We extended our previous GWAS for psoriasis with a a multistage replication study including 8,312 cases and 12,919 controls from China as well as 3,293 cases, 4,188 controls from Germany and the USA, and 254 nuclear families from the USA. We identified 6 new susceptibility loci associated to psoriasis in Chinese, containing candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8, ZNF816A (PCombined<5×10−8) and replicated one locus 5q33.1 (TNIP1/ANXA6) previously reported (PCombined=3.8×10−21) in European studies. Two of these loci showed evidence for association evidence in the German study, at ZNF816A and GJB2 with P=3.6×10−3 and P=7.9×10−3, respectively. ERAP1 and ZNF816A were preferentially associated with Type I (early onset) psoriasis in Chinese Han population (test for heterogeneity P=6.5×10−3 and P=1.5×10−3, respectively). Comparisons with previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

Sucrose synthase catalyzes the reaction sucrose + UDP → UDP-glucose + fructose, the first step in the conversion of sucrose to starch in endosperm. Previous studies identified two tissue-specific, yet functionally redundant, sucrose synthase (SUS) genes, Sus1 and Sus2. In the present study, the wheat Sus2 orthologous gene (TaSus2) series was isolated and mapped on chromosomes 2A, 2B, and 2D. Based on sequencing in 61 wheat accessions, three single-nucleotide polymorphisms (SNPs) were detected in TaSus2-2B. These formed two haplotypes (Hap-H and Hap-L), but no diversity was found in either TaSus2-2A or TaSus2-2D. Based on the sequences of the two haplotypes, we developed a co-dominant marker, TaSus2-2B ( tgw ), which amplified 423 or 381-bp fragments in different wheat accessions. TaSus2-2B ( tgw ) was located between markers Xbarc102.2 and Xbarc91 on chromosome 2BS in a RIL population from Xiaoyan 54 × Jing 411. Association analysis suggested that the two haplotypes were significantly associated with 1,000 grain weight (TGW) in 89 modern wheat varieties in the Chinese mini-core collection. Mean TGW difference between the two haplotypes over three cropping seasons was 4.26 g (varying from 3.71 to 4.94 g). Comparative genomics analysis detected major kernel weight QTLs not only in the chromosome region containing TaSus2-2B (tgw), but also in the collinear regions of TaSus2 on rice chromosome 7 and maize chromosome 9. The preferred Hap-H haplotype for high TGW underwent very strong positive selection in Chinese wheat breeding, but not in Europe. The geographic distribution of Hap-H was perhaps determined by both latitude and the intensity of selection in wheat breeding.

No abstract

Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.