SMIM1 absence is associated with reduced energy expenditure and excess weight.
Details
Serval ID
serval:BIB_253F4C15279B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
SMIM1 absence is associated with reduced energy expenditure and excess weight.
Journal
Med
Working group(s)
DBDS Genetic Consortium, MAGIC
Contributor(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 S, Mikkelsen C., Nissen I., Nyegaard M., Ostrowski S.R., Pedersen O.B., Henriksen A.P., Rohde P.D., Rostgaard K., Schwinn M., Stefansson K., Stefánsson H., Sørensen E., Þorsteinsdóttir U., Thørner L.W., Bruun M.T., Ullum H., Werge T., Westergaard D., Chen J., Spracklen C.N., Marenne G., Varshney A., Corbin L.J., Luan J., Willems S.M., Wu Y., Zhang X., Horikoshi M., Boutin T.S., Mägi R., Waage J., Li-Gao R., Katie Chan K.H., Yao J., Anasanti M.D., Chu A.Y., Claringbould A., Heikkinen J., Hong J., Hottenga J.J., Huo S., Kaakinen M.A., Louie T., März W., Moreno-Macias H., Ndungu A., Nelson S.C., Nolte I.M., North K.E., Raulerson C.K., Ray D., Rohde R., Rybin D., Schurmann C., Sim X., Southam L., Stewart I.D., Wang C.A., Wang Y., Wu P., Zhang W., Ahluwalia T.S., Appel EVR, Bielak L.F., Brody J.A., Burtt N.P., Cabrera C.P., Cade B.E., Chai J.F., Chai X., Chang L.C., Chen C.H., Chen B.H., Chitrala K.N., Chiu Y.F., de Haan H.G., Delgado G.E., Demirkan A., Duan Q., Engmann J., Fatumo S.A., Gayán J., Giulianini F., Gong J.H., Gustafsson S., Hai Y., Hartwig F.P., He J., Heianza Y., Huang T., Huerta-Chagoya A., Hwang M.Y., Jensen R.A., Kawaguchi T., Kentistou K.A., Kim Y.J., Kleber M.E., Kooner I.K., Lai S., Lange L.A., Langefeld C.D., Lauzon M., Li M., Ligthart S., Liu J., Loh M., Long J., Lyssenko V., Mangino M., Marzi C., Montasser M.E., Nag A., Nakatochi M., Noce D., Noordam R., Pistis G., Preuss M., Raffield L., Rasmussen-Torvik L.J., Rich S.S., Robertson N.R., Rueedi R., Ryan K., Sanna S., Saxena R., Schraut K.E., Sennblad B., Setoh K., Smith A.V., Southam L., Sparsø T., Strawbridge R.J., Takeuchi F., Tan J., Trompet S., van den Akker E., van der Most P.J., Verweij N., Vogel M., Wang H., Wang C., Wang N., Warren H.R., Wen W., Wilsgaard T., Wong A., Wood A.R., Xie T., Zafarmand M.H., Zhao J.H., Zhao W., Amin N., Arzumanyan Z., Astrup A., Bakker SJL, Baldassarre D., Beekman M., Bergman R.N., Bertoni A., Blüher M., Bonnycastle L.L., Bornstein S.R., Bowden D.W., Cai Q., Campbell A., Campbell H., Chang Y.C., de Geus EJC, Dehghan A., Du S., Eiriksdottir G., Farmaki A.E., Frånberg M., Fuchsberger C., Gao Y., Gjesing A.P., Goel A., Han S., Hartman C.A., Herder C., Hicks A.A., Hsieh C.H., Hsueh W.A., Ichihara S., Igase M., Ikram M.A., Johnson W.C., Jørgensen M.E., Joshi P.K., Kalyani R.R., Kandeel F.R., Katsuya T., Khor C.C., Kiess W., Kolcic I., Kuulasmaa T., Kuusisto J., Läll K., Lam K., Lawlor D.A., Lee N.R., Lemaitre R.N., Li H., Lin S.Y., Lindström J., Linneberg A., Liu J., Lorenzo C., Matsubara T., Matsuda F., Mingrone G., Mooijaart S., Moon S., Nabika T., Nadkarni G.N., Nadler J.L., Nelis M., Neville M.J., Norris J.M., Ohyagi Y., Peters A., Peyser P.A., Polasek O., Qi Q., Raven D., Reilly D.F., Reiner A., Rivideneira F., Roll K., Rudan I., Sabanayagam C., Sandow K., Sattar N., Schürmann A., Shi J., Stringham H.M., Taylor K.D., Teslovich T.M., Thuesen B., Timmers PRHJ, Tremoli E., Tsai M.Y., Uitterlinden A., van Dam R.M., van Heemst D., van Hylckama Vlieg A., Van Vliet-Ostaptchouk J.V., Vangipurapu J., Vestergaard H., Wang T., Willems van Dijk K., Zemunik T., Abecasis G.R., Adair L.S., Aguilar-Salinas C.A., Alarcón-Riquelme M.E., An P., Aviles-Santa L., Becker D.M., Beilin L.J., Bergmann S., Bisgaard H., Black C., Boehnke M., Boerwinkle E., Böhm B.O., Bønnelykke K., Boomsma D.I., Bottinger E.P., Buchanan T.A., Canouil M., Caulfield M.J., Chambers J.C., Chasman D.I., Ida Chen Y.D., Cheng C.Y., Collins F.S., Correa A., Cucca F., Janaka de Silva H., Dedoussis G., Elmståhl S., Evans M.K., Ferrannini E., Ferrucci L., Florez J.C., Franks P.W., Frayling T.M., Froguel P., Gigante B., Goodarzi M.O., Gordon-Larsen P., Grallert H., Grarup N., Grimsgaard S., Groop L., Gudnason V., Guo X., Hamsten A., Hansen T., Hayward C., Heckbert S.R., Horta B.L., Huang W., Ingelsson E., James P.S., Jarvelin M.R., Jonas J.B., Jukema J.W., Kaleebu P., Kaplan R., Kardia SLR, Kato N., Keinanen-Kiukaanniemi S.M., Kim B.J., Kivimaki M., Koistinen H.A., Kooner J.S., Körner A., Kovacs P., Kuh D., Kumari M., Kutalik Z., Laakso M., Lakka T.A., Launer L.J., Leander K., Li H., Lin X., Lind L., Lindgren C., Liu S., Loos RJF, Magnusson PKE, Mahajan A., Metspalu A., Mook-Kanamori D.O., Mori T.A., Munroe P.B., Njølstad I., O'Connell J.R., Oldehinkel A.J., Ong K.K., Padmanabhan S., Palmer CNA, Palmer N.D., Pedersen O., Pennell C.E., Porteous D.J., Pramstaller P.P., Province M.A., Psaty B.M., Qi L., Raffel L.J., Rauramaa R., Redline S., Ridker P.M., Rosendaal F.R., Saaristo T.E., Sandhu M., Saramies J., Schneiderman N., Schwarz P., Scott L.J., Selvin E., Sever P., Shu X.O., Slagboom P.E., Small K.S., Smith B.H., Snieder H., Sofer T., Sørensen TIA, Spector T.D., Stanton A., Steves C.J., Stumvoll M., Sun L., Tabara Y., Tai E.S., Timpson N.J., Tönjes A., Tuomilehto J., Tusie T., Uusitupa M., van der Harst P., van Duijn C., Vitart V., Vollenweider P., Vrijkotte TGM, Wagenknecht L.E., Walker M., Wang Y.X., Wareham N.J., Watanabe R.M., Watkins H., Wei W.B., Wickremasinghe A.R., Willemsen G., Wilson J.F., Wong T.Y., Wu J.Y., Xiang A.H., Yanek L.R., Yengo L., Yokota M., Zeggini E., Zheng W., Zonderman A.B., Rotter J.I., Gloyn A.L., McCarthy M.I., Dupuis J., Meigs J.B., Scott R.A., Prokopenko I., Leong A., Liu C.T., Parker SCJ, Mohlke K.L., Langenberg C., Wheeler E., Morris A.P., Barroso I.
ISSN
2666-6340 (Electronic)
ISSN-L
2666-6340
Publication state
Published
Issued date
13/09/2024
Peer-reviewed
Oui
Volume
5
Number
9
Pages
1083-1095.e6
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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 <sup>-/-</sup> individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.
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.
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.
This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.
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 <sup>-/-</sup> individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.
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.
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.
This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.
Keywords
Adult, Female, Humans, Male, Middle Aged, Adiponectin/genetics, Adiponectin/metabolism, Case-Control Studies, Energy Metabolism/genetics, Leptin/blood, Leptin/genetics, Leptin/metabolism, Loss of Function Mutation, Membrane Proteins/genetics, Obesity/genetics, Obesity/metabolism, Overweight/genetics, Thyroid Hormones/blood, Thyroid Hormones/metabolism, BMI, SMIM1, Translation to patients, Vel, blood groups, dyslipidemia, metabolism, obesity, population genetics, weight
Pubmed
Web of science
Open Access
Yes
Create date
04/06/2025 16:04
Last modification date
05/06/2025 7:19
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