| Title: |
SMIM1 absence is associated with reduced energy expenditure and excess weight |
| Authors: |
Stefanucci, Luca; Moslemi, Camous; Tomé, Ana R.; Virtue, Samuel; Bidault, Guillaume; Gleadall, Nicholas S.; Watson, Laura P.E.; Kwa, Jing E.; Burden, Frances; Farrow, Samantha; Banasik, Karina; Bay, Jakob; Boldsen, Jens Kjærgaard; Brodersen, Thorsten; Brunak, Søren; Burgdorf, Kristoffer; Chalmer, Mona Ameri; Didriksen, Maria; Dinh, Khoa Manh; Dowsett, Joseph; Erikstrup, Christian; Feenstra, Bjarke; Geller, Frank; Gudbjartsson, Daniel; Hansen, Thomas Folkmann; Hindhede, Lotte; Hjalgrim, Henrik; Jacobsen, Rikke Louise; Jemec, Gregor; Jensen, Bitten Aagaard; Kaspersen, Katrine; Kjerulff, Bertram Dalskov; Kogelman, Lisette; Hørup Larsen, Margit Anita; Louloudis, Ioannis; Lundgaard, Agnete; Susan; Mikkelsen, Christina; Nissen, Ioanna; Nyegaard, Mette; Ostrowski, Sisse Rye; Pedersen, Ole B.; Henriksen, Alexander Pil; Rohde, Palle Duun; Rostgaard, Klaus; Schwinn, Michael; Stefansson, Kari; Stefánsson, Hreinn; Sørensen, Erik; þorsteinsdóttir, Unnur; Thørner, Lise Wegner; Bruun, Mie Topholm; Ullum, Henrik; Werge, Thomas; Westergaard, David; Chen, Ji; Spracklen, Cassandra N.; Marenne, Gaëlle; Varshney, Arushi; Corbin, Laura J.; Luan, Jian'an; Willems, Sara M.; Wu, Ying; Zhang, Xiaoshuai; Horikoshi, Momoko; Boutin, Thibaud S.; Mägi, Reedik; Waage, Johannes; Li-Gao, Ruifang; Katie Chan, Kei Hang; Yao, Jie; Anasanti, Mila D.; Chu, Audrey Y.; Claringbould, Annique; Heikkinen, Jani; Hong, Jaeyoung; Hottenga, Jouke Jan; Huo, Shaofeng; Kaakinen, Marika A.; Louie, Tin; März, Winfried; Moreno-Macias, Hortensia; Ndungu, Anne; Nelson, Sarah C.; Nolte, Ilja M.; North, Kari E.; Raulerson, Chelsea K.; Ray, Debashree; Rohde, Rebecca; Rybin, Denis; Schurmann, Claudia; Sim, Xueling; Southam, Loz; Stewart, Isobel D.; Wang, Carol A.; Wang, Yujie; Wu, Peitao; Zhang, Weihua; Ahluwalia, Tarunveer S.; Appel, Emil V.R.; Bielak, Lawrence F.; Brody, Jennifer A.; Burtt, Noël P.; Cabrera, Claudia P.; Cade, Brian E.; Chai, Jin Fang; Chai, Xiaoran; Chang, Li Ching; Chen, Chien Hsiun; Chen, Brian H.; Chitrala, Kumaraswamy Naidu; Chiu, Yen Feng; de Haan, Hugoline G.; Delgado, Graciela E.; Demirkan, Ayse; Duan, Qing; Engmann, Jorgen; Fatumo, Segun A.; Gayán, Javier; Giulianini, Franco; Gong, Jung Ho; Gustafsson, Stefan; Hai, Yang; Hartwig, Fernando P.; He, Jing; Heianza, Yoriko; Huang, Tao; Huerta-Chagoya, Alicia; Hwang, Mi Yeong; Jensen, Richard A.; Kawaguchi, Takahisa; Kentistou, Katherine A.; Kim, Young Jin; Kleber, Marcus E.; Kooner, Ishminder K.; Lai, Shuiqing; Lange, Leslie A.; Langefeld, Carl D.; Lauzon, Marie; Li, Man; Ligthart, Symen; Liu, Jun; Loh, Marie; Long, Jirong; Lyssenko, Valeriya; Mangino, Massimo; Marzi, Carola; Montasser, May E.; Nag, Abhishek; Nakatochi, Masahiro; Noce, Damia; Noordam, Raymond; Pistis, Giorgio; Preuss, Michael; Raffield, Laura; Rasmussen-Torvik, Laura J.; Rich, Stephen S.; Robertson, Neil R.; Rueedi, Rico; Ryan, Kathleen; Sanna, Serena; Saxena, Richa; Schraut, Katharina E.; Sennblad, Bengt; Setoh, Kazuya; Smith, Albert V.; Southam, Lorraine; Sparsø, Thomas; Strawbridge, Rona J.; Takeuchi, Fumihiko; Tan, Jingyi; Trompet, Stella; van den Akker, Erik; van der Most, Peter J.; Verweij, Niek; Vogel, Mandy; Wang, Heming; Wang, Chaolong; Wang, Nan; Warren, Helen R.; Wen, Wanqing; Wilsgaard, Tom; Wong, Andrew; Wood, Andrew R.; Xie, Tian; Zafarmand, Mohammad Hadi; Zhao, Jing Hua; Zhao, Wei; Amin, Najaf; Arzumanyan, Zorayr; Astrup, Arne; Bakker, Stephan J.L.; Baldassarre, Damiano; Beekman, Marian; Bergman, Richard N.; Bertoni, Alain; Blüher, Matthias; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bowden, Donald W.; Cai, Qiuyin; Campbell, Archie; Campbell, Harry; Chang, Yi Cheng; de Geus, Eco J.C.; Dehghan, Abbas; Du, Shufa; Eiriksdottir, Gudny; Farmaki, Aliki Eleni; Frånberg, Mattias; Fuchsberger, Christian; Gao, Yutang; Gjesing, Anette P.; Goel, Anuj; Han, Sohee; Hartman, Catharina A.; Herder, Christian; Hicks, Andrew A.; Hsieh, Chang Hsun; Hsueh, Willa A.; Ichihara, Sahoko; Igase, Michiya; Ikram, M. Arfan; Johnson, W. Craig; Jørgensen, Marit E.; Joshi, Peter K.; Kalyani, Rita R.; Kandeel, Fouad R.; Katsuya, Tomohiro; Khor, Chiea Chuen; Kiess, Wieland; Kolcic, Ivana; Kuulasmaa, Teemu; Kuusisto, Johanna; Läll, Kristi; Lam, Kelvin; Lawlor, Deborah A.; Lee, Nanette R.; Lemaitre, Rozenn N.; Li, Honglan; Lin, Shih Yi; Lindström, Jaana; Linneberg, Allan; Liu, Jianjun; Lorenzo, Carlos; Matsubara, Tatsuaki; Matsuda, Fumihiko; Mingrone, Geltrude; Mooijaart, Simon; Moon, Sanghoon; Nabika, Toru; Nadkarni, Girish N.; Nadler, Jerry L.; Nelis, Mari; Neville, Matt J.; Norris, Jill M.; Ohyagi, Yasumasa; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Qi, Qibin; Raven, Dennis; Reilly, Dermot F.; Reiner, Alex; Rivideneira, Fernando; Roll, Kathryn; Rudan, Igor; Sabanayagam, Charumathi; Sandow, Kevin; Sattar, Naveed; Schürmann, Annette; Shi, Jinxiu; Stringham, Heather M.; Taylor, Kent D.; Teslovich, Tanya M.; Thuesen, Betina; Timmers, Paul R.H.J.; Tremoli, Elena; Tsai, Michael Y.; Uitterlinden, Andre; van Dam, Rob M.; van Heemst, Diana; van Hylckama Vlieg, Astrid; Van Vliet-Ostaptchouk, Jana V.; Vangipurapu, Jagadish; Vestergaard, Henrik; Wang, Tao; Willems van Dijk, Ko; Zemunik, Tatijana; Abecasis, Goncalo R.; Adair, Linda S.; Aguilar-Salinas, Carlos Alberto; Alarcón-Riquelme, Marta E.; An, Ping; Aviles-Santa, Larissa; Becker, Diane M.; Beilin, Lawrence J.; Bergmann, Sven; Bisgaard, Hans; Black, Corri; Boehnke, Michael; Boerwinkle, Eric; Böhm, Bernhard O.; Bønnelykke, Klaus; Boomsma, D. I.; Bottinger, Erwin P.; Buchanan, Thomas A.; Canouil, Mickaël; Caulfield, Mark J.; Chambers, John C.; Chasman, Daniel I.; Ida Chen, Yii Der; Cheng, Ching Yu; Collins, Francis S.; Correa, Adolfo; Cucca, Francesco; Janaka de Silva, H.; Dedoussis, George; Elmståhl, Sölve; Evans, Michele K.; Ferrannini, Ele; Ferrucci, Luigi; Florez, Jose C.; Franks, Paul W.; Frayling, Timothy M.; Froguel, Philippe; Gigante, Bruna; Goodarzi, Mark O.; Gordon-Larsen, Penny; Grallert, Harald; Grarup, Niels; Grimsgaard, Sameline; Groop, Leif; Gudnason, Vilmundur; Guo, Xiuqing; Hamsten, Anders; Hansen, Torben; Hayward, Caroline; Heckbert, Susan R.; Horta, Bernardo L.; Huang, Wei; Ingelsson, Erik; James, Pankow S.; Jarvelin, Marjo Ritta; Jonas, Jost B.; Jukema, J. Wouter; Kaleebu, Pontiano; Kaplan, Robert; Kardia, Sharon L.R.; Kato, Norihiro; Keinanen-Kiukaanniemi, Sirkka M.; Kim, Bong Jo; Kivimaki, Mika; Koistinen, Heikki A.; Kooner, Jaspal S.; Körner, Antje; Kovacs, Peter; Kuh, Diana; Kumari, Meena; Kutalik, Zoltan; Laakso, Markku; Lakka, Timo A.; Launer, Lenore J.; Leander, Karin; Li, Huaixing; Lin, Xu; Lind, Lars; Lindgren, Cecilia; Liu, Simin; Loos, Ruth J.F.; Magnusson, Patrik K.E.; Mahajan, Anubha; Metspalu, Andres; Mook-Kanamori, Dennis O.; Mori, Trevor A.; Munroe, Patricia B.; Njølstad, Inger; O'Connell, Jeffrey R.; Oldehinkel, Albertine J.; Ong, Ken K.; Padmanabhan, Sandosh; Palmer, Colin N.A.; Palmer, Nicholette D.; Pedersen, Oluf; Pennell, Craig E.; Porteous, David J.; Pramstaller, Peter P.; Province, Michael A.; Psaty, Bruce M.; Qi, Lu; Raffel, Leslie J.; Rauramaa, Rainer; Redline, Susan; Ridker, Paul M.; Rosendaal, Frits R.; Saaristo, Timo E.; Sandhu, Manjinder; Saramies, Jouko; Schneiderman, Neil; Schwarz, Peter; Scott, Laura J.; Selvin, Elizabeth; Sever, Peter; Shu, Xiao Ou; Slagboom, P. Eline; Small, Kerrin S.; Smith, Blair H.; Snieder, Harold; Sofer, Tamar; Sørensen, Thorkild I.A.; Spector, Tim D.; Stanton, Alice; Steves, Claire J.; Stumvoll, Michael; Sun, Liang; Tabara, Yasuharu; Tai, E. Shyong; Timpson, Nicholas J.; Tönjes, Anke; Tuomilehto, Jaakko; Tusie, Teresa; Uusitupa, Matti; van der Harst, Pim; van Duijn, Cornelia; Vitart, Veronique; Vollenweider, Peter; Vrijkotte, Tanja G.M.; Wagenknecht, Lynne E.; Walker, Mark; Wang, Ya X.; Wareham, Nick J.; Watanabe, Richard M.; Watkins, Hugh; Wei, Wen B.; Wickremasinghe, Ananda R.; Willemsen, Gonneke; Wilson, James F.; Wong, Tien Yin; Wu, Jer Yuarn; Xiang, Anny H.; Yanek, Lisa R.; Yengo, Loïc; Yokota, Mitsuhiro; Zeggini, Eleftheria; Zheng, Wei; Zonderman, Alan B.; Rotter, Jerome I.; Gloyn, Anna L.; McCarthy, Mark I.; Dupuis, Josée; Meigs, James B.; Scott, Robert A.; Prokopenko, Inga; Leong, Aaron; Liu, Ching Ti; Parker, Stephen C.J.; Mohlke, Karen L.; Langenberg, Claudia; Wheeler, Eleanor; Morris, Andrew P.; Barroso, Inês; Võsa, Urmo; Burling, Keith; Walker, Lindsay; Ord, John; Barker, Peter; Warner, James; Frary, Amy; Renhstrom, Karola; Ashford, Sofie E.; Piper, Jo; Biggs, Gail; Erber, Wendy N.; Hoffman, Gary J.; Schoenmakers, Nadia; Rieneck, Klaus; Dziegiel, Morten H.; Azzu, Vian; Vacca, Michele; Aparicio, Hugo Javier; Hui, Qin; Cho, Kelly; Sun, Yan V.; Wilson, Peter W.; Bayraktar, Omer A.; Vidal-Puig, Antonio; Ostrowski, Sisse R.; Astle, William J.; Olsson, Martin L.; Storry, Jill R.; Ouwehand, Willem H.; Chatterjee, Krishna; Vuckovic, Dragana; Frontini, Mattia |
| Source: |
Stefanucci, L, Moslemi, C, Tomé, A R, Virtue, S, Bidault, G, Gleadall, N S, Watson, L P E, Kwa, J E, Burden, F, Farrow, S, Banasik, K, Bay, J, Boldsen, J K, Brodersen, T, Brunak, S, Burgdorf, K, Chalmer, M A, Didriksen, M, Dinh, K M, Dowsett, J, Erikstrup, C, Feenstra, B, Geller, F, Gudbjartsson, D, Hansen, T F, Hindhede, L, Hjalgrim, H, Jacobsen, R L, Jemec, G, Jensen, B A, Kaspersen, K, Kjerulff, B D, Kogelman, L, Hørup Larsen, M A, Louloudis, I, Lundgaard, A, Susan, , Mikkelsen, C, Nissen, I, Nyegaard, M, Ostrowski, S R, Pedersen, O .... |
| Publication Year: |
2024 |
| Collection: |
Aarhus University: Research |
| Subject Terms: |
blood groups; BMI; dyslipidemia; metabolism; obesity; population genetics; SMIM1; Translation to patients; Vel; weight |
| Description: |
Background: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. Methods: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1 −/− individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. Findings: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. Conclusion: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. Funding: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2666-6359; 2666-6340 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38906141; info:eu-repo/semantics/altIdentifier/pissn/2666-6359; info:eu-repo/semantics/altIdentifier/eissn/2666-6340 |
| DOI: |
10.1016/j.medj.2024.05.015 |
| Availability: |
https://pure.au.dk/portal/en/publications/3e80c713-cd25-498a-ac35-d5f0c00664f7; https://doi.org/10.1016/j.medj.2024.05.015; https://pure.au.dk/ws/files/446779362/1-s2.0-S2666634024002198-main.pdf; https://www.scopus.com/pages/publications/85198207889 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.DFB31F46 |
| Database: |
BASE |