METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4).
RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99).
CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries.
RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence).
CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.
METHODS: Stimuli were presented in both monocular and dichoptic conditions at eight visual field locations/eye. The incommensurate stimulus frequencies ranged from 15.45 to 21.51 Hz. Five stimulus conditions differing in spatial frequency and orientation were examined for three viewing conditions. The resulting 15 stimulus conditions were examined in 16 normal subjects who repeated all conditions twice.
RESULTS: Several significant independent effects were identified. Response amplitudes were reduced for dichoptic viewing (by 0.85 times, p<4 x 10(-11)); offset by increases in responses for between eye differences of one octave of spatial frequency: lower (1.15 times, 0.1 cpd); higher (1.29 times, 0.4 cpd), both p<1.8 x 10(-7). Crossed orientations produced significant effects upon response phase (p=0.023) but not amplitude (p=0.062).
CONCLUSIONS: The results indicated that dichoptic evoked potentials using multifocal frequency-doubling illusion stimuli are practical. The use of crossed orientation, or differing spatial frequencies, in the two eyes reduced binocular interactions.
SIGNIFICANCE: The results indicate a method wherein several spatial or temporal and frequencies per visual field region can be tested in reasonable time using a multifocal VEP using spatial frequency-doubling stimuli.