Article
A rare variant in GPR156 associated with depression in a Mennonite pedigree causes habenula hyperactivity and stress sensitivity in mice.
Proceedings of the National Academy of Sciences of the United States of America - 22 Apr 2025
Miller Bradley R, Gonzaga-Jauregui Claudia, Brigatti Karlla W, de Jong Job, Breese Robert S, Ko Seung Yeon, Puffenberger Erik G, Van Hout Cristopher, Young Millie, Luna Victor M, Staples Jeffrey, First Michael B, Gregoire Hilledna J, Dwork Andrew J, Pefanis Evangelos, McCarthy Shane, Brydges Susannah, Rojas Jose, Ye Bin, Stahl Eli, Di Gioia Silvio Alessandro, Hen René, Elwood Kevin, Rosoklija Gorazd, Li Dadong, Mellis Scott, Carey David, Croll Susan D, Overton John D, Macdonald Lynn E, Economides Aris N, Shuldiner Alan R, Chuhma Nao, Rayport Stephen, Amin Najaf, Kushner Steven A, Alessandri-Haber Nicole, Markx Sander, Strauss Kevin A
Abstract excerpt
Major depressive disorder (MDD) is a leading cause of disability worldwide. Risk for MDD is heritable, and the genetic structure of founder populations enables investigation of rare susceptibility alleles with large effect. In an extended Old Order Mennonite family cohort, we identified a rare missense variant in GPR156 (c.1599G>T, p.Glu533Asp) associated with a two-fold increase in the relative risk of MDD....
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