We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

The plant metabolome is characterized by extensive diversity and is often regarded as a bridge between genome and phenome. Here we report metabolic and phenotypic genome-wide studies (mGWAS and pGWAS) in rice grain that, in addition to previous metabolic GWAS in rice leaf and maize kernel, show both distinct and overlapping aspects of genetic control of metabolism within and between species. We identify new candidate genes potentially influencing important metabolic and/or morphological traits. We show that the differential genetic architecture of rice metabolism between different tissues is in part determined by tissue specific expression. Using parallel mGWAS and pGWAS we identify new candidate genes potentially responsible for variation in traits such as grain colour and size, and provide evidence of metabotype-phenotype linkage. Our study demonstrates a powerful strategy for interactive functional genomics and metabolomics in plants, especially the cloning of minor QTLs for complex phenotypic traits.

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Phenolamides (PAs) are specialized (secondary) metabolites mainly synthesized by BAHD N-acyltransferases. Here, we report metabolic profiling coupled with association and linkage mapping of 11 PAs in rice (Oryza sativa). We identified 22 loci affecting PAs in leaves and 16 loci affecting PAs in seeds. We identified eight BAHD N-acyltransferases located on five chromosomes with diverse specificities, including four aromatic amine N-acyltransferases. We show that genetic variation in PAs is determined, at least in part, by allelic variation in the tissue specificity of expression of the BAHD genes responsible for their biosynthesis. Tryptamine hydroxycinnamoyl transferase 1/2 (Os-THT1/2) and tryptamine benzoyl transferase 1/2 (Os-TBT1/2) were found to be bifunctional tryptamine/tyramine N-acyltransferases. The specificity of Os-THT1 and Os-TBT1 for agmatine involved four tandem arginine residues, which have not been identified as specificity determinants for other plant BAHD transferases, illustrating the versatility of plant BAHD transferases in acquiring new acyl acceptor specificities. With phylogenetic analysis, we identified both divergent and convergent evolution of N-acyltransferases in plants, and we suggest that the BAHD family of tryptamine/tyramine N-acyltransferases evolved conservatively in monocots, especially in Gramineae. Our work demonstrates that omics-assisted gene-to-metabolite analysis provides a useful tool for bulk gene identification and crop genetic improvement.

Although considerable progress has been made in identifying the genes regulating accumulation of hormones that are involved in leaf senescence, only a few studies have focused on natural variations in jasmonates content and much less on the underlying genetic basis. Moreover, the epigenetic regulation of jasmonate-mediated leaf senescence remains largely unknown. In this study, we carried out metabolic profiling of a worldwide collection of rice accessions and demonstrated that there are substantial variations in jasmonate levels among these accessions. A subsequent metabolite-based genome-wide association study identified candidates for two major quantitative genes (QTGs), OsPME1 and OsTSD2, affecting the content of jasmonates. Further investigations using a series of relevant mutants and transgenic lines revealed the MeOH-jasmonate cascade plays an important role in regulating leaf senescence. Moreover, we showed that OsSRT1, one of the two Sir2 (silent information regulator 2) homologs in rice, negatively regulates leaf senescence by repressing expression of the biosynthetic genes of this metabolic cascade and at least particially through histone H3K9 deacetylation of OsPME1. Taken together, our results indicate that the MeOH-jasmonates cascade and its epigenetic regulation are crucial for controlling leaf senescence process in rice.