East Asians
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2021 ◽  
Author(s):  
Akira Takagi ◽  
Masanori Matsui

COVID-19 vaccines are currently being administrated worldwide and playing a critical role in controlling the pandemic. They have been designed to elicit neutralizing antibodies against Spike protein of the original SARS-CoV-2, and hence they are less effective against SARS-CoV-2 variants with mutated Spike than the original virus. It is possible that novel variants with abilities of enhanced transmissibility and/or immunoevasion will appear in the near future and perfectly escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8+ cytotoxic T lymphocytes (CTLs). Several lines of evidence suggest the contribution of CTLs on the viral control in COVID-19, and CTLs target a wide range of proteins involving comparatively conserved non-structural proteins. Here, we identified twenty-two HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a (pp1a) of SARS-CoV-2 using computational algorithms, HLA-A*24:02 transgenic mice and the peptide-encapsulated liposomes. We focused on pp1a and HLA-A*24:02 because pp1a is relatively conserved and HLA-A*24:02 is predominant in East Asians such as Japanese. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by a number of mutations in the Sequence Read Archive database of SARS-CoV-2 variants. The information of such conserved epitopes might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any SARS-CoV-2 variants by the induction of both anti-Spike neutralizing antibodies and CTLs specific for conserved epitopes.


2021 ◽  
Author(s):  
Hang Zhou ◽  
Rasmon Kalayasiri ◽  
Yan Sun ◽  
Yaira Z Nunez ◽  
Hong-Wen Deng ◽  
...  

BACKGROUND: Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ~30 AUD risk genes in European populations, but many fewer in East Asians. METHODS: We conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from four cohorts: 1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP) sample; 2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese-GSA (array) cohort; 3) AD in a Han Chinese-Cyto (array) cohort; and 4) two AD datasets in a Thai cohort. The MVP and Thai samples included newly genotyped subjects from ongoing recruitment. In total, 2,254 cases and 11,297 controls were analyzed. An AUD polygenic risk score was analyzed in an independent sample with 4,464 East Asians (Kaiser Permanente data from dbGaP). Phenotypes from survey data and ICD-9-CM diagnoses were tested for association with the AUD PRS. RESULTS: Two risk loci were detected: the well-known functional variant rs1229984 in ADH1B and rs3782886 in BRAP (near the ALDH2 gene locus) are the lead variants. AUD PRS was significantly associated with days per week of alcohol consumption (beta = 0.43, se = 0.067, p = 2.47x10-10) and nominally associated with pack years of smoking (beta = 0.09, se = 0.05, p = 4.52x10-2) and ever vs. never smoking (beta = 0.06, se = 0.02, p = 1.14x10-2). CONCLUSIONS: This is the largest GWAS of AUD in East Asians to date. Building on previous findings, we were able to analyze pleiotropy, but did not identify any new risk regions, underscoring the importance of recruiting additional East Asian subjects for alcohol GWAS.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4715
Author(s):  
Josephine Mun Yee Ko ◽  
Shiu Yeung Lam ◽  
Lvwen Ning ◽  
Annie Wai Yeeng Chai ◽  
Lisa Chan Lei ◽  
...  

Unbiased whole-exome sequencing approaches in familial esophageal squamous cell carcinoma (ESCC) initially prioritized RAD50 as a candidate cancer predisposition gene. The combined study with 3289 Henan individuals from Northern China identified two pathogenic RAD50 protein truncation variants, p.Q672X and a recurrent p.K722fs variant at the zinc hook domain significantly conferring increased familial ESCC risk. Effects of ~10-fold higher familial ESCC risk were observed, when compared to East Asians from the gnomAD database. Functional characterization suggested that the RAD50Q672X mutation contributes a dominant-negative effect in DNA repair of double-stranded breaks. Overexpression of the RAD50Q672X and RAD50L1264F missense mutation also sensitized cell death upon replication stress stimuli induced by formaldehyde treatment and the CHK1 inhibitor, AZD7762. Our study suggested the novel insight of the potential for synthetic lethal therapeutic options for RAD50Q672X and the East-Asian-specific RAD50L1264F variants and CHK1 inhibitors. Our study also suggested the association of RAD50 LOF variants in the zinc hook domain with a higher risk of familial ESCC in Chinese.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyun Bin ◽  
Rui Wang ◽  
Youyi Huang ◽  
Rongyao Wei ◽  
Kongyang Zhu ◽  
...  

Sui people, which belong to the Tai-Kadai-speaking family, remain poorly characterized due to a lack of genome-wide data. To infer the fine-scale population genetic structure and putative genetic sources of the Sui people, we genotyped 498,655 genome-wide single-nucleotide polymorphisms (SNPs) using SNP arrays in 68 Sui individuals from seven indigenous populations in Guizhou province and Guangxi Zhuang Autonomous Region in Southwest China and co-analyzed with available East Asians via a series of population genetic methods including principal component analysis (PCA), ADMIXTURE, pairwise Fst genetic distance, f-statistics, qpWave, and qpAdm. Our results revealed that Guangxi and Guizhou Sui people showed a strong genetic affinity with populations from southern China and Southeast Asia, especially Tai-Kadai- and Hmong-Mien-speaking populations as well as ancient Iron Age Taiwan Hanben, Gongguan individuals supporting the hypothesis that Sui people came from southern China originally. The indigenous Tai-Kadai-related ancestry (represented by Li), Northern East Asian-related ancestry, and Hmong-Mien-related lineage contributed to the formation processes of the Sui people. We identified the genetic substructure within Sui groups: Guizhou Sui people were relatively homogeneous and possessed similar genetic profiles with neighboring Tai-Kadai-related populations, such as Maonan. While Sui people in Yizhou and Huanjiang of Guangxi might receive unique, additional gene flow from Hmong-Mien-speaking populations and Northern East Asians, respectively, after the divergence within other Sui populations. Sui people could be modeled as the admixture of ancient Yellow River Basin farmer-related ancestry (36.2–54.7%) and ancient coastal Southeast Asian-related ancestry (45.3–63.8%). We also identified the potential positive selection signals related to the disease susceptibility in Sui people via integrated haplotype score (iHS) and number of segregating sites by length (nSL) scores. These genomic findings provided new insights into the demographic history of Tai-Kadai-speaking Sui people and their interaction with neighboring populations in Southern China.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Moisès Coll Macià ◽  
Laurits Skov ◽  
Benjamin Marco Peter ◽  
Mikkel Heide Schierup

AbstractAfter the main Out-of-Africa event, humans interbred with Neanderthals leaving 1–2% of Neanderthal DNA scattered in small fragments in all non-African genomes today. Here we investigate what can be learned about human demographic processes from the size distribution of these fragments. We observe differences in fragment length across Eurasia with 12% longer fragments in East Asians than West Eurasians. Comparisons between extant populations with ancient samples show that these differences are caused by different rates of decay in length by recombination since the Neanderthal admixture. In concordance, we observe a strong correlation between the average fragment length and the mutation accumulation, similar to what is expected by changing the ages at reproduction as estimated from trio studies. Altogether, our results suggest differences in the generation interval across Eurasia, by up 10–20%, over the past 40,000 years. We use sex-specific mutation signatures to infer whether these changes were driven by shifts in either male or female age at reproduction, or both. We also find that previously reported variation in the mutational spectrum may be largely explained by changes to the generation interval. We conclude that Neanderthal fragment lengths provide unique insight into differences among human populations over recent history.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guanglin He ◽  
Mengge Wang ◽  
Xing Zou ◽  
Pengyu Chen ◽  
Zheng Wang ◽  
...  

Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 thousand years ago (kya) via the archaic Xiahe people and 30∼40 kya via the Nwya Devu anatomically modern human. However, the history of the Tibetan populations and their migration inferred from the ancient and modern DNA remains unclear. Here, we performed the first ancient and modern genomic meta-analysis among 3,017 Paleolithic to present-day Eastern Eurasian genomes (2,444 modern individuals from 183 populations and 573 ancient individuals). We identified a close genetic connection between the ancient-modern highland Tibetans and lowland island/coastal Neolithic Northern East Asians (NEA). This observed genetic affinity reflected the primary ancestry of high-altitude Tibeto-Burman speakers originated from the Neolithic farming populations in the Yellow River Basin. The identified pattern was consistent with the proposed common north-China origin hypothesis of the Sino-Tibetan languages and dispersal patterns of the northern millet farmers. We also observed the genetic differentiation between the highlanders and lowland NEAs. The former harbored more deeply diverged Hoabinhian/Onge-related ancestry and the latter possessed more Neolithic southern East Asian (SEA) or Siberian-related ancestry. Our reconstructed qpAdm and qpGraph models suggested the co-existence of Paleolithic and Neolithic ancestries in the Neolithic to modern East Asian highlanders. Additionally, we found that Tibetans from Ü-Tsang/Ando/Kham regions showed a strong population stratification consistent with their cultural background and geographic terrain. Ü-Tsang Tibetans possessed a stronger Chokhopani-affinity, Ando Tibetans had more Western Eurasian related ancestry and Kham Tibetans harbored greater Neolithic southern EA ancestry. Generally, ancient and modern genomes documented multiple waves of human migrations in the TP’s past. The first layer of local hunter-gatherers mixed with incoming millet farmers and arose the Chokhopani-associated Proto-Tibetan-Burman highlanders, which further respectively mixed with additional genetic contributors from the western Eurasian Steppe, Yellow River and Yangtze River and finally gave rise to the modern Ando, Ü-Tsang and Kham Tibetans.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Songchun Yang ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Robin G. Walters ◽  
...  

Abstract Background Resting heart rate (RHR) has been associated with risks of mortality and multiple chronic diseases. Previous studies, predominantly conducted in Europeans, have reported 91 independent variants associated with RHR and its genetic correlations with several cardiometabolic traits. Studies from East Asians are lacking. Methods We performed a GWAS for RHR in 87,701 participants aged 30-79 years from China Kadoorie Biobank (CKB). A linear mixed model was used under an additive model. Replication was conducted in 37,251 Chinese participants from CKB and UK Biobank. We conducted LD score regression to quantify genetic correlations across RHR and 11 cardiometabolic traits. Results Only 50 previously reported variants were replicated in CKB (=0.025). We identified ten novel loci associated with RHR (P<5 × 10-8), of which 50 candidate genes were prioritized. RHR showed significant genetic correlations with diastolic blood pressure (rg=0.258, P=5.71 × 10−10), mean arterial pressure (rg=0.225, P=3.08 × 10−8), systolic blood pressure (rg=0.170, P=4.92 × 10−5), plasma glucose (rg=0.197, P=0.003), total cholesterol (rg=0.287, P=0.012), and high-density lipoprotein (rg=0.246, P=0.030). Conclusions We identified ten novel loci associated with RHR in a large Asian cohort. The identified genetic correlations of RHR with blood pressure, glucose, and lipids indicate previously reported association of RHR with risk of all-cause death might be mediated via its correlations with cardiometabolic traits. Key messages


2021 ◽  
Vol 118 (36) ◽  
pp. e2105125118
Author(s):  
Yao Lu ◽  
Neeraj Kaushal ◽  
Xiaoning Huang ◽  
S. Michael Gaddis

Mounting reports in the media suggest that the COVID-19 pandemic has intensified prejudice and discrimination against racial/ethnic minorities, especially Asians. Existing research has focused on discrimination against Asians and is primarily based on self-reported incidents or nonrepresentative samples. We investigate the extent to which COVID-19 has fueled prejudice and discrimination against multiple racial/ethnic minority groups in the United States by examining nationally representative survey data with an embedded vignette experiment about roommate selection (collected in August 2020; n = 5,000). We find that priming COVID-19 salience has an immediate, statistically significant impact: compared to the control group, respondents in the treatment group exhibited increased prejudice and discriminatory intent against East Asian, South Asian, and Hispanic hypothetical room-seekers. The treatment effect is more pronounced in increasing extreme negative attitudes toward the three minority groups than decreasing extreme positive attitudes toward them. This is partly due to the treatment increasing the proportion of respondents who perceive these minority groups as extremely culturally incompatible (Asians and Hispanics) and extremely irresponsible (Asians). Sociopolitical factors did not moderate the treatment effects on attitudes toward Asians, but prior social contact with Hispanics mitigated prejudices against them. These findings suggest that COVID-19–fueled prejudice and discrimination have not been limited to East Asians but are part of a broader phenomenon that has affected Asians generally and Hispanics as well.


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