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1. Decline in Isotope Dilution Space Ratio Above Age 60 Could Affect Energy Estimates Using the Doubly Labeled Water Method

Author: Wong, William W, Speakman, John R, Ainslie, Philip N, Anderson, Liam J, Arab, Leonore, Baddou, Issad, Bedu-Addo, Kweku, Blaak, Ellen E, Blanc, Stephane, Bonomi, Alberto G, Bouten, Carlijn VC, Bovet, Pascal, Buchowski, Maciej S, Butte, Nancy F, Camps, Stefan G, Casper, Regina, Close, Graeme L, Colbert, Lisa H, Cooper, Jamie A, Das, Sai K, Davies, Peter SW, Eaton, Simon, Ekelund, Ulf, Hambly, Catherine, El Hamdouchi, Asmaa, Entringer, Sonja, Fudge, Barry W, Gillingham, Melanie, Goris, Annelies H, Gurven, Micheal, Hoos, Marije B, Hu, Sumei, Joosen, Annemiek, Katzmarzyk, Peter T, Kempen, Kitty P, Kimura, Misaka, Kraus, William E, Kushner, Robert F, Larsson, Christel L, Morehen, James C, Morton, James P, Neuhouser, Marian L, Nicklas, Theresa A, Ojiambo, Robert M, Pietilainen, Kirsi H, Pitsiladis, Yannis P, Plasqui, Guy, Prentice, Ross L, Rabinovich, Roberto, Racette, Susan B, Raichen, David A, Redman, Leanne, Ravussin, Eric, Reilly, John J, Roberts, Susan, Scuitt, Albertine J, Sjödin, Anders M, Stice, Eric, Urlacher, Samuel S, Valenti, Giulio, van Etten, Ludo M, Van Mil, Edgar A, Verbunt, Jeanine A, Wells, Jonathan CK, Wilson, George, Yoshida, Tsukasa, Zhang, Xueying, Loechl, Cornelia U, Luke, Amy, Murphy-Alford, Alexia J, Pontzer, Herman, Sagayama, Hiroyuki, Rood, Jennifer C, Schoeller, Dale A, Westerterp, Klaas R, and Yamada, Yosuke
Published: 2024
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2. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

Author: Christiansen, Colette, Potier, Louis, Martin, Tiphaine C., Villicaña, Sergio, Castillo-Fernandez, Juan E., Mangino, Massimo, Menni, Cristina, Tsai, Pei-Chien, Campbell, Purdey J., Mullin, Shelby, Ordoñana, Juan R., Monteagudo, Olga, Sachdev, Perminder S., Mather, Karen A., Trollor, Julian N., Pietilainen, Kirsi H., Ollikainen, Miina, Dalgård, Christine, Kyvik, Kirsten, Christensen, Kaare, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Magnusson, Patrik K.E., Pedersen, Nancy L., Wilson, Scott G., Grundberg, Elin, Spector, Tim D., and Bell, Jordana T.
Published: 2024
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3. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author: Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian'an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O'Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh, V, Tatari, Zohreh, Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimaki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietilainen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josee, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., Tobin, Martin, Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian'an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O'Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh, V, Tatari, Zohreh, Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimaki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietilainen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josee, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin
Abstract: Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
Published: 2023
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4. Greater male variability in daily energy expenditure develops through puberty

Author: Halsey, Lewis G., Careau, Vincent, Ainslie, Philip N., Alemán-Mateo, Heliodoro, Andersen, Lene F., Anderson, Liam J., Arab, Leonore, Baddou, Issad, Bandini, Linda, Bedu-Addo, Kweku, Blaak, Ellen E., Blanc, Stephane, Bonomi, Alberto G., Bouten, Carlijn V.C., Bovet, Pascal, Brage, Soren, Buchowski, Maciej S., Butte, Nancy, Camps, Stephan G., Casper, Regian, Close, Graeme L., Colbert, Lisa H., Cooper, Jamie A., Cooper, Richard, Dabare, Prasangi, Das, Sai Krupa, Davies, Peter S.W., Deb, Sanjoy, Nyström, Christine Delisle, Dietz, William, Dugas, Lara R., Eaton, Simon, Ekelund, Ulf, Hamdouchi, Asmaa El, Entringer, Sonja, Forrester, Terrence, Fudge, Barry W., Gillingham, Melanie, Goris, Annelies H., Gurven, Michael, Haisma, Hinke, Hambly, Catherine, Hoffman, Daniel, Hoos, Marije B., Hu, Sumei, Joonas, Noorjehan, Joosen, Annemiek, Katzmarzyk, Peter, Kempen, Kitty P., Kimura, Misaka, Kraus, William E., Kriengsinyos, Wantanee, Kuriyan, Rebecca, Kushner, Robert F., Lambert, Estelle V., Lanerolle, Pulani, Larsson, Christel L., Lessan, Nader, Löf, Marie, Martin, Corby, Matsiko, Eric, Meijer, Gerwin A., Morehen, James C., Morton, James P., Must, Aviva, Neuheuser, Marian, Nicklas, Theresa A., Ojiambo, Robert M., Pietilainen, Kirsi H., Pitsiladis, Yannis P., Plange-Rhule, Jacob, Plasqui, Guy, Prentice, Ross L., Rabinovich, Roberto, Racette, Susan B., Raichen, David A., Ravussin, Eric, Redman, Leanne, Reilly, John J., Reynolds, Rebecca, Roberts, Susan, Rood, Jennifer C., Samaranayake, Dulani, Sardinha, Luís B., Scuitt, Albertine J., Silva, Analiza M., Sinha, Srishti, Sjödin, Anders M., Stice, Eric, Stunkard, Albert, Urlacher, Samuel S., Valencia, Mauro Eduardo, Valenti, Giulio, Van Etten, Ludo M., Van Mil, Edgar A., Verbunt, Jeanine A., Wells, Jonathan C.K., Wilson, George, Wood, Brian, Yoshida, Tsukasa, Zhang, Xueying, Murphy-Alford, Alexia, Loechl, Cornelia, Luke, Amy, Pontzer, Herman, Rood, Jennifer, Sagayama, Hiroyuki, Westerterp, Klaas R., Wong, William W., Yamada, Yosuke, Speakman, John R., Halsey, Lewis G., Careau, Vincent, Ainslie, Philip N., Alemán-Mateo, Heliodoro, Andersen, Lene F., Anderson, Liam J., Arab, Leonore, Baddou, Issad, Bandini, Linda, Bedu-Addo, Kweku, Blaak, Ellen E., Blanc, Stephane, Bonomi, Alberto G., Bouten, Carlijn V.C., Bovet, Pascal, Brage, Soren, Buchowski, Maciej S., Butte, Nancy, Camps, Stephan G., Casper, Regian, Close, Graeme L., Colbert, Lisa H., Cooper, Jamie A., Cooper, Richard, Dabare, Prasangi, Das, Sai Krupa, Davies, Peter S.W., Deb, Sanjoy, Nyström, Christine Delisle, Dietz, William, Dugas, Lara R., Eaton, Simon, Ekelund, Ulf, Hamdouchi, Asmaa El, Entringer, Sonja, Forrester, Terrence, Fudge, Barry W., Gillingham, Melanie, Goris, Annelies H., Gurven, Michael, Haisma, Hinke, Hambly, Catherine, Hoffman, Daniel, Hoos, Marije B., Hu, Sumei, Joonas, Noorjehan, Joosen, Annemiek, Katzmarzyk, Peter, Kempen, Kitty P., Kimura, Misaka, Kraus, William E., Kriengsinyos, Wantanee, Kuriyan, Rebecca, Kushner, Robert F., Lambert, Estelle V., Lanerolle, Pulani, Larsson, Christel L., Lessan, Nader, Löf, Marie, Martin, Corby, Matsiko, Eric, Meijer, Gerwin A., Morehen, James C., Morton, James P., Must, Aviva, Neuheuser, Marian, Nicklas, Theresa A., Ojiambo, Robert M., Pietilainen, Kirsi H., Pitsiladis, Yannis P., Plange-Rhule, Jacob, Plasqui, Guy, Prentice, Ross L., Rabinovich, Roberto, Racette, Susan B., Raichen, David A., Ravussin, Eric, Redman, Leanne, Reilly, John J., Reynolds, Rebecca, Roberts, Susan, Rood, Jennifer C., Samaranayake, Dulani, Sardinha, Luís B., Scuitt, Albertine J., Silva, Analiza M., Sinha, Srishti, Sjödin, Anders M., Stice, Eric, Stunkard, Albert, Urlacher, Samuel S., Valencia, Mauro Eduardo, Valenti, Giulio, Van Etten, Ludo M., Van Mil, Edgar A., Verbunt, Jeanine A., Wells, Jonathan C.K., Wilson, George, Wood, Brian, Yoshida, Tsukasa, Zhang, Xueying, Murphy-Alford, Alexia, Loechl, Cornelia, Luke, Amy, Pontzer, Herman, Rood, Jennifer, Sagayama, Hiroyuki, Westerterp, Klaas R., Wong, William W., Yamada, Yosuke, and Speakman, John R.
Abstract: There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.
Published: 2023

5. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

Author: Surakka, Ida, Whitfield, John B, Perola, Markus, Visscher, Peter M, Montgomery, Grant W, Falchi, Mario, Willemsen, Gonneke, de Geus, Eco JC, Magnusson, Patrik KE, Christensen, Kaare, Sorensen, Thorkild IA, Pietilainen, Kirsi H, Rantanen, Taina, Silander, Kaisa, Widen, Elisabeth, Muilu, Juha, Rahman, Iffat, Liljedahl, Ulrika, Syvanen, Ann-Christine, Palotie, Aarno, Kaprio, Jaakko, Kyvik, Kirsten O, Pedersen, Nancy L, Boomsma, Dorret I, Spector, Tim, Martin, Nicholas G, Ripatti, Samuli, and Peltonen, Leena
Published: 2012

6. Twin Study of Heritability of Eating Bread in Danish and Finnish Men and Women

Author: Hasselbalch, Ann L, Silventoinen, Karri, Keskitalo, Kaisu, Pietilainen, Kirsi H, Rissanen, Aila, Heitmann, Berit L, Kyvik, Kirsten O, Sorensen, Thorkild IA, and Kaprio, Jaakko
Published: 2010

7. Improving the Accuracy of Self-reports on Diet and Physical Exercise: The Co-twin Control Method

Author: Pietilainen, Kirsi H, Rissanen, Aila, Kaprio, Jaakko, and Bogl, Leonie H
Published: 2009

8. Effects of 32-Year Leisure Time Physical Activity Discordance in Twin Pairs on Health (TWINACTIVE Study): Aims, Design and Results for Physical Fitness

Author: Leskinen, Tuija, Waller, Katja, Mutikainen, Sara, Aaltonen, Sari, Ronkainen, Paula HA, Alen, Markku, Sipila, Sarianna, Kovanen, Vuokko, Perhonen, Merja, Pietilainen, Kirsi H, Cheng, Sulin, Suominen, Harri, Kainulainen, Heikki, Kaprio, Jaakko, and Kujala, Urho M
Published: 2009

9. Growth Patterns in Young Adult Monozygotic Twin Pairs Discordant and Concordant for Obesity

Author: Pietilainen, Kirsi H, Rissanen, Aila, Laamanen, Maria, Lindholm, Anna-Kaisa, Markkula, Harri, Yki-Jarvinen, Hannele, and Kaprio, Jaakko
Published: 2004

10. Sex Differences in Heritability of BMI: A Comparative Study of Results from Twin Studies in Eight Countries

Author: Schousboe, Karoline, Willemsen, Gonneke, Kyvik, Kristen O, Mortensen, Jakob, Boomsma, Dorret I, Cornes, Belinda K, Davis, Chayna J, Fagnani, Corrado, Hjelmborg, Jacob, Kaprio, Jaakko, de Lange, Marlies, Luciano, Michelle, Martin, Nicholas G, Pedersen, Nancy, Pietilainen, Kirsi H, Rissanen, Aila, Saarni, Suoma, Sorensen, Thorkild IA, van Baal, GCaroline M, and Harris, Jennifer R
Published: 2003

11. Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity

Author: Mustelin, Linda, Pietilainen, Kirsi H., Rissanen, Aila, Sovijarvi, Anssi R., Piirila, Paivi, Naukkarinen, Jussi, Peltonen, Leena, Kaprio, Jaakko, and Yki-Jarvinen, Hannele
Subjects: Gene expression -- Physiological aspects, Gene expression -- Research, Obesity -- Risk factors, Obesity -- Genetic aspects, Obesity -- Control, Obesity -- Research, Oxidative phosphorylation -- Physiological aspects, Oxidative phosphorylation -- Genetic aspects, Oxidative phosphorylation -- Research, Biological sciences
Abstract: Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defects can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 [+ or -] 1.8 kg/[m.sup.2]) and 10 concordant (1.0 [+ or -] 0.7 kg/[m.sup.2]) monozygotic (MZ) twin pairs aged 24-27 yr were identified among 658 MZ pairs in the population-based FinnTwin 16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake (V[o.sub.2max]) and working capacity ([W.sub.max]) using a bicycle ergometer exercise test with gas exchange analysis. The obese cotwins had lower insulin sensitivity than their nonobese counterparts (M value 6.1 [+ or -] 2.0 vs. 9.2 [+ or -] 3.2 mg * kg LB[M.sup.-1] * [min.sup.-1], P < 0.01). Transcript levels of genes involved in the oxidative phosphorylation pathway (GO:0006119) in adipose tissue were lower (P < 0.05) in the obese compared with the nonobese cotwins. The obese cotwins were also less fit, as measured by V[o.sub.2max] (50.6 [+ or -] 6.5 vs. 54.2 [+ or -] 6.4 ml * kg LB[M.sup.-1] * [min.sup.-1], for obese vs. nonobese, P < 0.05), [W.sub.max] (3.9 [+ or -] 0.5 vs. 4.4 [+ or -] 0.7 W/kg LBM, P < 0.01) and also less active, by the Baecke leisure time physical activity index (2.8 [+ or -] 0.5 vs. 3.3 [+ or -] 0.6, P < 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria. body composition; cardiorespiratory fitness; spiroergometry; gene expression
Published: 2008

12. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity

Author: Pietilainen, Kirsi H., Naukkarinen, Jussi, Rissanen, Aila, Saharinen, Juha, Ellonen, Pekka, Keranen, Heli, Suomalainen, Anu, Gotz, Alexandra, Suortti, Tapani, Yki-Jarvinen, Hannele, Oresic, Matej, Kaprio, Jaakko, and Peltonen, Leena
Abstract: Introduction Adipose tissue is a key player in obesity-related metabolic dysfunctions, and is closely linked to other peripheral organs that control energy flux [1]. To understand the pathogenesis of adipose [...], Background The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background. Methods and Findings We used a special study design of 'clonal controls,' rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean ± standard deviation (SD) age 25.8 ± 1.4 y and a body mass index (BMI) difference 5.2 ± 1.8 kg/[m.sup.2]. Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults. Conclusions Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance. doi:10.1371/journal.pmed.0050051
Published: 2008

13. Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial

Author: Navas-Carretero, Santiago, San-Cristobal, Rodrigo, Vestentoft, Pia Siig, Brand-Miller, Jennie C., Jalo, Elli, Westerterp-Plantenga, Margriet, Simpson, Elizabeth J., Handjieva-Darlenska, Teodora, Stratton, Gareth, Huttunen-Lenz, Maija, Lam, Tony, Muirhead, Roslyn, Poppitt, Sally, Pietilainen, Kirsi H., Adam, Tanja, Taylor, Moira A., Handjiev, Svetoslav, McNarry, Melitta A., Hansen, Sylvia, Brodie, Shannon, Silvestre, Marta P., Macdonald, Ian A., Boyadjieva, Nadka, Mackintosh, Kelly A., Schlicht, Wolfgang, Liu, Amy, Larsen, Thomas M., Fogelholm, Mikael, Raben, Anne, Alfredo Martinez, J., Navas-Carretero, Santiago, San-Cristobal, Rodrigo, Vestentoft, Pia Siig, Brand-Miller, Jennie C., Jalo, Elli, Westerterp-Plantenga, Margriet, Simpson, Elizabeth J., Handjieva-Darlenska, Teodora, Stratton, Gareth, Huttunen-Lenz, Maija, Lam, Tony, Muirhead, Roslyn, Poppitt, Sally, Pietilainen, Kirsi H., Adam, Tanja, Taylor, Moira A., Handjiev, Svetoslav, McNarry, Melitta A., Hansen, Sylvia, Brodie, Shannon, Silvestre, Marta P., Macdonald, Ian A., Boyadjieva, Nadka, Mackintosh, Kelly A., Schlicht, Wolfgang, Liu, Amy, Larsen, Thomas M., Fogelholm, Mikael, Raben, Anne, and Alfredo Martinez, J.
Abstract: Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) x fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs. Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve >= 8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures. Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activit
Published: 2021

14. Molecular pathways behind acquired obesity : Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI

Author: van der Kolk, Birgitta W., Saari, Sina, Lovric, Alen, Arif, Muhammad, Alvarez, Marcus, Ko, Arthur, Miao, Zong, Sahebekhtiari, Navid, Muniandy, Maheswary, Heinonen, Sini, Oghabian, Ali, Jokinen, Riikka, Jukarainen, Sakari, Hakkarainen, Antti, Lundbom, Jesper, Kuula, Juho, Groop, Per-Henrik, Tukiainen, Taru, Lundbom, Nina, Rissanen, Aila, Kaprio, Jaakko, Williams, Evan G., Zamboni, Nicola, Mardinoglu, Adil, Pajukanta, Paivi, Pietilainen, Kirsi H., van der Kolk, Birgitta W., Saari, Sina, Lovric, Alen, Arif, Muhammad, Alvarez, Marcus, Ko, Arthur, Miao, Zong, Sahebekhtiari, Navid, Muniandy, Maheswary, Heinonen, Sini, Oghabian, Ali, Jokinen, Riikka, Jukarainen, Sakari, Hakkarainen, Antti, Lundbom, Jesper, Kuula, Juho, Groop, Per-Henrik, Tukiainen, Taru, Lundbom, Nina, Rissanen, Aila, Kaprio, Jaakko, Williams, Evan G., Zamboni, Nicola, Mardinoglu, Adil, Pajukanta, Paivi, and Pietilainen, Kirsi H.
Abstract: Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity., QC 20210524
Published: 2021
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15. GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance

Author: Matikainen, Niina, Bogl, Leonie H., Hakkarainen, Antti, Lundbom, Jesper, Lundbom, Nina, Kaprio, Jaakko, Rissanen, Aila, Holst, Jens J., and Pietilainen, Kirsi H.
Subjects: University of Helsinki, Diagnosis, Care and treatment, Analysis, Diabetes mellitus -- Diagnosis -- Care and treatment, Glucose tolerance test, Insulin resistance -- Analysis, Glucose tolerance tests, Diabetes -- Diagnosis -- Care and treatment
Abstract: OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We [...]
Published: 2014
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16. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation

Author: Lassenius, Mariann I., Pietilainen, Kirsi H., Kaartinen, Kati, Pussinen, Pirkko J., Syrjanen, Jaana, Forsblom, Carol, Porsti, Ilkka, Rissanen, Aila, Kaprio, Jaakko, Mustonen, Jukka, Groop, Per-Henrik, and Lehto, Markku
Subjects: European Association for the Study of Diabetes, Development and progression, Research, Obesity -- Research -- Development and progression, Inflammation -- Research -- Development and progression, Mitogens, Albumin, Medical research, Immunoglobulin A, Insulin resistance -- Research -- Development and progression, Cholesterol, Kidney diseases -- Research -- Development and progression, Type 1 diabetes -- Research -- Development and progression, Medicine, Experimental
Abstract: OBJECTIVE--To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney [...]
Published: 2011
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17. Modification effects of physical activity and protein intake on heritability of body size and composition

Author: Silventoinen, Karri, Hasselbalch, Ann Louise, Lallukka, Tea, Bogl, Leonie, Pietilainen, Kirsi H., Heitmann, Berit L., Schousboe, Karoline, Rissanen, Aila, Kyvik, Kirsten O., Sorensen, Thorkild I.A., and Kaprio, Jaakko
Subjects: Exercise -- Health aspects, High-protein diet -- Health aspects, Obesity -- Risk factors, Obesity -- Development and progression, Obesity -- Genetic aspects, Food/cooking/nutrition, Health
Abstract: Background: The development of obesity is still a poorly understood process that is dependent on both genetic and environmental factors. Objective: The objective was to examine how physical activity and the proportion of energy as protein in the diet modify the genetic variation of body mass index (BMI), waist circumference, and percentage body fat. Design: Twins from Denmark (756 complete pairs) and Finland (278 complete pairs) aged 18-67 and 21-24 y, respectively, participated. The proportion of energy as protein in the diet was estimated by using food-frequency questionnaires. The participants reported the frequency and intensity of their leisure time physical activity. Waist circumference and BMI were measured. Percentage body fat was assessed in Denmark by using a bioelectrical impedance method. The data were analyzed by using gene-environment interaction models for twin data with the Mx statistical package (Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA). Results: High physical activity was associated with lower mean values, and a high proportion of protein in the diet was associated with higher mean BMI, waist circumference, and percentage body fat and a reduction in genetic and environmental variances. Genetic modification by physical activity was statistically significant for BMI (-0.18; 95% CI: -0.31, -0.05) and waist circumference (-0.14; 95% CI: -0.22, -0.05) in the merged data. A high proportion of protein in the diet reduced genetic and environmental variances in BMI and waist circumference in Danish men but not in women of in Finnish men. Conclusions: Our results suggest that, in physically active individuals, the genetic variation in weight is reduced, which possibly suggests that physical activity is able to modify the action of the genes responsible for predisposition to obesity, whereas the protein content of the diet has no appreciable effect.
Published: 2009

18. Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity-A Study on Rare BMI-Discordant Monozygotic Twin Pairs

Author: Sahebekhtiari, Navid, Saraswat, Mayank, Joenvaara, Sakari, Jokinen, Riikka, Lovric, Alen, Kaye, Sanna, Mardinoglu, Adil, Rissanen, Aila, Kaprio, Jaakko, Renkonen, Risto, Pietilainen, Kirsi H., Sahebekhtiari, Navid, Saraswat, Mayank, Joenvaara, Sakari, Jokinen, Riikka, Lovric, Alen, Kaye, Sanna, Mardinoglu, Adil, Rissanen, Aila, Kaprio, Jaakko, Renkonen, Risto, and Pietilainen, Kirsi H.
Abstract: Purpose: The purpose of this study is to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation. Experimental Design: The effect of excess body weight is assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg m−2, n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat is interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy. Results: Seventy-five proteins are differentially expressed, with significant enrichment for complement and inflammatory response pathways in the heavier co-twins. The complement dysregulation is found in obesity in both the liver fat subgroups. The complement and inflammatory proteins are significantly associated with adiposity measures, insulin resistance and impaired lipids. Conclusions and Clinical Relevance: The early pathophysiological mechanisms in obesity are incompletely understood. It is shown that aberrant complement regulation in plasma is present in very early stages of clinically healthy obese persons, independently of liver fat and in the absence of genetic variation that typically confounds human studies., QC 20190813
Published: 2019
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19. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change

Author: Wurtz, Peter, Wang, Qin, Kangas, Antti J., Richmond, Rebecca C., Skarp, Joni, Tiainen, Mika, Tynkkynen, Tuulia, Soininen, Pasi, Havulinna, Aki S., Kaakinen, Marika, Viikari, Jorma S., Savolainen, Markku J., Kahonen, Mika, Lehtimaki, Terho, Mannisto, Satu, Blankenberg, Stefan, Zeller, Tanja, Laitinen, Jaana, Pouta, Anneli, Mantyselka, Pekka, Vanhala, Mauno, Elliott, Paul, Pietilainen, Kirsi H., Ripatti, Samuli, Salomaa, Veikko, Raitakari, Olli T., Jarvelin, Marjo-Riitta, Smith, George Davey, and Ala-Korpela, Mika
Subjects: Health aspects, Body weight -- Health aspects, Adipose tissue -- Health aspects, Adipose tissues -- Health aspects
Abstract: Introduction The prevalence of overweight and obesity has reached epidemic proportions and represents a major threat to public health worldwide [1,2]. Excess body weight, as assessed by body mass index [...], Background: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. Methodsand Findings: We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/[m.sup.2]). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p < 0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% [+ or -] 3%; [R.sup.2] = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p < 0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation- related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the crosssectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; [R.sup.2] = 0.92). Conclusions: Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
Published: 2014
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20. Genes and Environment in the Tracking of Body Size from Birth to Late Adolescence

Author: Pietilainen, Kirsi H, Kaprio, Jaakko, Rasanen, Maija, Winter, Torsten, Rissanen, Aila, and Rose, Richard J
Published: 2001

21. Adipose tissue NAD(+)-homeostasis, sirtuins and poly(ADP-ribose) polymerases - important players in mitochondrial metabolism and metabolic health

Author: Jokinen, Riikka, Pirnes-Karhu, Sini, Pietilainen, Kirsi H., Pirinen, Eija, Research Programs Unit, University of Helsinki, Diabetes and Obesity Research Program, Research Programme for Molecular Neurology, Clinicum, Institute for Molecular Medicine Finland, Department of Medicine, Endokrinologian yksikkö, Eija Pirinen / Principal Investigator, and HUS Abdominal Center
Subjects: HIGH-FAT DIET, INSULIN SENSITIVITY, Poly(ADP-ribose) polymerases, INDUCED OBESITY, ENERGY-EXPENDITURE, Adipose tissue, NICOTINAMIDE MONONUCLEOTIDE, Mitochondria, BROWN FAT, 3121 General medicine, internal medicine and other clinical medicine, CALORIE RESTRICTION, Sirtuins, LOW SIRT1 EXPRESSION, Obesity, NAD(+), MEDIATED NAD(+) BIOSYNTHESIS, PPAR-GAMMA ACTIVITY
Abstract: Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions. The mitochondrial processes are dependent on the proper NAD(+)/NADH redox balance and NAD+ is essential for reactions catalyzed by the key regulators of mitochondrial metabolism, sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs). Notably, obesity is associated with disturbed adipose tissue NAD(+) homeostasis and the balance of SIRT and PARP activities. In this review we aim to summarize existing literature on the maintenance of intracellular NAD(+) pools and the function of SIRTs and PARPs in adipose tissue during normal and obese conditions, with the purpose of comprehending their potential role in mitochondrial derangements and obesity associated metabolic complications. Understanding the molecular mechanisms that are the root cause of the adipose tissue mitochondrial derangements is crucial for developing new effective strategies to reverse obesity associated metabolic complications.
Published: 2017

22. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans

Author: Mardinoglu, Adil, Wu, Hao, Björnson, Elias, Zhang, Cheng, Hakkarainen, Antti, Rasanen, Sari M., Lee, Sunjae, Mancina, Rosellina M., Bergentall, Mattias, Pietilainen, Kirsi H., Söderlund, Sanni, Matikainen, Niina, Stahlman, Marcus, Bergh, Per-Olof, Adiels, Martin, Piening, Brian D., Graner, Marit, Lundbom, Nina, Williams, Kevin J., Romeo, Stefano, Nielsen, Jens, Snyder, Michael, Uhlén, Mathias, Bergström, Göran, Perkins, Rosie, Marschall, Hanns-Ulrich, Backhed, Fredrik, Taskinen, Marja-Riitta, Boren, Jan, Mardinoglu, Adil, Wu, Hao, Björnson, Elias, Zhang, Cheng, Hakkarainen, Antti, Rasanen, Sari M., Lee, Sunjae, Mancina, Rosellina M., Bergentall, Mattias, Pietilainen, Kirsi H., Söderlund, Sanni, Matikainen, Niina, Stahlman, Marcus, Bergh, Per-Olof, Adiels, Martin, Piening, Brian D., Graner, Marit, Lundbom, Nina, Williams, Kevin J., Romeo, Stefano, Nielsen, Jens, Snyder, Michael, Uhlén, Mathias, Bergström, Göran, Perkins, Rosie, Marschall, Hanns-Ulrich, Backhed, Fredrik, Taskinen, Marja-Riitta, and Boren, Jan
Abstract: A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD., QC 20180404
Published: 2018
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23. Associations Between Birth Size and Later Height From Infancy Through Adulthood: an Individual Based Pooled Analysis of 28 Twin Cohorts Participating in the Codatwins Project

Author: Fisiología, Fisiologia, Jelenkovic Moreno, Aline, Yokoyama, Yoshie, Sund, Reijo, Hur, Yoon-Mi, Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas Sevenius, Ooki, Syuichi, Ullemar, Vilhelmina, Almqvisth, Catarina, Magnusson, Patrik K. E., Saudino, Kimberly J., Stazi, Maria A., Fagnani, Corrado, Brescianini, Sonia, Nelson, Tracy L., Whitfield, Keith E., Knafo Noam, Ariel, Mankuta, David, Abramson, Lior, Cutler, Tessa L., Hopper, John L., Llewellyn, Clare H., Fisher, Abigail, Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Bjerregaard Andersen, Morten, Nielsen, Henning Beck, Sodemann, Morten, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Burt, S. Alexandra, Klump, Kelly L., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Willemsen, Gonneke, Bartels, Meike, Van Beijsterveld, Catharina E. M., Craig, Jeffrey M., Saffery, Richard, Rasmussen, Finn, Tynelius, Per, Heikkila, Kauko, Pietilainen, Kirsi H., Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Haworth, Claire M. A., Plomin, Robert, Ji, Fuling, Ning, Feng, Pang, Zengchang, Rebato Ochoa, Esther Matilde, Tarnoki, Adam D., Tarnoki, David L., Kim, Jina, Lee, Jooyeon, Lee, Sooji, Sung, Joohon, Loos, Ruth J. F., Boomsma, Dorret I., Sorensen, Thorkild I. A., Kaprio, Jaakko, Silventoinen, Karri, Fisiología, Fisiologia, Jelenkovic Moreno, Aline, Yokoyama, Yoshie, Sund, Reijo, Hur, Yoon-Mi, Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas Sevenius, Ooki, Syuichi, Ullemar, Vilhelmina, Almqvisth, Catarina, Magnusson, Patrik K. E., Saudino, Kimberly J., Stazi, Maria A., Fagnani, Corrado, Brescianini, Sonia, Nelson, Tracy L., Whitfield, Keith E., Knafo Noam, Ariel, Mankuta, David, Abramson, Lior, Cutler, Tessa L., Hopper, John L., Llewellyn, Clare H., Fisher, Abigail, Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Bjerregaard Andersen, Morten, Nielsen, Henning Beck, Sodemann, Morten, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Burt, S. Alexandra, Klump, Kelly L., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Willemsen, Gonneke, Bartels, Meike, Van Beijsterveld, Catharina E. M., Craig, Jeffrey M., Saffery, Richard, Rasmussen, Finn, Tynelius, Per, Heikkila, Kauko, Pietilainen, Kirsi H., Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Haworth, Claire M. A., Plomin, Robert, Ji, Fuling, Ning, Feng, Pang, Zengchang, Rebato Ochoa, Esther Matilde, Tarnoki, Adam D., Tarnoki, David L., Kim, Jina, Lee, Jooyeon, Lee, Sooji, Sung, Joohon, Loos, Ruth J. F., Boomsma, Dorret I., Sorensen, Thorkild I. A., Kaprio, Jaakko, and Silventoinen, Karri
Abstract: Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14-4.25 cm and 0.18-0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
Published: 2018

24. Genetic and environmental factors affecting birth size variation:a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts

Author: Yokoyama, Yoshie, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Fagnani, Corrado, Stazi, Maria A., Brescianini, Sonia, Ji, Fuling, Ning, Feng, Pang, Zengchang, Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Rebato, Esther, Hopper, John L., Cutler, Tessa L., Saudino, Kimberly J., Nelson, Tracy L., Whitfield, Keith E., Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Llewellyn, Clare H., Fisher, Abigail, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Bartels, Meike, van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas S., Craig, Jeffrey M., Saffery, Richard, Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Haworth, Claire M. A., Plomin, Robert, Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Rasmussen, Finn, Tynelius, Per, Tarnoki, Adam D., Tarnoki, David L., Ooki, Syuichi, Rose, Richard J., Pietilainen, Kirsi H., Sørensen, Thorkild I. A., Boomsma, Dorret I., Kaprio, Jaakko, Silventoinen, Karri, Yokoyama, Yoshie, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Fagnani, Corrado, Stazi, Maria A., Brescianini, Sonia, Ji, Fuling, Ning, Feng, Pang, Zengchang, Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Rebato, Esther, Hopper, John L., Cutler, Tessa L., Saudino, Kimberly J., Nelson, Tracy L., Whitfield, Keith E., Corley, Robin P., Huibregtse, Brooke M., Derom, Catherine A., Vlietinck, Robert F., Loos, Ruth J. F., Llewellyn, Clare H., Fisher, Abigail, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Bartels, Meike, van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, Harris, Jennifer R., Brandt, Ingunn, Nilsen, Thomas S., Craig, Jeffrey M., Saffery, Richard, Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Haworth, Claire M. A., Plomin, Robert, Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Rasmussen, Finn, Tynelius, Per, Tarnoki, Adam D., Tarnoki, David L., Ooki, Syuichi, Rose, Richard J., Pietilainen, Kirsi H., Sørensen, Thorkild I. A., Boomsma, Dorret I., Kaprio, Jaakko, and Silventoinen, Karri
Published: 2018

25. Birth size and gestational age in opposite-sex twins as compared to same-sex twins:An individual-based pooled analysis of 21 cohorts

Author: Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Hur, Yoon-Mi, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Bogl, Leonie H., Pietilainen, Kirsi H., Vuoksimaa, Eero, Ji, Fuling, Ning, Feng, Pang, Zengchang, Nelson, Tracy L., Whitfield, Keith E., Rebato, Esther, Llewellyn, Clare H., Fisher, Abigail, Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Tarnoki, Adam D., Tarnoki, David L., Ooki, Syuichi, Stazi, Maria A., Fagnani, Corrado, Brescianini, Sonia, Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Cutler, Tessa L., Hopper, John L., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Craig, Jeffrey M., Saffery, Richard, Haworth, Claire M. A., Plomin, Robert, Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Burt, S. Alexandra, Klump, Kelly L., Vlietinck, Robert F., Derom, Catherine A., Loos, Ruth J. F., Boomsma, Dorret I., Sorensen, Thorkild I.A., Kaprio, Jaakko, Silventoinen, Karri, Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Hur, Yoon-Mi, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Bogl, Leonie H., Pietilainen, Kirsi H., Vuoksimaa, Eero, Ji, Fuling, Ning, Feng, Pang, Zengchang, Nelson, Tracy L., Whitfield, Keith E., Rebato, Esther, Llewellyn, Clare H., Fisher, Abigail, Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Tarnoki, Adam D., Tarnoki, David L., Ooki, Syuichi, Stazi, Maria A., Fagnani, Corrado, Brescianini, Sonia, Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Cutler, Tessa L., Hopper, John L., Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Craig, Jeffrey M., Saffery, Richard, Haworth, Claire M. A., Plomin, Robert, Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Burt, S. Alexandra, Klump, Kelly L., Vlietinck, Robert F., Derom, Catherine A., Loos, Ruth J. F., Boomsma, Dorret I., Sorensen, Thorkild I.A., Kaprio, Jaakko, and Silventoinen, Karri
Abstract: It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.
Published: 2018

26. Does The Sex Of One'S Co-Twin Affect Height And Bmi In Adulthood? A Study Of Dizygotic Adult Twins From 31 Cohorts

Author: Bogl, Leonie H., Jelenkovic, Aline, Vuoksimaa, Eero, Ahrenfeldt, Linda, Pietilainen, Kirsi H., Stazi, Maria A., Fagnani, Corrado, D'Ippolito, Cristina, Hur, Yoon-Mi, Jeong, Hoe-Uk, Silberg, Judy L., Eaves, Lindon J., Maes, Hermine H., Bayasgalan, Gombojav, Narandalai, Danshiitsoodol, Cutler, Tessa L., Kandler, Christian, Jang, Kerry L., Christensen, Kaare, and Skytthe, Axel
Abstract: Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs.
Published: 2017

27. Genetic regulation of growth from birth to 18 years of age: the Swedish young male twins study

Author: Silventoinen, Karri, Pietilainen, Kirsi H., Tynelius, Per, Sorensen, Thorkild I.A., Kaprio, Jaakko, and Rasmussen, Finn
Subjects: Growth -- Genetic aspects, Growth -- Environmental aspects, Twins -- Growth, Twins -- Genetic aspects, Company growth, Biological sciences
Abstract: Swedish male twin pairs are studied to explain the impact of genetic and environmental factors on the growth from birth to 18 years of age. The correlation between growth and the genetic factors is shown to become stronger with the age.
Published: 2008

28. Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity : a study of young healthy MZ twins

Author: Heinonen, Sini, Muniandy, Maheswary, Buzkova, Jana, Mardinoglu, Adil, Rodriguez, Amaia, Fruhbeck, Gema, Hakkarainen, Antti, Lundbom, Jesper, Lundbom, Nina, Kaprio, Jaakko, Rissanen, Aila, Pietilainen, Kirsi H., Heinonen, Sini, Muniandy, Maheswary, Buzkova, Jana, Mardinoglu, Adil, Rodriguez, Amaia, Fruhbeck, Gema, Hakkarainen, Antti, Lundbom, Jesper, Lundbom, Nina, Kaprio, Jaakko, Rissanen, Aila, and Pietilainen, Kirsi H.
Abstract: Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae 3 kg/m(2)) and concordant (n = 5, Delta BMI < 3 kg/m(2)) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins. Abdominal body fat distribution (MRI), liver fat content (magnetic resonance spectroscopy), insulin sensitivity (OGTT), high-sensitivity C-reactive protein, serum lipids and adipokines were measured. Subcutaneous abdominal adipose tissue biopsies were obtained to analyse the transcriptomics patterns of the isolated adipocytes as well as of the whole adipose tissue. Mitochondrial DNA transcript levels in adipocytes were measured by quantitative real-time PCR. Western blots of oxidative phosphorylation (OXPHOS) protein levels in adipocytes were performed in obese and lean unrelated individuals. The heavier (BMI 29.9 +/- 1.0 kg/m(2)) co-twins of the discordant twin pairs had more subcutaneous, intra-abdominal and liver fat and were more insulin resistant (p < 0.01 for all measures) than the lighter (24.1 +/- 0.9 kg/m(2)) co-twins. Altogether, 2538 genes in adipocytes and 2135 in adipose tissue were significantly differentially expressed (nominal p < 0.05) between the co-twins. Pathway analysis of these transcripts in both isolated adipocytes and adipose tissue revealed that the heavier co-twins displayed reduced expression of genes relating to mitochondrial pathways, a result that was replicated when analysing the pathways behind the most consistently downregulated genes in the heavier co-twins (in at least 12 out of 14 pairs). Consistently upregulated genes in adipocytes were related to inflammation. We confirmed that mitochondrial DNA transcript levels (12S RNA, 16S RNA, COX1, QC 20170123
Published: 2017
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29. Telomere length in circulating leukocytes is associated with lung function and disease

Author: Albrecht, Eva, Sillanpaa, Elina, Karrasch, Stefan, Alves, Alexessander Couto, Codd, Veryan, Hovatta, Iiris, Buxton, Jessica L., Nelson, Christopher P., Broer, Linda, Hägg, Sara, Mangino, Massimo, Willemsen, Gonneke, Surakka, Ida, Ferreira, Manuel A. R., Amin, Najaf, Oostra, Ben A., Backmand, Hell M., Peltonen, Markku, Sarna, Seppo, Rantanen, Taina, Sipila, Sarianna, Korhonen, Tellervo, Madden, Pamela A. F., Gieger, Christian, Jorres, Rudolf A., Heinrich, Joachim, Behr, Juergen, Huber, Rudolf M., Peters, Annette, Strauch, Konstantin, Wichmann, H. Erich, Waldenberger, Melanie, Blakemore, Alexandra I. F., de Geus, Eco J. C., Nyholt, Dale R., Henders, Anjali K., Piirila, Paeivi L., Rissanen, Aila, Magnusson, Patrik K. E., Vinuela, Ana, Pietilainen, Kirsi H., Martin, Nicholas G., Pedersen, Nancy L., Boomsma, Dorret I., Spector, Tim D., van Duijn, Cornelia M., Kaprio, Jaakko, Samani, Nilesh J., Jarvelin, Marjo-Riitta, Schulz, Holger, Albrecht, Eva, Sillanpaa, Elina, Karrasch, Stefan, Alves, Alexessander Couto, Codd, Veryan, Hovatta, Iiris, Buxton, Jessica L., Nelson, Christopher P., Broer, Linda, Hägg, Sara, Mangino, Massimo, Willemsen, Gonneke, Surakka, Ida, Ferreira, Manuel A. R., Amin, Najaf, Oostra, Ben A., Backmand, Hell M., Peltonen, Markku, Sarna, Seppo, Rantanen, Taina, Sipila, Sarianna, Korhonen, Tellervo, Madden, Pamela A. F., Gieger, Christian, Jorres, Rudolf A., Heinrich, Joachim, Behr, Juergen, Huber, Rudolf M., Peters, Annette, Strauch, Konstantin, Wichmann, H. Erich, Waldenberger, Melanie, Blakemore, Alexandra I. F., de Geus, Eco J. C., Nyholt, Dale R., Henders, Anjali K., Piirila, Paeivi L., Rissanen, Aila, Magnusson, Patrik K. E., Vinuela, Ana, Pietilainen, Kirsi H., Martin, Nicholas G., Pedersen, Nancy L., Boomsma, Dorret I., Spector, Tim D., van Duijn, Cornelia M., Kaprio, Jaakko, Samani, Nilesh J., Jarvelin, Marjo-Riitta, and Schulz, Holger
Abstract: Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
Published: 2014
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30. Genetic architecture of circulating lipid levels

Author: Demirkan, Ayse, Amin, Najaf, Isaacs, Aaron, Jarvelin, Marjo-Riitta, Whitfield, John B., Wichmann, Heinz-Erich, Kyvik, Kirsten Ohm, Rudan, Igor, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Hottenga, Jouke-Jan, Smith, Johannes J., Wild, Sarah H., Pedersen, Nancy L., Willemsen, Gonneke, Mangino, Massimo, Hayward, Caroline, Uitterlinden, Andre G., Hofman, Albert, Witteman, Jacqueline, Montgomery, Grant W., Pietilainen, Kirsi H., Rantanen, Taina, Kaprio, Jaakko, Doering, Angela, Pramstaller, Peter P., Gyllensten, Ulf, de Geus, Eco J. C., Penninx, Brenda W., Wilson, James F., Rivadeneria, Fernando, Magnusson, Patrik K. E., Boomsma, Dorret I., Spector, Tim, Campbell, Harry, Hoehne, Birgit, Martin, Nicholas G., Oostra, Ben A., McCarthy, Mark, Peltonen-Palotie, Leena, Aulchenko, Yurii, Visscher, Peter M., Ripatti, Samuli, Janssens, A. Cecile J. W., van Duijn, Cornelia M., Demirkan, Ayse, Amin, Najaf, Isaacs, Aaron, Jarvelin, Marjo-Riitta, Whitfield, John B., Wichmann, Heinz-Erich, Kyvik, Kirsten Ohm, Rudan, Igor, Gieger, Christian, Hicks, Andrew A., Johansson, Åsa, Hottenga, Jouke-Jan, Smith, Johannes J., Wild, Sarah H., Pedersen, Nancy L., Willemsen, Gonneke, Mangino, Massimo, Hayward, Caroline, Uitterlinden, Andre G., Hofman, Albert, Witteman, Jacqueline, Montgomery, Grant W., Pietilainen, Kirsi H., Rantanen, Taina, Kaprio, Jaakko, Doering, Angela, Pramstaller, Peter P., Gyllensten, Ulf, de Geus, Eco J. C., Penninx, Brenda W., Wilson, James F., Rivadeneria, Fernando, Magnusson, Patrik K. E., Boomsma, Dorret I., Spector, Tim, Campbell, Harry, Hoehne, Birgit, Martin, Nicholas G., Oostra, Ben A., McCarthy, Mark, Peltonen-Palotie, Leena, Aulchenko, Yurii, Visscher, Peter M., Ripatti, Samuli, Janssens, A. Cecile J. W., and van Duijn, Cornelia M.
Abstract: Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
Published: 2011
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31. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, Hana Lango, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I., Weedon, Michael N., Rivadeneira, Fernando, Willer, Cristen J., Jackson, Anne U., Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R., Weyant, Robert J., Segre, Ayellet V., Speliotes, Elizabeth K., Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L., Randall, Joshua C., Qi, Lu, Smith, Albert Vernon, Maegi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M., Luan, Jian'an, Thorleifsson, Gudmar, Winkler, Thomas W., Goddard, Michael E., Lo, Ken Sin, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S., Johansson, Åsa, Zillikens, M. Carola, Feitosa, Mary F., Esko, Tonu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L., Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B., Knowles, Joshua W., Kutalik, Zoltan, Monda, Keri L., Polasek, Ozren, Preuss, Michael, Rayner, Nigel W., Robertson, Neil R., Steinthorsdottir, Valgerdur, Tyrer, Jonathan P., Voight, Benjamin F., Wiklund, Fredrik, Xu, Jianfeng, Zhao, Jing Hua, Nyholt, Dale R., Pellikka, Niina, Perola, Markus, Perry, John R. B., Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L., Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I., Chen, Constance, Coin, Lachlan, Cooper, Matthew N., Dixon, Anna L., Gibson, Quince, Grundberg, Elin, Hao, Ke, Junttila, M. Juhani, Kaplan, Lee M., Kettunen, Johannes, Koenig, Inke R., Kwan, Tony, Lawrence, Robert W., Levinson, Douglas F., Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P., Mueller, Martina, Ngwa, Julius Suh, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M., Salvi, Erika, Sanna, Serena, Shi, Jianxin, Sovio, Ulla, Thompson, John R., Turchin, Michael C., Vandenput, Liesbeth, Verlaan, Dominique J., Vitart, Veronique, White, Charles C., Ziegler, Andreas, Almgren, Peter, Balmforth, Anthony J., Campbell, Harry, Citterio, Lorena, De Grandi, Alessandro, Dominiczak, Anna, Duan, Jubao, Elliott, Paul, Elosua, Roberto, Eriksson, Johan G., Freimer, Nelson B., Geus, Eco J. C., Glorioso, Nicola, Haiqing, Shen, Hartikainen, Anna-Liisa, Havulinna, Aki S., Hicks, Andrew A., Hui, Jennie, Igl, Wilmar, Illig, Thomas, Jula, Antti, Kajantie, Eero, Kilpelaeinen, Tuomas O., Koiranen, Markku, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Laitinen, Jaana, Liu, Jianjun, Lokki, Marja-Liisa, Marusic, Ana, Maschio, Andrea, Meitinger, Thomas, Mulas, Antonella, Pare, Guillaume, Parker, Alex N., Peden, John F., Petersmann, Astrid, Pichler, Irene, Pietilainen, Kirsi H., Pouta, Anneli, Riddertrale, Martin, Rotter, Jerome I., Sambrook, Jennifer G., Sanders, Alan R., Schmidt, Carsten Oliver, Sinisalo, Juha, Smit, Jan H., Stringham, Heather M., Walters, G. Bragi, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Zagato, Laura, Zgaga, Lina, Zitting, Paavo, Alavere, Helene, Farrall, Martin, McArdle, Wendy L., Nelis, Mari, Peters, Marjolein J., Ripatti, Samuli, vVan Meurs, Joyce B. J., Aben, Katja K., Ardlie, Kristin G., Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Collins, Francis S., Cusi, Daniele, den Heijer, Martin, Eiriksdottir, Gudny, Gejman, Pablo V., Hall, Alistair S., Hamsten, Anders, Huikuri, Heikki V., Iribarren, Carlos, Kahonen, Mika, Kaprio, Jaakko, Kathiresan, Sekar, Kiemeney, Lambertus, Kocher, Thomas, Launer, Lenore J., Lehtimaki, Terho, Melander, Olle, Mosley, Tom H., Jr., Musk, Arthur W., Nieminen, Markku S., O'Donnell, Christopher J., Ohlsson, Claes, Oostra, Ben, Palmer, Lyle J., Raitakari, Olli, Ridker, Paul M., Rioux, John D., Rissanen, Aila, Rivolta, Carlo, Schunkert, Heribert, Shuldiner, Alan R., Siscovick, David S., Stumvoll, Michael, Toenjes, Anke, Tuomilehto, Jaakko, van Ommen, Gert-Jan, Viikari, Jorma, Heath, Andrew C., Martin, Nicholas G., Montgomery, Grant W., Province, Michael A., Kayser, Manfred, Arnold, Alice M., Atwood, Larry D., Boerwinkle, Eric, Chanock, Stephen J., Deloukas, Panos, Gieger, Christian, Gronberg, Henrik, Hall, Per, Hattersley, Andrew T., Hengstenberg, Christian, Hoffman, Wolfgang, Lathrop, G. Mark, Salomaa, Veikko, Schreiber, Stefan, Uda, Manuela, Waterworth, Dawn, Wright, Alan F., Assimes, Themistocles L., Barroso, Ines, Hofman, Albert, Mohlke, Karen L., Boomsma, Dorret I., Caulfield, Mark J., Cupples, L. Adrienne, Erdmann, Jeanette, Fox, Caroline S., Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B., Hayes, Richard B., Jarvelin, Marjo-Ritta, Mooser, Vincent, Munroe, Patricia B., Ouwehand, Willem H., Penninx, Brenda W., Pramstaller, Peter P., Quertermous, Thomas, Rudan, Igor, Samani, Nilesh J., Spector, Timothy D., Voelzke, Henry, Watkins, Hugh, Wilson, James F., Groop, Leif C., Haritunians, Talin, Hu, Frank B., Kaplan, Robert C., Metspalu, Andres, North, Kari E., Schlessinger, David, Wareham, Nicholas J., Hunter, David J., O'Connell, Jeffrey R., Strachan, David P., Schadt, H. -Erich, Thorsteinsdottir, Unnur, Peltonen, Leena, Uitterlinden, Andre G., Visscher, Peter M., Chatterjee, Nilanjan, Loos, Ruth J. F., Boehnke, Michael, McCarthy, Mark I., Ingelsson, Erik, Lindgren, Cecilia M., Abecasis, Goncalo R., Stefansson, Kari, Frayling, Timothy M., Hirschhorn, Joel N., Allen, Hana Lango, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I., Weedon, Michael N., Rivadeneira, Fernando, Willer, Cristen J., Jackson, Anne U., Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R., Weyant, Robert J., Segre, Ayellet V., Speliotes, Elizabeth K., Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L., Randall, Joshua C., Qi, Lu, Smith, Albert Vernon, Maegi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M., Luan, Jian'an, Thorleifsson, Gudmar, Winkler, Thomas W., Goddard, Michael E., Lo, Ken Sin, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S., Johansson, Åsa, Zillikens, M. Carola, Feitosa, Mary F., Esko, Tonu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L., Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B., Knowles, Joshua W., Kutalik, Zoltan, Monda, Keri L., Polasek, Ozren, Preuss, Michael, Rayner, Nigel W., Robertson, Neil R., Steinthorsdottir, Valgerdur, Tyrer, Jonathan P., Voight, Benjamin F., Wiklund, Fredrik, Xu, Jianfeng, Zhao, Jing Hua, Nyholt, Dale R., Pellikka, Niina, Perola, Markus, Perry, John R. B., Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L., Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I., Chen, Constance, Coin, Lachlan, Cooper, Matthew N., Dixon, Anna L., Gibson, Quince, Grundberg, Elin, Hao, Ke, Junttila, M. Juhani, Kaplan, Lee M., Kettunen, Johannes, Koenig, Inke R., Kwan, Tony, Lawrence, Robert W., Levinson, Douglas F., Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P., Mueller, Martina, Ngwa, Julius Suh, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M., Salvi, Erika, Sanna, Serena, Shi, Jianxin, Sovio, Ulla, Thompson, John R., Turchin, Michael C., Vandenput, Liesbeth, Verlaan, Dominique J., Vitart, Veronique, White, Charles C., Ziegler, Andreas, Almgren, Peter, Balmforth, Anthony J., Campbell, Harry, Citterio, Lorena, De Grandi, Alessandro, Dominiczak, Anna, Duan, Jubao, Elliott, Paul, Elosua, Roberto, Eriksson, Johan G., Freimer, Nelson B., Geus, Eco J. C., Glorioso, Nicola, Haiqing, Shen, Hartikainen, Anna-Liisa, Havulinna, Aki S., Hicks, Andrew A., Hui, Jennie, Igl, Wilmar, Illig, Thomas, Jula, Antti, Kajantie, Eero, Kilpelaeinen, Tuomas O., Koiranen, Markku, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Laitinen, Jaana, Liu, Jianjun, Lokki, Marja-Liisa, Marusic, Ana, Maschio, Andrea, Meitinger, Thomas, Mulas, Antonella, Pare, Guillaume, Parker, Alex N., Peden, John F., Petersmann, Astrid, Pichler, Irene, Pietilainen, Kirsi H., Pouta, Anneli, Riddertrale, Martin, Rotter, Jerome I., Sambrook, Jennifer G., Sanders, Alan R., Schmidt, Carsten Oliver, Sinisalo, Juha, Smit, Jan H., Stringham, Heather M., Walters, G. Bragi, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Zagato, Laura, Zgaga, Lina, Zitting, Paavo, Alavere, Helene, Farrall, Martin, McArdle, Wendy L., Nelis, Mari, Peters, Marjolein J., Ripatti, Samuli, vVan Meurs, Joyce B. J., Aben, Katja K., Ardlie, Kristin G., Beckmann, Jacques S., Beilby, John P., Bergman, Richard N., Bergmann, Sven, Collins, Francis S., Cusi, Daniele, den Heijer, Martin, Eiriksdottir, Gudny, Gejman, Pablo V., Hall, Alistair S., Hamsten, Anders, Huikuri, Heikki V., Iribarren, Carlos, Kahonen, Mika, Kaprio, Jaakko, Kathiresan, Sekar, Kiemeney, Lambertus, Kocher, Thomas, Launer, Lenore J., Lehtimaki, Terho, Melander, Olle, Mosley, Tom H., Jr., Musk, Arthur W., Nieminen, Markku S., O'Donnell, Christopher J., Ohlsson, Claes, Oostra, Ben, Palmer, Lyle J., Raitakari, Olli, Ridker, Paul M., Rioux, John D., Rissanen, Aila, Rivolta, Carlo, Schunkert, Heribert, Shuldiner, Alan R., Siscovick, David S., Stumvoll, Michael, Toenjes, Anke, Tuomilehto, Jaakko, van Ommen, Gert-Jan, Viikari, Jorma, Heath, Andrew C., Martin, Nicholas G., Montgomery, Grant W., Province, Michael A., Kayser, Manfred, Arnold, Alice M., Atwood, Larry D., Boerwinkle, Eric, Chanock, Stephen J., Deloukas, Panos, Gieger, Christian, Gronberg, Henrik, Hall, Per, Hattersley, Andrew T., Hengstenberg, Christian, Hoffman, Wolfgang, Lathrop, G. Mark, Salomaa, Veikko, Schreiber, Stefan, Uda, Manuela, Waterworth, Dawn, Wright, Alan F., Assimes, Themistocles L., Barroso, Ines, Hofman, Albert, Mohlke, Karen L., Boomsma, Dorret I., Caulfield, Mark J., Cupples, L. Adrienne, Erdmann, Jeanette, Fox, Caroline S., Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B., Hayes, Richard B., Jarvelin, Marjo-Ritta, Mooser, Vincent, Munroe, Patricia B., Ouwehand, Willem H., Penninx, Brenda W., Pramstaller, Peter P., Quertermous, Thomas, Rudan, Igor, Samani, Nilesh J., Spector, Timothy D., Voelzke, Henry, Watkins, Hugh, Wilson, James F., Groop, Leif C., Haritunians, Talin, Hu, Frank B., Kaplan, Robert C., Metspalu, Andres, North, Kari E., Schlessinger, David, Wareham, Nicholas J., Hunter, David J., O'Connell, Jeffrey R., Strachan, David P., Schadt, H. -Erich, Thorsteinsdottir, Unnur, Peltonen, Leena, Uitterlinden, Andre G., Visscher, Peter M., Chatterjee, Nilanjan, Loos, Ruth J. F., Boehnke, Michael, McCarthy, Mark I., Ingelsson, Erik, Lindgren, Cecilia M., Abecasis, Goncalo R., Stefansson, Kari, Frayling, Timothy M., and Hirschhorn, Joel N.
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(1), 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(2,3). 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 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 studie, Group Author(s): Procardis Consortium
Published: 2010
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32. Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge.

Author: Bondia-Pons, Isabel, Maukonen, Johanna, Mattila, Ismo, Rissanen, Aila, Saarela, Maria, Kaprio, Jaakko, Hakkarainen, Antti, Lundbom, Jesper, Lundbom, Nina, Hyötylainen, Tuulia, Pietilainen, Kirsi H., and OrešiČ, Matej
Subjects: OBESITY, METABOLOMICS, SYSTEMS biology, BILE acids, TWIN studies
Abstract: Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m²). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels. [ABSTRACT FROM AUTHOR]
Published: 2014
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33. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

Author: Christiansen, Colette, Potier, Louis, Martin, Tiphaine C., Villicaña, Sergio, Castillo-Fernandez, Juan E., Mangino, Massimo, Menni, Cristina, Tsai, Pei-Chien, Campbell, Purdey J., Mullin, Shelby, Ordoñana, Juan R., Monteagudo, Olga, Sachdev, Perminder S., Mather, Karen A., Trollor, Julian N., Pietilainen, Kirsi H., Ollikainen, Miina, Dalgård, Christine, Kyvik, Kirsten, Christensen, Kaare, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Magnusson, Patrik K. E., Pedersen, Nancy L., Wilson, Scott G., Grundberg, Elin, Spector, Tim D., Bell, Jordana T., Christiansen, Colette, Potier, Louis, Martin, Tiphaine C., Villicaña, Sergio, Castillo-Fernandez, Juan E., Mangino, Massimo, Menni, Cristina, Tsai, Pei-Chien, Campbell, Purdey J., Mullin, Shelby, Ordoñana, Juan R., Monteagudo, Olga, Sachdev, Perminder S., Mather, Karen A., Trollor, Julian N., Pietilainen, Kirsi H., Ollikainen, Miina, Dalgård, Christine, Kyvik, Kirsten, Christensen, Kaare, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Magnusson, Patrik K. E., Pedersen, Nancy L., Wilson, Scott G., Grundberg, Elin, Spector, Tim D., and Bell, Jordana T.
Abstract: Background Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. Methods We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. Findings We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). Interpretation The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. Funding Funding acknowledgements for each cohort can be found in the Supplementary Note.

34. Greater male variability in daily energy expenditure develops through puberty.

Author: Halsey LG, Careau V, Ainslie PN, Alemán-Mateo H, Andersen LF, Anderson LJ, Arab L, Baddou I, Bandini L, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Brage S, Buchowski MS, Butte N, Camps SG, Casper R, Close GL, Colbert LH, Cooper JA, Cooper R, Dabare P, Das SK, Davies PSW, Deb S, Nyström CD, Dietz W, Dugas LR, Eaton S, Ekelund U, Hamdouchi AE, Entringer S, Forrester T, Fudge BW, Gillingham M, Goris AH, Gurven M, Haisma H, Hambly C, Hoffman D, Hoos MB, Hu S, Joonas N, Joosen A, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kriengsinyos W, Kuriyan R, Kushner RF, Lambert EV, Lanerolle P, Larsson CL, Lessan N, Löf M, Martin C, Matsiko E, Meijer GA, Morehen JC, Morton JP, Must A, Neuhouser M, Nicklas TA, Ojiambo RM, Pietilainen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich R, Racette SB, Raichen DA, Ravussin E, Redman L, Reilly JJ, Reynolds R, Roberts S, Rood JC, Samaranayake D, Sardinha LB, Scuitt AJ, Silva AM, Sinha S, Sjödin AM, Stice E, Stunkard A, Urlacher SS, Valencia ME, Valenti G, van Etten LM, Van Mil EA, Verbunt JA, Wells JCK, Wilson G, Wood B, Yoshida T, Zhang X, Murphy-Alford A, Loechl C, Luke A, Pontzer H, Rood J, Sagayama H, Westerterp KR, Wong WW, Yamada Y, and Speakman JR
Subjects: Adolescent, Young Adult, Female, Humans, Male, Adult, Reproduction, Energy Metabolism, Phenotype, Puberty, Sexual Behavior
Abstract: There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.
Published: 2023
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35. A randomized controlled trial on the effects of combined aerobic-resistance exercise on muscle strength and fatigue, glycemic control and health-related quality of life of type 2 diabetes patients.

Author: Tomas-Carus P, Ortega-Alonso A, Pietilainen KH, Santos V, Goncalves H, Ramos J, and Raimundo A
Subjects: Blood Glucose, Female, Glycated Hemoglobin, Humans, Knee Joint, Male, Mental Health, Middle Aged, Surveys and Questionnaires, Diabetes Mellitus, Type 2, Exercise physiology, Exercise Therapy, Fatigue, Muscle Strength physiology, Quality of Life
Abstract: Background: The aim of this paper was to evaluate the effects of a 12-weeks combined aerobic-resistance exercise therapy on fatigue and isokinetic muscle strength, glycemic control and health-related quality of life (HRQoL) in moderately affected type 2 diabetes (T2DM) patients., Methods: A randomized controlled trial design was employed. Forty-three T2DM patients were assigned to an exercise group (N.=22), performing 3 weekly sessions of 60 minutes of combined aerobic-resistance exercise for 12-weeks; or a no exercise control group (N.=21). Both groups were evaluated at a baseline and after 12-weeks of exercise therapy for: 1) muscle strength and fatigue by isokinetic dynamometry; 2) plasma glycated hemoglobin A1C (HbA1C); and 3) HRQoL utilizing the SF-36 questionnaire., Results: The exercise therapy led to improvements in muscle fatigue in knee extensors (-55%) and increased muscle strength in knee flexors and extensors (+15 to +30%), while HbA1C decreased (-18%). In addition, the exercising patients showed sizeable improvements in HRQoL: physical function (+53%), vitality (+21%) and mental health (+40%)., Conclusions: Twelve-weeks of combined aerobic-resistance exercise was highly effective to improve muscle strength and fatigue, glycemic control and several aspects of HRQoL in T2DM patients. These data encourage the use of aerobic and resistance exercise in the good clinical care of T2DM.
Published: 2016

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35 results on '"Pietilainen, Kirsi H."'

1. Decline in Isotope Dilution Space Ratio Above Age 60 Could Affect Energy Estimates Using the Doubly Labeled Water Method

2. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

3. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

4. Greater male variability in daily energy expenditure develops through puberty

5. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

6. Twin Study of Heritability of Eating Bread in Danish and Finnish Men and Women

7. Improving the Accuracy of Self-reports on Diet and Physical Exercise: The Co-twin Control Method

8. Effects of 32-Year Leisure Time Physical Activity Discordance in Twin Pairs on Health (TWINACTIVE Study): Aims, Design and Results for Physical Fitness

9. Growth Patterns in Young Adult Monozygotic Twin Pairs Discordant and Concordant for Obesity

10. Sex Differences in Heritability of BMI: A Comparative Study of Results from Twin Studies in Eight Countries

11. Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity

12. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity

13. Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial

14. Molecular pathways behind acquired obesity : Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI

15. GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance

16. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation

17. Modification effects of physical activity and protein intake on heritability of body size and composition

18. Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity-A Study on Rare BMI-Discordant Monozygotic Twin Pairs

19. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change

20. Genes and Environment in the Tracking of Body Size from Birth to Late Adolescence

21. Adipose tissue NAD(+)-homeostasis, sirtuins and poly(ADP-ribose) polymerases - important players in mitochondrial metabolism and metabolic health

22. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans

23. Associations Between Birth Size and Later Height From Infancy Through Adulthood: an Individual Based Pooled Analysis of 28 Twin Cohorts Participating in the Codatwins Project

24. Genetic and environmental factors affecting birth size variation:a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts

25. Birth size and gestational age in opposite-sex twins as compared to same-sex twins:An individual-based pooled analysis of 21 cohorts

26. Does The Sex Of One'S Co-Twin Affect Height And Bmi In Adulthood? A Study Of Dizygotic Adult Twins From 31 Cohorts

27. Genetic regulation of growth from birth to 18 years of age: the Swedish young male twins study

28. Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity : a study of young healthy MZ twins

29. Telomere length in circulating leukocytes is associated with lung function and disease

30. Genetic architecture of circulating lipid levels

31. Hundreds of variants clustered in genomic loci and biological pathways affect human height

32. Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge.

33. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

34. Greater male variability in daily energy expenditure develops through puberty.

35. A randomized controlled trial on the effects of combined aerobic-resistance exercise on muscle strength and fatigue, glycemic control and health-related quality of life of type 2 diabetes patients.

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