Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data from GWAS with data from expression quantitative trait locus (eQTL) studies to identify genes whose expression levels are associated with a complex trait because of pleiotropy. We apply the method to five human complex traits using GWAS data on up to 339,224 individuals and eQTL data on 5,311 individuals, and we prioritize 126 genes (for example, TRAF1 and ANKRD55 for rheumatoid arthritis and SNX19 and NMRAL1 for schizophrenia), of which 25 genes are new candidates; 77 genes are not the nearest annotated gene to the top associated GWAS SNP. These genes provide important leads to design future functional studies to understand the mechanism whereby DNA variation leads to complex trait variation.

Twelve genes of the PIN family in rice were analyzed for gene and protein structures and an evolutionary relationship with reported AtPINs in Arabidopsis. Four members of PIN1 (designated as OsPIN1a-d), one gene paired with AtPIN2 (OsPIN2), three members of PIN5 (OsPIN5a-c), one gene paired with AtPIN8 (OsPIN8), and three monocot-specific PINs (OsPIN9, OsPIN10a, and b) were identified from the phylogenetic analysis. Tissue-specific expression patterns of nine PIN genes among them were investigated using RT-PCR and GUS reporter. The wide variations in the expression domain in different tissues of the PIN genes were observed. In general, PIN genes are up-regulated by exogenous auxin, while different responses of different PIN genes to other hormones were found.

http://ibi.zju.edu.cn/software/qtlnetwork.

The rice (Oryza sativa L.) genome contains at least six genes exclusively with an SPX (SYG1/PHO81/XPR1) domain at the N-terminal, designated as OsSPX1-6. Here we report the diverse expression patterns of the OsSPX genes in different tissues and their responses to Pi-starvation. Among them, five genes, OsSPX1, 2, 3, 5 and 6 are responsive to Pi-starvation in shoots and/or in roots. The subcellular localization analysis indicates that OsSPX1 and OsSPX2 is exclusively located in nucleus, OsSPX3 in the cytoplasm, and OsSPX4 is a membrane localization protein. OsSPX1 regulates OsSPX2, 3 and 5 at the transcription level and is positively involved in the responses of the genes to Pi-starvation. Overexpression of OsSPX3 downregulates OsSPX5 in shoots under Pi-sufficiency. OsSPX3 negatively regulates the PSI (Pi-starvation induced) gene, OsIPS1 and is involved in the responses of miR399 and OsPHO2 to Pi-starvation. Our results suggest that OsSPX1 may be a regulator involved in the transcriptions of OsSPX2, 3 and 5. OsSPX3 plays a role in OsIPS1/miR399 mediated long distance regulation on OsPHO2. Our results also indicate that OsSPX3 is involved in plant tolerance to Pi-starvation stress.

The importance of SPX-domain-containing proteins to phosphate (Pi) homeostasis and signalling transduction has been established in plants. In this study, phylogenetic analysis revealed that OsSPX3 and OsSPX5 (SPX3/5) are paralogous SPX genes (SYG1/Pho81/XPR1) in cereal crops. SPX3/5 are specifically responsive to Pi starvation at both the transcriptional and post-transcriptional levels. Similar tissue expression patterns of the two genes and proteins were identified by in situ hybridization and the transgenic plants harbouring SPX3pro-SPX3-GUS or SPX5pro-SPX5-GUS fusions, respectively. Both SPX3/5 are localized in the nucleus and cytoplasm in rice protoplasts and plants. SPX3/5 negatively regulate root-to-shoot Pi translocation with redundant function. The data showed that the Pi-starvation-accumulated SPX3/5 proteins are players in restoring phosphate balance following phosphate starvation. In vitro and in vivo protein–protein interaction analyses indicated that these two proteins can form homodimers and heterodimers, also implying their functional redundancy. Genetic interaction analysis indicated that SPX3/5 are functional repressors of OsPHR2 (PHR2), the rice orthologue of the central regulator AtPHR1 for Pi homeostasis and Pi signalling. These results suggest that the evolution of the additional redundant paralogous SPX genes is beneficial to plants recovering Pi homeostasis after Pi starvation by PHR2 pathway.