53.5. A total of 54.5% of the men experienced ED progression, while 39.2% reported no changes in erectile function, and 6.3% experienced ED regression during the 12-year study. The likelihood of ED progression was higher in the older compared with younger age group (odds ratio, OR 5.2 (95% CI: 1.1-26.2)), and the likelihood of ED regression was lower among men with increased depression symptoms (OR 0.3 (95% CI: 0.1-0.6)) and among men with a decreased interest in their sexual life (OR 0.1 (95% CI: 0.0-0.6)). Lifestyle factors such as the consumption of alcohol and smoking were not significantly associated with ED.
Published: 2022
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39. Factors predicting 31-year survival among a population cohort in Northern Finland.

Author: Perkkiö Y, Auvinen J, Timonen M, Jokelainen J, Valkeapää N, Koiranen M, Saltevo J, and Keinänen-Kiukaanniemi S
Subjects: Cohort Studies, Female, Finland epidemiology, Humans, Male, Proportional Hazards Models, Risk Factors, Cardiovascular Diseases
Abstract: We evaluated the survival of a subarctic population and the significance of traditional risk factors for mortality, causes of death and their seasonal variation from the period of 1984-2014. By the end of 2014 (follow-up), 644 (34.4% from 1,869) participants had died (42.1% of cardiovascular causes, 22.4% of neoplastic diseases). The average age at death±SD was 74.6±11.4 years for women (n=284) and 70.2±12.0 years for men (n=360). After adjusting for baseline age, the major risk factors predicting death were male sex (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.54-2.10), current smoking (HR 1.85; 95% CI 1.58-2.17), obesity (HR 1.75; 95% CI 1.45-2.12), high blood pressure (HR 1.46; 95% CI 1.24-1.72), cardiovascular disease (HR 1.62; 95% CI 1.36-1.93) and depression (HR 1.61; 95% CI 1.21-2.14) at baseline.The most common causes of death and the main risk factors predicting death in this population were the same as reported globally. Lifestyle factors had an important impact in predicting survival. The most common causes of death were the same for men and women. There was no significant difference in overall mortality rate between winter and summer, but cerebrovascular and pulmonary causes of death were more common during winter.
Published: 2021
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40. 22-year trends in dysglycemia and body mass index: A population-based cohort study in Savitaipale, Finland.

Author: Saramies J, Koiranen M, Auvinen J, Uusitalo H, Hussi E, Cederberg H, Keinänen-Kiukaanniemi S, and Tuomilehto J
Subjects: Body Mass Index, Cohort Studies, Female, Finland epidemiology, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology
Abstract: Aims: We describe a 22-year prospective observational population-based study that determined the prevalence and incidence of type 2 diabetes (T2D) and intermediate hyperglycaemia (IH), obesity, hypertension, and disorders of lipid metabolism in a middle-age population in the Finnish municipality of Savitaipale., Methods: 1151 people participated in the baseline survey in 1996-1999, following two follow-up examinations, in 2007-2008 and 2018-2019. Follow-up studies comprised clinical measurements, 2-h oral glucose tolerance test and other biochemistry, questionnaires, and registry data., Results: The prevalence of T2D quadrupled to 27% and the proportion of normoglycemic people decreased from 73% to 44% while IH increased only slightly during the 22-year follow-up. A large proportion of people who died between the surveys were diabetic. The mean body mass index (BMI) did not, whereas mean waist circumference increased significantly, by 5-6 cm (P = 0.001) during the 22 years. Systolic blood pressure increased by 13-15 mmHg from baseline (P = 0.0001) but diastolic blood pressure did not. The mean plasma levels of total and LDL-cholesterol decreased 10.8% and 8.9% in women (P = 0.001), 21.5% and 22.2% in men (P = 0.001), respectively, while HDL-cholesterol and triglycerides remained stable. The proportion of those achieving targets in the treatment of dyslipidaemia increased significantly (P < 0.001)., Conclusions: In this 22-year prospective follow-up study of in middle-aged Europeans with high participation rates, the progression of dysglycaemia to overt diabetes with aging was rapid, even without a significant change in BMI., (Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)
Published: 2021
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41. The association between blood copper concentration and biomarkers related to cardiovascular disease risk - analysis of 206 individuals in the Northern Finland Birth Cohort 1966.

Author: Palaniswamy S, Piltonen T, Koiranen M, Mazej D, Järvelin MR, Abass K, Rautio A, and Sebert S
Subjects: Adult, Biomarkers blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cohort Studies, Female, Finland, Humans, Inflammation blood, Inflammation diagnosis, Inflammation epidemiology, Male, Risk Factors, Cardiovascular Diseases blood, Copper blood
Abstract: Background: Copper is an abundant trace element in humans where alterations in the circulating concentration could inform on chronic disease aetiology. To date, data are lacking to study how copper may associate with cardiovascular disease (CVD) risk factors in young and healthy population. Molecular evidence suggests an important role of copper in liver metabolism, an essential organ in maintaining cardiovascular health and inflammation, therefore supporting copper as an associated biomarker of the risk., Objective: We performed a cross-sectional analysis to examine the possible associations between blood copper levels and risk factors for CVD and pre-inflammatory process., Design: The data has been collected from a sub-sample set of the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years., Participants: The study included 206 individuals, 116 men and 90 women. To reduce environmental individual variations affecting both copper and the metabolic profile in the study sample, the participants were selected as: i) being born in Finnish Lapland and ii) living in their birth place for the last five years preceding blood sampling., Main Outcome Measures: Fasting blood copper concentration was measured by inductively coupled plasma mass spectrometer. The CVD risk factors included 6 metabolic clusters (30 cardiovascular and pro-inflammatory factors) assessed by nuclear magnetic resonance. Multivariate linear regression analysis was performed to test the linear association between blood copper and 6 metabolic clusters for CVD risk. Associations were assessed under correction for multiple testing., Results: Copper (Cu) levels were comparable in men and women, with no difference between sexes (p-value <0.60). In multiple regression models, sex adjusted, copper was associated with 9 metabolites from 4 metabolic clusters. After adjustment with BMI, copper was associated with 4 metabolites from 3 metabolic clusters: glutamine, beta-hydroxybutyrate, alpha-1-acid glycoprotein (AGP) and high-sensitive C-reactive protein (hs-CRP). After correction for multiple testing, Cu was found positively associated with only 2 biomarkers of inflammation including AGP [p = 0.04] and hs-CRP [p = 0.0001]., Conclusions: Considering the strength and limitation of the study design, the present study does not support evidence for an independent role of copper on biomarkers for CVD risk. Nevertheless, we are reporting a robust association of copper with the inflammatory load that is important to consider in light with the inflammatory component of chronic health. In addition, the association of copper with metabolites may be attributable to BMI or environmental factors associated to it, and warrants further research in large population samples., (Copyright © 2018 Elsevier GmbH. All rights reserved.)
Published: 2019
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42. Hyperemesis gravidarum and cardiometabolic risk factors in adolescents: a follow-up of the Northern Finland Birth Cohort 1986.

Author: Koot MH, Grooten IJ, Sebert S, Koiranen M, Järvelin MR, Kajantie E, Painter RC, and Roseboom TJ
Subjects: Adolescent, Adult, Blood Glucose analysis, Blood Pressure, Body Mass Index, Female, Finland epidemiology, Follow-Up Studies, Humans, Infant, Newborn, Lipids blood, Male, Pregnancy, Pregnancy Outcome epidemiology, Prospective Studies, Risk Factors, Young Adult, Cardiovascular Diseases etiology, Hyperemesis Gravidarum complications, Infant Health statistics & numerical data, Prenatal Exposure Delayed Effects epidemiology
Abstract: Objective: To investigate the long-term consequences of prenatal exposure to maternal hyperemesis gravidarum upon offspring cardiometabolic risk factors., Design: This study is part of the prospective follow-up of the Northern Finland Birth Cohort 1986., Setting: Between 1 July 1985 and 30 June 1986 all pregnant women in two provinces of Finland were recruited at first antenatal visit (99% of eligible participated)., Population: A total of 8953 women with liveborn singleton offspring who consented to having their children followed-up were included., Methods: Hyperemesis gravidarum (HG) was defined as hospitalisation during pregnancy for HG based on the International Classification of Disease (ICD) code. Women who were not hospitalised for HG during pregnancy were used as a reference group. Data on pregnancy and birth outcomes were obtained via medical records and questionnaires; 6462 adolescents, aged 16 years, underwent anthropometric measurements (HG n = 42, reference n = 6420) and 5648 adolescents had a fasting blood sample taken (HG n = 36, reference n = 5612)., Main Outcome Measures: Body mass index (BMI), blood pressure, fasting glucose, and lipid levels in offspring., Results: Multivariate regression analyses showed no differences in offspring BMI (kg/m 2 ; adjusted percentage difference HG versus reference, 2.2; 95% CI -0.1, 4.6), systolic blood pressure (adjusted difference 2.1 mmHg; 95% CI -1.5, 5.6), and fasting blood glucose (mmol/l; adjusted percentage difference, 2.3; 95% CI -0.6, 5.4), between adolescents born to mothers with and without HG., Conclusions: We found no evidence that prenatal exposure to HG has negative consequences for cardiometabolic health of offspring at the age of 16 years., Tweetable Abstract: Hyperemesis gravidarum does not affect cardiometabolic health in adolescent offspring., (© 2017 Royal College of Obstetricians and Gynaecologists.)
Published: 2017
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43. Arsenic, cadmium, lead and mercury levels in blood of Finnish adults and their relation to diet, lifestyle habits and sociodemographic variables.

Author: Abass K, Koiranen M, Mazej D, Tratnik JS, Horvat M, Hakkola J, Järvelin MR, and Rautio A
Subjects: Adult, Feeding Behavior, Female, Finland, Habits, Humans, Male, Middle Aged, Prospective Studies, Selenium blood, Socioeconomic Factors, Surveys and Questionnaires, Arsenic blood, Cadmium blood, Diet, Lead blood, Life Style, Mercury blood
Abstract: The Northern Finland Birth Cohort program (NFBC) is the epidemiological and longitudinal prospective general population research program, which was established to promote health and wellbeing of the population in northern Finland. The aim of present study, as a part of the NFBC program, was to analyze the blood levels of arsenic (B-As), cadmium (B-Cd), lead (B-Pb), total mercury (B-Hg) and selenium (B-Se); to compare these levels with threshold limits; to study sociodemographic factors; and to correlate these levels with calcium and haemoglobin. The study was comprised of 249 NFBC subjects, of which 123 were female and 126 were male (ages 31.1 ± 0.3 and 31.1 ± 0.4, respectively). All participants were asked to complete a questionnaire regarding diet and living habits. The geometric means (± SD) of B-As were 0.49 ± 2.80 μg/l and 0.44 ± 2.72 μg/l; B-Cd were 0.18 ± 4.02 μg/l and 0.12 ± 3.21 μg/l; B-Pb were 17.0 ± 1.8 μg/l and 9.06 ± 2.20 μg/l; B-Hg were 2.18 ± 2.02 μg/l and 1.85 ± 1.78 μg/l; and B-Se were 106.0 ± 1.3 and 94.3 ± 1.3 μg/l in males and females, respectively. Among the subjects in the present analysis, 23 % of males and 17.1 % of females had B-As levels above the ATSDR normal human levels of B-As in unexposed individuals (1.0 μg/l). The B-Pb geometric mean (12.44 μg/l) was approximately one eighth the CDC toxicological cut-off point of 100 μg/l. Twenty-one individuals (8.4 %) exceeded a B-Hg level of 5.8 μg/l. Fifty-eight females (47 %) had a B-Hg higher than 2.0 μg/l, the German Federal Environmental Agency cut-off point for women (18-69 years) who consume fish at least three times/month; therefore, their babies could be at risk of adverse effects during development.
Published: 2017
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44. Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

Author: Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, and Palotie A
Published: 2016
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45. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

Author: Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, and Palotie A
Subjects: Case-Control Studies, Genome-Wide Association Study, Genomics, Humans, Muscle, Smooth metabolism, Vascular Diseases genetics, Genetic Loci genetics, Genetic Markers genetics, Genetic Predisposition to Disease, Migraine Disorders genetics, Polymorphism, Single Nucleotide genetics
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016
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46. Genetic analysis for a shared biological basis between migraine and coronary artery disease.

Author: Winsvold BS, Nelson CP, Malik R, Gormley P, Anttila V, Vander Heiden J, Elliott KS, Jacobsen LM, Palta P, Amin N, de Vries B, Hämäläinen E, Freilinger T, Ikram MA, Kessler T, Koiranen M, Ligthart L, McMahon G, Pedersen LM, Willenborg C, Won HH, Olesen J, Artto V, Assimes TL, Blankenberg S, Boomsma DI, Cherkas L, Davey Smith G, Epstein SE, Erdmann J, Ferrari MD, Göbel H, Hall AS, Jarvelin MR, Kallela M, Kaprio J, Kathiresan S, Lehtimäki T, McPherson R, März W, Nyholt DR, O'Donnell CJ, Quaye L, Rader DJ, Raitakari O, Roberts R, Schunkert H, Schürks M, Stewart AF, Terwindt GM, Thorsteinsdottir U, van den Maagdenberg AM, van Duijn C, Wessman M, Kurth T, Kubisch C, Dichgans M, Chasman DI, Cotsapas C, Zwart JA, Samani NJ, and Palotie A
Abstract: Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD)., Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci., Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP)., Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.
Published: 2015
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47. The association of genotype-based inbreeding coefficient with a range of physical and psychological human traits.

Author: Verweij KJ, Abdellaoui A, Veijola J, Sebert S, Koiranen M, Keller MC, Järvelin MR, and Zietsch BP
Subjects: Adult, Anthropometry, Female, Finland, Homozygote, Humans, Male, Mental Health, Phenotype, Reproduction, Consanguinity, Genetic Fitness physiology, Genetics, Population, Genotype
Abstract: Across animal species, offspring of closely related mates exhibit lower fitness, a phenomenon called inbreeding depression. Inbreeding depression in humans is less well understood because mating between close relatives is generally rare and stigmatised, confounding investigation of its effect on fitness-relevant traits. Recently, the availability of high-density genotype data has enabled quantification of variation in distant inbreeding in 'outbred' human populations, but the low variance of inbreeding detected from genetic data in most outbred populations means large samples are required to test effects, and only a few traits have yet been studied. However, it is likely that isolated populations, or those with a small effective population size, have higher variation in inbreeding and therefore require smaller sample sizes to detect inbreeding effects. With a small effective population size and low immigration, Northern Finland is such a population. We make use of a sample of ∼5,500 'unrelated' individuals in the Northern Finnish Birth Cohort 1966 with known genotypes and measured phenotypes across a range of fitness-relevant physical and psychological traits, including birth length and adult height, body mass index (BMI), waist-to-hip ratio, blood pressure, heart rate, grip strength, educational attainment, income, marital status, handedness, health, and schizotypal features. We find significant associations in the predicted direction between individuals' inbreeding coefficient (measured by proportion of the genome in runs of homozygosity) and eight of the 18 traits investigated, significantly more than the one or two expected by chance. These results are consistent with inbreeding depression effects on a range of human traits, but further research is needed to replicate and test alternative explanations for these effects.
Published: 2014
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48. High prevalence of skin diseases and need for treatment in a middle-aged population. A Northern Finland Birth Cohort 1966 study.

Author: Sinikumpu SP, Huilaja L, Jokelainen J, Koiranen M, Auvinen J, Hägg PM, Wikström E, Timonen M, and Tasanen K
Subjects: Adult, Aged, Cohort Studies, Cross-Sectional Studies, Female, Finland epidemiology, Follow-Up Studies, Health Services Needs and Demand, Humans, Male, Middle Aged, Prevalence, Registries, Risk Factors, Skin Diseases therapy, Skin Diseases epidemiology
Abstract: To determine the overall prevalence of skin diseases a whole-body skin examination was performed for 1,932 members (46-years of age) of the Northern Finland Birth Cohort (NFBC 1966), which is a comprehensive longitudinal research program (N = 12,058). A high prevalence of all skin diseases needing treatment was found (N = 1,158). Half of the cases of skin findings were evaluated to be serious enough to require diagnostic evaluation, treatment or follow-up either in a general health care, occupational health care or a secondary care setting. The remaining half were thought to be slight and self-treatment was advised. Males (70%) had more skin diseases needing treatment than females (52%) (P<0.001). The most common skin finding was a benign skin tumor, which was found in every cohort member. Skin infections (44%), eczemas (27%) and sebaceous gland diseases (27%) were the most common skin diseases in the cohort. Moreover, skin infections and eczemas were more commonly seen in the group with low education compared to those with high education (P<0.005). The results strengthen the postulate that skin diseases are common in an adult population.
Published: 2014
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49. Long-term unemployment is associated with short telomeres in 31-year-old men: an observational study in the northern Finland birth cohort 1966.

Author: Ala-Mursula L, Buxton JL, Ek E, Koiranen M, Taanila A, Blakemore AI, and Järvelin MR
Subjects: Cohort Studies, Finland, Humans, Male, Middle Aged, Socioeconomic Factors, Telomere, Unemployment
Abstract: Objective: Life stress resulting from early-life experiences and domestic stress is linked with shorter leukocyte telomere length (LTL), but evidence on employment-related stress is scarce. We explored whether unemployment in early adulthood is associated with shorter LTL, a potential biomarker of premature aging., Methods: We used data from 5620 men and women belonging to the Northern Finland Birth Cohort 1966. Individually registered unemployment days in 1995-97 were compared with data on biological, behavioral and socioeconomic health predictors and existing medical conditions obtained by surveys and clinical examinations at follow-up in 1997-98. Mean LTL at follow-up was measured by multiplex quantitative real-time PCR. We calculated odds ratios and their 95% confidence intervals (CI) of belonging to the sex-stratified shortest decile of standardized relative mean LTL according to the categories of: 0, <260, <500 and over 500 unemployment days, representing 0, <1, <2 and over 2 calendar years., Results: Among men, unemployment exceeding 500 days during three years was associated with having shorter LTL at follow-up, compared to being continuously employed. The corresponding odds ratio was 2.61 (95% CI 1.16 to 5.85) in the fully adjusted model. Such an association was not found among women in this study., Conclusions: Long-term unemployment in early adulthood is associated with shorter LTL among men.
Published: 2013
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50. Body mass index and overweight in relation to residence distance and population density: experience from the Northern Finland birth cohort 1966.

Author: Näyhä S, Lankila T, Rautio A, Koiranen M, Tammelin TH, Taanila A, Rusanen J, and Laitinen J
Subjects: Activities of Daily Living, Adult, Female, Finland epidemiology, Humans, Male, Prevalence, Surveys and Questionnaires, Body Mass Index, Overweight epidemiology, Population Density, Residence Characteristics
Abstract: Background: The effect of urban sprawl on body weight in Finland is not well known. To provide more information, we examined whether body mass index (BMI) and the prevalence of overweight are associated with an individual's distance to the local community centre and population density in his/her resident area., Methods: The sample consisted of 5363 men and women, members of the Northern Finland Birth Cohort 1966 (NFBC), who filled in a postal questionnaire and attended a medical checkup in 1997, at the age of 31 years. Body mass index (BMI; kg/m(2)) and the prevalence of overweight (BMI ≥ 25.0 kg/m(2)) were regressed on each subject's road distance to the resident commune's centre and on population density in the 1 km(2) geographical grid in which he/she resided, using a generalized additive model. Adjustments were made for sex, marital status, occupational class, education, leisure-time and occupational physical activity, alcohol consumption and smoking., Results: The mean BMI among the subjects was 24.7 kg/m(2), but it increased by increasing road distance (by 1.3 kg/m(2) from 5-10 to 20-184 km) and by decreasing population density (by 1.7 kg/m(2) from 1000-19,192 to 1-5 inhabitants/km(2)). The respective increases in overweight (overall prevalence 41%) were 13 per cent units for distance and 14 per cent units for population density. Adjusted regressions based on continuous explanatory variables showed an inverse L-shaped pattern with a mean BMI of 24.6 kg/m(2) at distances shorter than 5 km and a rise of 2.6 kg/m(2) at longer distances, and an increase of 2.5 kg/m(2) from highest to lowest population density. The associations with road distance were stronger for women than men, while the sex difference in association with population density remained indeterminate., Conclusions: We conclude that young adults in Northern Finland who live far away from local centres or in the most sparsely populated areas are fatter than those who live close to local centres or in densely populated areas. The likely explanations include variations in everyday physical activity in different residential environments, although causality of the associations remains to be confirmed.
Published: 2013
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