Inflation in a modified radiative seesaw model

The existence of the inflationary era in the early Universe seems to be strongly supported by recent CMB observations. However, only a few realistic inflation scenarios which have close relation to particle physics seem to have been known unfortunately. The radiative neutrino mass model with inert doublet dark matter is a promising model for the present experimental issues which cannot be explained within the standard model. In order to make the model include inflation, we extend it by a complex scalar field with a specific potential. This scalar could be closely related to the neutrino mass generation at a TeV scale as well as inflation. We show that the inflation favored by the CMB observations could be realized even if inflaton takes sub-Planck values during inflation.Comment: 20 pages, 3 figure

Inflation in a modified radiative seesaw model

金沢大学理工研究域数物科学系The existence of the inflationary era in the early Universe seems to be strongly supported by recent CMB observations. However, only a few realistic inflation scenarios which have close relation to particle physics seem to have been known unfortunately. The radiative neutrino mass model with inert doublet dark matter is a promising model for the present experimental issues which cannot be explained within the standard model. In order to make the model include inflation, we extend it by a complex scalar field with a specific potential. This scalar could be closely related to the neutrino mass generation at a TeV scale as well as inflation. We show that the inflation favored by the CMB observations could be realized even if inflaton takes sub-Planck values during inflation. © 2014 American Physical Society

Inflation due to a nonminimal coupling of singlet scalars in the radiative seesaw model

金沢大学理工研究域数物科学系The radiative neutrino mass model with inert doublet dark matter is a promising model for the present experimental issues which cannot be explained within the standard model. We study an extension of this model focusing on cosmological features brought about from the scalar sector. Inflation due to singlet scalars with hierarchical nonminimal couplings with the Ricci scalar may give a favorable solution for both neutrino masses and baryon number asymmetry in the Universe. © 2016 American Physical Society

A Systems Genetics Approach Provides a Bridge from Discovered Genetic Variants to Biological Pathways in Rheumatoid Arthritis

Genome-wide association studies (GWAS) have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA). Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC) for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR) algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: “leukocyte activation and differentiation”, “pattern-recognition receptor signaling pathway”, and “chemokines and their receptors”

GWAS of bipolar disorder

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best=1.9 × 10−9), TRANK1 (P best=2.1 × 10−9) and ODZ4 (P best=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ratio 01 (P = 1.36 x 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ratio 01 (P = 5.22 x 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ratio 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 x 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.published_or_final_versio