Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide1, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified 2, despite analysis of more than 9,000 cases3. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

Input of labile carbon may accelerate the decomposition of existing soil organic matter (priming effect), with the priming intensity depending on changes in soil nitrogen availability after permafrost thaw. However, experimental evidence for the linkage between the priming effect and post-thaw nitrogen availability is unavailable. Here we test the hypothesis that elevated nitrogen availability after permafrost collapse inhibits the priming effect by increasing microbial metabolic efficiency based on a combination of thermokarst-induced natural nitrogen gradient and nitrogen addition experiment. We find a negative correlation between the priming intensity and soil total dissolved nitrogen concentration along the thaw sequence. The negative effect is confirmed by the reduced priming effect after nitrogen addition. In contrast to the prevailing view, this nitrogen-regulated priming intensity is independent of extracellular enzyme activities but associated with microbial metabolic efficiency. These findings demonstrate that post-thaw nitrogen availability regulates topsoil carbon dynamics through its modification of microbial metabolic efficiency.

Temperature sensitivity (Q10) of soil organic matter (SOM) decomposition is a crucial parameter for predicting the fate of soil carbon (C) under global warming. However, our understanding of its regulatory mechanisms remains inadequate, which constrains its accurate parameterization in Earth system models and induces large uncertainties in predicting terrestrial C-climate feedback. Here, we conducted a long-term laboratory incubation combined with a two-pool model and manipulative experiments to examine potential mechanisms underlying the depth-associated Q10 variations in active and slow soil C pools. We found that lower microbial abundance and stronger aggregate protection were coexisting mechanisms underlying the lower Q10 in the subsoil. Of them, microbial communities were the main determinant of Q10 in the active pool, whereas aggregate protection exerted more important control in the slow pool. These results highlight the crucial role of soil C stabilization mechanisms in regulating temperature response of SOM decomposition, potentially attenuating the terrestrial C-climate feedback.