Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC); Lagou, Vasiliki; Mägi, Reedik; Hottenga, Jouke Jan; Grallert, Harald; Perry, John R.B.; Bouatia-Naji, Nabila; Marullo, Letizia; Rybin, Denis; Jansen, Rick; Min, Josine L.; Dimas, Antigone S.; Ulrich, Anna; Zudina, Liudmila; Gådin, Jesper R.; Jiang, Longda; Faggian, Alessia; Bonnefond, Amélie; Fadista, Joao; Stathopoulou, Maria G.; Isaacs, Aaron; Willems, Sara M.; Navarro, Pau; Tanaka, Toshiko; Jackson, Anne U.; Montasser, May E.; O’Connell, Jeff R.; Bielak, Lawrence F.; Webster, Rebecca J.; Saxena, Richa; Stafford, Jeanette M.; Pourcain, Beate St; Timpson, Nicholas J.; Salo, Perttu; Shin, So Youn; Amin, Najaf; Smith, Albert V.; Li, Guo; Verweij, Niek; Goel, Anuj; Ford, Ian; Johnson, Paul C.D.; Johnson, Toby; Kapur, Karen; Thorleifsson, Gudmar; Strawbridge, Rona J.; Rasmussen-Torvik, Laura J.; Esko, Tõnu; Kovacs, Peter; Kuusisto, Johanna; Saaristo, Timo E. (2021)
Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)
Lagou, Vasiliki
Mägi, Reedik
Hottenga, Jouke Jan
Grallert, Harald
Perry, John R.B.
Bouatia-Naji, Nabila
Marullo, Letizia
Rybin, Denis
Jansen, Rick
Min, Josine L.
Dimas, Antigone S.
Ulrich, Anna
Zudina, Liudmila
Gådin, Jesper R.
Jiang, Longda
Faggian, Alessia
Bonnefond, Amélie
Fadista, Joao
Stathopoulou, Maria G.
Isaacs, Aaron
Willems, Sara M.
Navarro, Pau
Tanaka, Toshiko
Jackson, Anne U.
Montasser, May E.
O’Connell, Jeff R.
Bielak, Lawrence F.
Webster, Rebecca J.
Saxena, Richa
Stafford, Jeanette M.
Pourcain, Beate St
Timpson, Nicholas J.
Salo, Perttu
Shin, So Youn
Amin, Najaf
Smith, Albert V.
Li, Guo
Verweij, Niek
Goel, Anuj
Ford, Ian
Johnson, Paul C.D.
Johnson, Toby
Kapur, Karen
Thorleifsson, Gudmar
Strawbridge, Rona J.
Rasmussen-Torvik, Laura J.
Esko, Tõnu
Kovacs, Peter
Kuusisto, Johanna
Saaristo, Timo E.
2021
24
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202201251608
https://urn.fi/URN:NBN:fi:tuni-202201251608
Kuvaus
Peer reviewed
Tiivistelmä
Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Kokoelmat
- TUNICRIS-julkaisut [16740]