OBJECTIVE: While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited.
METHODS: To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via a multitrait genome-wide association study. Global and local genetic correlations were estimated by LDSC and ρ-HESS. Pleiotropic loci were identified by the multitrait analysis of GWAS (MTAG).
RESULTS: Besides the significant correlation between depression and SCZ, our analysis revealed genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Further multitrait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ.
CONCLUSIONS: Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.

Acral peeling skin syndrome (APSS; MIM 609796) is a rare genodermatosis characterized by painless focal cutaneous exfoliation of the dorsal hands and feet, typically displaying autosomal recessive inheritance. While cases associated with a founder mutation in TGM5 are relatively common in European Caucasian populations, no APSS cases have been reported from Japan or other East Asian countries. In contrast, Nagashima-type palmoplantar keratosis (NPPK; MIM 615598), caused by variants in SERPINB7, is relatively common in East Asia due to founder mutations. We describe a 27-year-old Japanese woman with spontaneous focal cutaneous exfoliation of the dorsal hand following prolonged glove use, indicative of APSS. Histopathological examination revealed a cleft between the stratum corneum and stratum granulosum and within the horny layer of the epidermis, supporting this diagnosis. However, her mother and maternal uncle exhibited similar symptoms, and there was no reported consanguinity in the patient\'s parents or grandparents, prompting suspicion of an autosomal dominant genodermatosis. Whole-genome sequencing (WGS) revealed compound heterozygous variants in TGM5 (c.1037G>A and c.684 + 1G>A) as suspected causative variants in the patient, leading to an APSS diagnosis, the first reported in East Asia. On the other hand, her mother and maternal uncle were diagnosed with NPPK due to compound heterozygous pathogenic variants in SERPINB7 (c.796C>T and c.455-1G>A). This case highlights the complexity of diagnosing skin disorders when multiple genodermatoses with similar phenotypes exist within a pedigree. Comprehensive genetic analyses, such as whole-exome sequencing and WGS, are invaluable for identifying causative variants in such complex cases.

Rosacea is a chronic inflammatory disorder primarily affecting the facial skin, prominently involving the cheeks, nose, chin, forehead, and periorbital area. Cutaneous manifestations encompass persistent facial erythema, phymas, papules, pustules, telangiectasia, and flushing. The pathogenesis of rosacea is associated with various exacerbating or triggering factors, including microbial infestation, temperature fluctuations, sunlight exposure, physical exertion, emotional stress, consumption of hot beverages and spicy foods, and exposure to airborne pollen. These environmental factors interact with genetic predispositions in the development of rosacea. The roles of the lipophilic microbiome, ultraviolet radiation, nociceptive responses, and vascular alterations have been proposed as significant factors in the pathogenesis. These insights contribute to understanding the anatomical specificity of facial involvement and the progressive nature of rosacea. East Asian skin, predominantly classified as Fitzpatrick skin phototypes III to IV, is characterized by relatively diminished skin barrier function and increased sensitivity to irritants. Airborne pollen exposure may particularly act as a trigger in East Asian individuals, possibly mediated through toll-like receptors. The lack of specificity in objective clinical and histopathological findings leads to diagnostic challenges for individuals with colored skin, including East Asians, particularly when erythema is the sole objective manifestation. An alternative diagnostic scheme may thus be necessary. A diagnostic approach emphasizing vascular manifestations and nociceptive symptoms potentially holds promise for individuals with darker skin tones. More research focusing on potential variations in skin physiology across different racial groups is essential to establish more effective diagnostic schemes applicable to both dark and light skin colors.

Immunoglobulins (Igs) have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations.

Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients\' prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK-STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient\'s age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331-32.677, P < 0.001; Hazard ratio = 2.547, 95% CI 1.195-5.432, P = 0.016, respectively). In summary, this study provides valuable insights into understanding sex disparity in HCC in the East Asian population. Validation through larger cohorts and extensive sequencing efforts is warranted.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

UNASSIGNED: Understanding the characteristics of alveolar bone resorption in an East Asian population after maxillary incisor extraction and providing a reference for implant treatment plans.
UNASSIGNED: Cone-beam computerized tomography (CBCT) data of 125 East Asian patients with unilateral extraction of maxillary incisors for 3 months were collected. The alveolar bone width and height in the extraction sites were measured and compared with the corresponding contralateral sites.
UNASSIGNED: The differences in alveolar bone width between the extraction site and contralateral site were as follows: 4.11 mm, 2.68 mm, and 2.09 mm (3 mm, 5 mm, 7 mm apical from CEJ of the contralateral tooth). Data are expressed as the median. The horizontal resorption ratio of alveolar bone was 49.94 %, 31.5 %, and 24.46 %. The difference in alveolar bone height was 0.78 mm. The vertical resorption ratio was 7.78 %. The resorption did not differ significantly between sexes and was not significantly affected by tooth positions.
UNASSIGNED: In the studied East Asian population, significant horizontal and vertical alveolar bone resorption occurs after natural healing of maxillary incisor extraction for 3 months. The closer to the alveolar ridge crest, the more significant the horizontal resorption, resulting in an \"inverted triangle\" shape residual alveolar bone.

This study investigated the underlying causes of the myopic outcomes of the optic-based newer formulas (Barrett Universal II, EVO 2.0, Kane, Hoffer-QST and PEARL-DGS) in long Korean eyes with Alcon TFNT intraocular lens (IOL) implantation. Postoperative data from 3100 randomly selected eyes of 3100 patients were analyzed to compare the reference back-calculated effective lens positions (ELPs) based on the Haigis formula using conventional axial length (AL) and Cooke-modified AL (CMAL) with the predicted ELP of each single- and triple-optimized Haigis formula applied to AL- and CMAL. Contrary to the AL-applied Haigis formula, the predicted ELP curve of the CMAL-applied, single-optimized Haigis formula, simulating the methods of the newer formulas, exhibited a significant upward deviation from the back-calculated ELP in long eyes. The relationship between the AL and anterior chamber depth in our long-eyed population differed from that in the base population of the PEARL-DGS formula. The myopic outcomes in long eyes appeared to stem from the substantial overestimation of the postoperative IOL position with AL modification, leading to the implantation of inappropriately higher-powered IOLs. This discrepancy may be attributed to the ethnic differences in ocular biometrics, particularly the relatively smaller anterior segment in East Asian patients with long AL.

UNASSIGNED: The COVID-19 pandemic fueled stigmatization and discrimination, particularly towards individuals of Chinese or East Asian ethnicity. We conducted interviews with members of the public in Canada in order to describe and understand stigma perceptions and experiences during the COVID-19 pandemic.
UNASSIGNED: We used a phenomenological approach to describe stigma experiences of Canadian residents during the COVID-19 pandemic and compared the stigma perceptions and experiences of East Asian and non-East Asian individuals. Participants were invited to take part in a single, semi-structured interview. The interview guide was rooted in the Health Stigma and Discrimination Framework (HSDF). Interviews were conducted in English, Mandarin, and Cantonese. Following participant consent, interviews were audio recorded and transcribed verbatim. Data were double coded and analyzed using qualitative content analysis guided by a framework approach.
UNASSIGNED: A total of 55 interviews were conducted between May and December 2020. Fifty-five percent of the sample identified as East Asian, 67.3% identified as women, and mean age was 52 years (range 20-76). Fear of infection, fear of social and economic ramifications, and blame for COVID-19 were reported drivers of stigma. Participants described preexisting perceptions on cultural norms and media influence as facilitators of stigma that propagated harmful stereotypes, particularly against Chinese and East Asian individuals. Participants observed or experienced stigmatization towards place of residence, race/ethnicity, culture, language, occupation, and age. Stigma manifestations present in the public and media had direct negative impacts on East Asian, particularly Chinese, participants, regardless of whether or not they personally experienced discrimination.
UNASSIGNED: We used the HSDF as a rooting framework to describe perceptions and impact of stigma, particularly as they related to race/ethnicity-based stigmatization in Canada. Participants reported a number of drivers and facilitators of stigma that impacted perceptions and experiences. These findings should be used to develop sustained strategies to mitigate stigma during public health emergencies or other major crises.
UNASSIGNED: The online version contains supplementary material available at 10.1186/s44263-023-00020-7.

BACKGROUND: The alcohol-induced facial flushing phenotype (flushing) is common among East Asians. Despite a small intake of alcohol, they experience heightened levels of acetaldehyde, a group-1 carcinogen, which, in turn, causes unpleasant symptoms such as redness, acting as a robust protective mechanism against consuming alcohol. However, some individuals with this genetic trait exhibit weakened alcohol restraint, which increases the risk of developing alcohol-related cancers, such as esophageal and head or neck cancer, by several times. Although this flushing phenomenon is crucial for public health, there is a paucity of studies that have comprehensively investigated the effect of flushing or its genotype on alcohol consumption in a large group of East Asians while controlling for various sociodemographic and health-related variables at a country level.
OBJECTIVE: This 2-year cross-sectional study aims to explore the effect of flushing on drinking behavior in Koreans and to examine whether the effect varies across sociodemographic and health-related factors.
METHODS: We used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for 2019 and 2020 conducted by the Korea Disease Control and Prevention Agency. Our sample comprised 10,660 Korean adults. The study investigated the association of 26 variables, including flushing, with drinking frequency and amount. The effect of flushing was examined with and without adjusting for the other 25 variables using multinomial logistic regression analysis. In addition, we tested the interaction effect with flushing and conducted a simple effect analysis. We used complex sample design elements, including strata, clusters, and weights, to obtain unbiased results for the Rao-Scott χ2 test, 2-tailed t test, and multinomial logistic regression analysis.
RESULTS: The suppressive effect of flushing was significant (P<.001) across all pronounced categories of alcohol consumption in 2019. The ranges of standardized regression slopes and odds ratios (ORs) were -6.70≥β≥-11.25 and 0.78≥OR≥0.50 for frequency and -5.37≥β≥-17.64 and 0.73≥OR≥0.36 for amount, respectively. The effect became somewhat stronger when adjusted for confounders. The effect also exhibited an overall stronger trend as the severity of alcohol consumption increased. The β values and ORs were consistently smaller in 2020 compared to the previous year. A simple effect analysis revealed a diminished alcohol-suppressive effect of flushing on alcohol consumption for specific groups (eg, those with low levels of education, limited family support, physical labor, or health-related issues).
CONCLUSIONS: Our findings suggest that flushing suppresses drinking in Koreans overall but has little or no effect in certain susceptible populations. Therefore, health authorities should conduct targeted epidemiological studies to assess drinking patterns and disease profiles, particularly regarding alcohol-related cancers, and establish effective preventive measures tailored to this population.