The grazing incidence small-angle X-ray scattering (GISAXS) from structures within a thin film on a substrate is generally a superposition of the two scatterings generated by the two X-ray beams (reflected and transmitted beams) converging on the film with a difference of twice the incidence angle (α i) of the X-ray beam in their angular directions; these two scatterings may overlap or may be distinct, depending on α i. The two scatterings are further distorted by the effects of refraction. These reflection and refraction effects mean that GISAXS is complicated to analyze. To quantitatively analyze GISAXS patterns, in this study we derived a GISAXS formula under the distorted wave Born approximation. We applied this formula to the quantitative analysis of the GISAXS patterns obtained for various compositions of polystyrene-b-polyisoprene (PS-b-PI) diblock copolymer thin films on silicon substrates with native oxide layers. This analysis showed that the diblock copolymer thin films consist of hexagonally packed cylinder (HEX) structures, hexagonally perforated layer (HPL) structures, and gyroid structures, all with characteristic preferential orientations, depending on the composition of the copolymer. This is the first report of GISAXS studies of HEX, HPL, and gyroid microdomain structures in block copolymer thin films. Moreover, our study also provides a simple method for understanding GISAXS patterns and for determining the structure factor or interference function from them. Thus, the use of the GISAXS technique with our derived GISAXS formula as a data analysis engine is a very powerful tool for determining the morphologies of polymer thin films on substrates.

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,492 SLE cases and 12,675 controls from six East-Asian cohorts, to identify novel and better localize known SLE susceptibility loci. We identified 10 novel loci as well as 20 known loci with genome-wide significance. Among the novel loci, the most significant was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta=3.75×10−117, OR=2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We localized the most likely functional variants for each locus by analyzing epigenetic marks and gene regulation data. Ten putative variants are known to alter cis- or trans-gene expression. Enrichment analysis highlights the importance of these loci in B- and T-cell biology. Together with previously known loci, the explained heritability of SLE increases to 24%. Novel loci share functional and ontological characteristics with previously reported loci, and are possible drug targets for SLE therapeutics.

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Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRb1 at amino acid position 13, located outside the classical shared epitope (P omnibus 5 6.9 3 10 2135 ). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr Gly > Ser)-but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional P omnibus 5 2.2 3 10 233) and 74 (conditional P omnibus 5 1.1 3 10 28). Outside of HLA-DRb1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P 5 3.8 3 10 26) and HLA-DPb1 (Phe9, conditional P 5 3.0 3 10 25 ) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino † These authors jointly directed this project.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature1. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production2, predisposes to SLE (odds ratio (OR)=3.47 in Asians (Pmeta=3.1×10−104), OR=2.61 in European Americans, OR=2.02 in African Americans) and other autoimmune diseases, including primary Sjögren’s syndrome (OR=2.45 in Chinese, OR=2.35 in European Americans) and rheumatoid arthritis (OR=1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.