Southeast Asian Ancestry Research Articles

A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes

Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries, particularly from Asia. Here, we present a WGS catalogue of 73,035 SVs from 8392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~65% (47,770 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 42,239 novel SVs that are specific to Asian populations. 52% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting major clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification of potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research.

Abstract C075: Socioeconomic status and genetic ancestry correlate with differences in clinical outcomes for colorectal cancer patients treated at a single tertiary cancer center

Abstract Intro: Lower socioeconomic status (SES) and African ancestry have been linked to poor overall survival (OS) in colorectal cancer (CRC). To better understand the interplay between these variables, we analyzed clinical and genomic real-world data from a large cohort of patients treated at a single tertiary center. Methods: Clinical annotations including sex, primary tumor location, age and stage at diagnosis were extracted from the electronic health record for 3,817 CRC patients who underwent clinical genomic sequencing at Memorial Sloan Kettering Cancer Center between 2014 and 2022. We also cataloged each patient’s type of primary health insurance (commercial, Medicare, Medicaid or self-pay). Socioeconomic status was assessed from each patient’s billing address using the Yost index (YI), which is a location-dependent percentile score based on household incomes, house values, rent, poverty, education, and employment statistics. Genetic ancestry was determined from DNA sequencing data using reference populations from the 1000 Genomes project, including European (EUR), African (AFR), East Asian (EAS), and Southeast Asian (SAS). Specific ancestries were assigned based on an ancestral fraction of >80%, otherwise patients were labeled as admixed (ADM). OS was measured from time of diagnosis to last follow-up. Results: Our cohort included 2,627 EUR, 195 EAS, 206 AFR, 61 SAS and 728 ADM patients. The median YI within our cohort was 18 [IQR: 30]. No significant associations were observed between YI and primary tumor location, age or stage at diagnosis. We observed significant differences in YI based on type of health insurance (median 15 for commercial vs. 29 for Medicaid, p<0.0001) and sex (median 15 in males vs. 17 in females, p=0.0113). YI was also strongly associated with genetic ancestry, with AFR patients exhibiting significantly higher YI values than other ancestries (median 45.5 vs. 14, p<0.0001). No significant differences in YI were observed among EUR, EAS and SAS patients. When all ancestries were analyzed together, patients within the bottom YI quartile (most affluent) had significantly longer OS than patients from the top YI quartile (most deprived) (median 52.3 vs. 61.6 months, p=0.023). No differences in OS were observed between EUR, EAS and SAS patients, but patients of AFR ancestry had significantly shorter OS than the rest (median 44.5 vs. 56.5 months, p= 0.016). When the analysis was restricted to patients of EUR, EAS and SAS ancestry, OS was still significantly shorter for patients within the top vs. bottom YI quartile (median 52.6 vs. 64.4 months, p=0.011). Conclusions: Patients of African ancestry exhibited lower socioeconomic status and shorter survival. Even when the analysis was restricted to other genetic ancestries, patients with the lowest socioeconomic status still had poorer clinical outcomes. The existence of these differences within a relatively homogeneous cohort of patients treated at the same institution highlights the need to better understand and address health disparities in CRC. Citation Format: Tejiri Agbamu, Xuechun Bai, Henry Walch, Michele Waters, Anisha Luthra, Kanika Arora, Christopher Fong, Doori Rose, Hannah Williams, Michael Berger, Karuna Ganesh, Julio Garcia-Aguilar, Nikolaus Schultz, Rona Yaegar, Walid Chatila, Francisco Sanchez-Vega. Socioeconomic status and genetic ancestry correlate with differences in clinical outcomes for colorectal cancer patients treated at a single tertiary cancer center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C075.

Origin and population structure of native dog breeds in the Korean peninsula and East Asia

To study the ancestry and phylogenetic relationships of native Korean dog breeds to other Asian dog populations, we analyzed nucleotide variations in whole-genome sequences of 205 canid individuals. Sapsaree, Northern Chinese indigenous dog, and Tibetan Mastiff were largely related to West Eurasian ancestry. Jindo, Donggyeongi, Shiba, Southern Chinese indigenous (SCHI), Vietnamese indigenous dogs (VIET), and Indonesian indigenous dogs were related to Southeast and East Asian ancestry. Among East Asian dog breeds, Sapsaree presented the highest haplotype sharing with German Shepherds, indicating ancient admixture of European ancestry to modern East Asian dog breeds. SCHI showed greater haplotype sharing with New Guinea singing dogs, VIET, and Jindo than with other Asian breeds. The predicted divergence time of East Asian populations from their common ancestor was approximately 2,000 to 11,000 years ago. Our results expand understanding of the genetic history of dogs in the Korean peninsula to the Asian continent and Oceanic region.

Characteristics of Multiple Sclerosis and Demyelinating Disease in an Asian American Population (P9-3.009)

<h3>Objective:</h3> To explore the clinical presentation of MS and neuromyelitis optica spectrum disorder (NMOSD) in patients of Asian ancestry in the United States. <h3>Background:</h3> Race and ancestry influence the course of demyelinating conditions like Multiple Sclerosis (MS). Asian patients are underrepresented in clinical research in the United States. <h3>Design/Methods:</h3> Demographic, clinical and radiologic data were extracted from the medical record for adults with Asian self-identified race and diagnosis of demyelinating disease cared for at a single North American MS center between 2006/02/06 and 2022/06/09. Descriptive statistics were used to describe the cohort, then demographic and clinical factors were compared according to region of ancestry. <h3>Results:</h3> The cohort included 282 patients from 11 different countries; 73.1% were born in Asia. Most patients (94.7%) preferred English for medical communication, but fewer of East Asian ancestry did (p=0.0001). South Asian ancestry was associated with higher neighborhood household income (p=0.002) and Southeast Asian ancestry with smoking (p=0.08). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were of East Asian and Southeast Asian ancestry (p=0.004). For MS patients, levels of optic nerve and spinal cord involvement were similar across regions of ancestry. Most (83.7%) patients were currently on MS treatment (42.3% on antiCD20 therapies). MS Severity Scale (MSSS), while similar to the clinic average. was worse with Southeast Asian ancestry (p=0.006) and also worse with smoking, and lower neighborhood median household income or educational attainment. <h3>Conclusions:</h3> Patients of Asian ancestry are underrepresented in research in the United States. In this cohort, Asian patients with MS were actively treated and disease severity reflected the overall clinic. Both region of origin and neighborhood socioeconomic factors were associated with disease characteristics. Further research is needed to uncover genetic, socioeconomic, or environmental factors accounting for worse MSSS in Southeast Asian patients. <b>Disclosure:</b> Dr. Fan has nothing to disclose. Ms. Alexander has nothing to disclose. Mr. Poole has nothing to disclose. Ms. Wijangco has received research support from National Institutes of Health. Dr. Henson has received personal compensation for serving as an employee of Piedmont Healthcare. An immediate family member of Dr. Henson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tempus. Dr. Henson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various law firms. Ruth Dobson has nothing to disclose. Dr. Guo has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis.

Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.

Multiancestral polygenic risk score for pediatric asthma

Asthma is the most common chronic condition in children and the third leading cause of hospitalization in pediatrics. The genome-wide association study catalog reports 140 studies with genome-wide significance. Apolygenic risk score (PRS) with predictive value across ancestries has not been evaluated for this important trait. This study aimed to train and validate a PRS relying on genetic determinants for asthma to provide predictions for disease occurrence in pediatric cohorts of diverse ancestries. This study applied a Bayesian regression framework method using the Trans-National Asthma Genetic Consortium genome-wide association study summary statistics to derive a multiancestral PRS score, used one Electronic Medical Records and Genomics (eMERGE) cohort as a training set, used a second independent eMERGE cohort to validate the score, and used the UK Biobank data to replicate the findings. Aphenome-wide association study was performed using the PRS to identify shared genetic etiology with other phenotypes. The multiancestral asthma PRS was associated with asthma in the 2 pediatric validation datasets. Overall, the multiancestral asthma PRS has an area under the curve (AUC) of 0.70 (95% CI, 0.69-0.72) in the pediatric validation 1 and AUC of 0.66 (0.65-0.66) in the pediatric validation 2 datasets. We found significant discrimination across pediatric subcohorts of European (AUC, 95% CI, 0.60 and 0.66), African (AUC, 95% CI, 0.61 and 0.66), admixed American (AUC, 0.64 and 0.70), Southeast Asian (AUC, 0.65), and East Asian (AUC, 0.73) ancestry. Pediatric participants with the top 5% PRS had 2.80 to 5.82 increased odds of asthma compared to the bottom 5% across the training, validation 1, and validation 2 cohorts when adjusted for ancestry. Phenome-wide association study analysis confirmed the strong association of the identified PRS with asthma (odds ratio, 2.71, PFDR= 3.71× 10-65) and related phenotypes. A multiancestral PRS for asthma based on Bayesian posterior genomic effect sizes identifies increased odds of pediatric asthma.

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort.

Variable penetrance and late-onset phenotypes are key challenges for classifying causal as well as incidental findings in inherited cardiac conditions. Allele frequencies of variants in ancestry-specific populations, along with clinical variant analysis and interpretation, are critical to determine their true significance. Here, we carefully reviewed and classified variants in genes associated with inherited cardiac conditions based on a population whole-genome sequencing cohort of 4810 Singaporeans representing Southeast Asian ancestries. Eighty-nine (1.85%) individuals carried either pathogenic or likely pathogenic variants across 25 genes. Forty-six (51.7%) had variants in causal genes for familial hyperlipidemia, but there were also recurrent variants in SCN5A and MYBPC3, causal genes for inherited arrhythmia and cardiomyopathy, which, despite previous reports, we determined to lack criteria for pathogenicity. Our findings highlight the incidence of disease-related variants in inherited cardiac conditions and emphasize the value of large-scale sequencing in specific ancestries. Follow-up detailed phenotyping and analysis of pedigrees are crucial because assigning pathogenicity will significantly affect clinical management for individuals and their family members.

NMOSD and MS prevalence in the Indigenous populations of Australia and New Zealand.

We studied the prevalence of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in Indigenous populations of Australia and New Zealand with the aim of assessing potential differences. Cases of possible NMOSD and MS were collected from Australia and New Zealand. Clinical details, MR imaging, and serologic results were used to apply 2015 IPND diagnostic criteria for NMOSD and 2010 McDonald criteria for MS. Frequencies of self-determined ethnic ancestry were calculated for confirmed NMOSD, suspected NMOSD, and MS. Prevalence rates for NMOSD and MS according to ancestry were compared. There were 75 cases with NMOSD, 89 with suspected NMSOD, and 101 with MS. NMOSD cases were more likely to have Asian, Indigenous, or Other ancestry compared to suspected NMOSD or MS. There were no differences in the clinical phenotype of NMOSD seen in Indigenous compared to European ancestry populations. Per 100,000, the prevalence estimate for NMOSD in people with Māori ancestry was 1.50 (95% CI 0.52-2.49) which was similar to those with Asian ancestry 1.57 (95% CI 1.15-1.98). NMOSD prevalence in Australian Aboriginal and Torres Strait Islander populations was 0.38 (95% CI 0.00-0.80) per 100,000. The prevalence of NMOSD in the Māori population is similar to South East Asian countries, reflecting their historical origins. The prevalence of MS in this group is intermediate between those with South East Asian and European ancestry living in New Zealand. Both NMOSD and particularly MS appear to be uncommon in the Indigenous populations of Australia.

Homozygous variant p. Arg90His in NCF1 is associated with early-onset Interferonopathy: a case report

BackgroundBiallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient.Case presentationA 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient’s cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers.ConclusionHomozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity.

Isolation and Genomic Characterization of Echovirus 11 from faeces of a Non-Human Primate in Nigeria.

We recently investigated the presence of enteroviruses (EVs) in non-human primates (NHPs) in Northern Nigeria and documented the presence of EV-A76 of South-East Asian ancestry in an NHP. In this study, we go further to ask if we could also find EVs in NHPs indigenous to the forested South-south Nigeria. Fresh faecal samples were collected from the floor of 10 cages housing NHPs in Cross River Nigeria, re-suspended in PBS and subjected to RNA extraction, cDNA synthesis, PanEnt 5'-UTR and PanEnt VP1 PCR assays. None of the samples was positive for the PanEnt VP1 assay, but one sample was positive for PanEnt 5'-UTR PCR. This sample was subsequently inoculated into RD cell line, produced CPE and the isolate analysed by PCR assays, next-generation whole genome sequencing and passage in four different cell lines showing replication in two of them. Analysis of the complete genome of the isolate identified it as an Echovirus 11 (E11) and revealed a recombinant genomic structure. Phylogenetic analysis showed that the E11 NHP strain was related to human clinical isolates suggesting a zoonotic behaviour. We describe the first isolation and complete genome characterization of an E11 obtained from an NHP in Nigeria having zoonotic potential.

Detecting Genetic Ancestry and Adaptation in the Taiwanese Han People.

The Taiwanese people are composed of diverse indigenous populations and the Taiwanese Han. About 95% of the Taiwanese identify themselves as Taiwanese Han, but this may not be a homogeneous population because they migrated to the island from various regions of continental East Asia over a period of 400 years. Little is known about the underlying patterns of genetic ancestry, population admixture, and evolutionary adaptation in the Taiwanese Han people. Here, we analyzed the whole-genome single-nucleotide polymorphism genotyping data from 14,401 individuals of Taiwanese Han collected by the Taiwan Biobank and the whole-genome sequencing data for a subset of 772 people. We detected four major genetic ancestries with distinct geographic distributions (i.e., Northern, Southeastern, Japonic, and Island Southeast Asian ancestries) and signatures of population mixture contributing to the genomes of Taiwanese Han. We further scanned for signatures of positive natural selection that caused unusually long-range haplotypes and elevations of hitchhiked variants. As a result, we identified 16 candidate loci in which selection signals can be unambiguously localized at five single genes: CTNNA2, LRP1B, CSNK1G3, ASTN2, and NEO1. Statistical associations were examined in 16 metabolic-related traits to further elucidate the functional effects of each candidate gene. All five genes appear to have pleiotropic connections to various types of disease susceptibility and significant associations with at least one metabolic-related trait. Together, our results provide critical insights for understanding the evolutionary history and adaption of the Taiwanese Han population.

Upholding Success: Asian Americans, Egg Freezing, and the Fertility Paradox

ABSTRACT Asian American women are turning to oocyte cryopreservation (egg freezing) at rates higher than would be expected, given that Asian Americans make up less than six percent of the total United States population. Based on ethnographic interviews with 23 women of East, Southeast, and South Asian ancestry, we examine the “fertility paradox” faced by highly educated Asian American professional women. Despite achieving multiple “pillars of success,” these women have difficulty finding educated partners with whom to pursue childbearing. Egg freezing offers feelings of empowerment and relief from pressure for Asian American women, holding open the possibility of future biogenetic motherhood.

Abstract 4600: Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort

Abstract Introduction There is limited diversity in current hereditary multi-gene testing data-sets, leading to greater challenges in accurate variant classification. To address this, a collaboration between 3 Singapore-based healthcare organizations (Tan Tock Seng Hospital, National Cancer Centre Singapore and Lucence Diagnostics) pooled results from patients of East Asian, Southeast Asian and South Asian ancestry, representing over 60% of the world's population. We hypothesized that a multi-ethnic collaboration would provide deeper understanding of cancer predisposition genes, particularly in terms of novel variants. Methods A total of 704 cancer patients of multi-ethnic Asian (SE Asian, East Asian and South Asian) ethnicity with either a history of breast, ovarian, pancreatic or prostate cancer, were tested with multi-gene panels. All patients were tested by multi-gene testing, including but not limited to BRCA1/2, PALB2 and ATM. In addition to genetic testing, the family histories of the patients were collected. All variants were classified by ACMG criteria. Chi-square testing was used for statistical analysis. Results Three sites (TTSH, NCCS, and Lucence) pooled patients selected for breast (n=458), ovarian (n=176), pancreatic (n=61) and prostate cancer (n=25). The mean and median ages were 44.9 years and 43 years, respectively. Of the 704 patients, 209 had a history of cancer in their first degree relatives, 432 did not and 63 patients did not know of any cancers in their first degree relatives. 122 of 704 patients (17.33%) had pathogenic/likely pathogenic variants in any tested risk-related gene, of which 86 were in BRCA1/2, 11 in PALB2 and 4 in ATM. Some variants were detected in more than one patient. 212 of 704 patients (30.1%) had VUSs detected in any tested risk-related gene, with 32.1% in BRCA1/2. There was a positive association between multiple-cancer status and pathogenic variants (9/22 vs 113/682, p = 0.007). Most notably, among the unique pathogenic/likely pathogenic variants in BRCA1, BRCA2, PALB2 and ATM, 10.64% (5/47), 12.9% (4/31), 30% (3/10) and 25% (1/4) respectively were novel variants, not previously reported in ClinVar (Dec 2019). Conclusion To our knowledge, this is the largest regional multi-ethnic cohort of patients with breast, ovarian, pancreatic and prostate cancer undergoing comprehensive genetic testing. Only one third of patients reported a first-degree family history suggesting that testing ought to be performed if clinical suspicion is high. Notably, 14.1% of BRCA1/BRCA2/PALB2/ATM pathogenic/likely pathogenic variants detected in our cohort were novel variants, not hitherto published in ClinVar. In conclusion, this collaboration demonstrates that testing of Asian patients can enrich global understanding of cancer predisposition gene mutations. This will improve cancer prevention, surveillance, and treatment selection for cancer patients, such as the use of PARP inhibitors for genetic defects of DNA repair. Citation Format: Jens Samol, Wei Lim Chia, Liuh Ling Goh, Matthew Myint, Min-Han Tan, Ru Jin Tay, Hao Chen, Yukti Choudhury, Ann SG Lee. Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4600.

Facial average soft tissue depth variation based on skeletal classes in Indonesian adult population: A retrospective lateral cephalometric study.

To understand the influence of three types of skeletal classes (Class I, Class II and Class III) on midline average soft tissue depth (ASTD). Lateral cephalograms of 335 pre-treatment orthodontic patients were obtained from the archive of Radiology Clinic Universitas Padjadjaran Dental Hospital Bandung Indonesia. The linear measurements of 10 midline facial landmarks ASTD and angular measurement of ANB were extracted and analysed statistically. A database of ASTD grouped by skeletal classes, specific for the Indonesian population, within the South East Asian ancestry group was obtained. A generic pattern of deeper upper lip than lower lip in class III compared to class II and conversely, deeper lower lip than upper lip in class II compared to class III, was visible in both male and female groups.

Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries

BackgroundGenetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations.MethodsWe conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls.FindingsThe risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other.InterpretationThere is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.

A nostalgic Peranakan journey in Melaka: Duo-ethnographic conversations between a Nyonya and Baba

A UNESCO World Heritage Listed historic city, Melaka embodies a vibrant multi-ethnic Asian heritage, straits-colonial legacy and cultural landscape that has been attracting tourists from within Asia and the wider world. In particular, Melaka is renowned for its rich Peranakan (Straits Chinese) cultural heritage and history. This work presents the divergent narratives of two Peranakan Chinese on a nostalgic, ancestral tourism journey in Melaka. Specifically, it explores the dimensions of nostalgia, authenticity and diaspora in cultural heritage tourism, framed within the affecting gaze of cultural, diasporic and reminiscent lenses through which we consume tourism experiences. Through our tourism lived experience and duo-ethnographic conversations, we explore our shared Southeast Asian ancestry, reflect on past traditions and question representations of our Peranakan Chinese heritage within four main themes: (1) reflective nostalgia, (2) the imagined past, (3) objective authenticity, and (4) existential authenticity.

Genomic Characterization of an Echovirus 7 Isolate of Southeast Asian Ancestry Recovered from a Child in Nigeria with Acute Flaccid Paralysis.

Here, we describe the genome of an echovirus 7 (E7) isolate of Southeast Asian ancestry recovered from a child in Nigeria with acute flaccid paralysis (AFP). The genome has 7,295 nucleotides (nt) and an open reading frame (ORF) with 2,195 amino acids.

NRG1 variant effects in patients with Hirschsprung disease

BackgroundHirschsprung disease (HSCR) is a heterogeneous genetic disorder characterized by absence of ganglion cells along the intestines resulting in functional bowel obstruction. Mutations in neuregulin 1 (NRG1) gene have been implicated in some cases of intestinal aganglionosis. This study aims to investigate the contribution of the NRG1 gene to HSCR development in an Indonesian population.MethodsWe analyzed the entire coding region of the NRG1 gene in 54 histopathologically diagnosed HSCR patients.ResultsAll patients were sporadic non-syndromic HSCR with 53/54 (98%) short-segment and 1/54 (2%) long-segment patients. NRG1 gene analysis identified one rare variant, c.397G > C (p.V133 L), and three common variants, rs7834206, rs3735774, and rs75155858. The p.V133 L variant was predicted to reside within a region of high mammalian conservation, overlapping with the promoter and enhancer histone marks of relevant tissues such as digestive and smooth muscle tissues and potentially altering the AP-4_2, BDP1_disc3, Egr-1_known1, Egr-1_known4, HEN1_2 transcription factor binding motifs. This p.V133 L variant was absent in 92 non-HSCR controls. Furthermore, the rs7834206 polymorphism was associated with HSCR by case–control analysis (p = 0.037).ConclusionsThis study is the first report of a NRG1 rare variant associated with HSCR patients of South-East Asian ancestry and provides further insights into the contribution of NRG1 in the molecular genetic pathogenesis of HSCR.

Hb Penang [β78(EF2)Leu→Pro, HBB: c.236T>C]: a Novel β-Globin Variant

We report a novel hemoglobin (Hb) variant with a β chain amino acid substitution at codon 78 (CTG>CCG) (HBB: c.236T>C), detected through prenatal screening via capillary electrophoresis (CE) in an otherwise healthy and asymptomatic 38-year-old female of Southeast Asian ancestry. The variant, named Hb Penang after the proband’s Malaysian city of origin, underwent further characterization through high performance liquid chromatography (HPLC), reversed phase HPLC, Sanger sequencing, isopropanol stability testing and isoelectric focusing (IEF).

Enterovirus-A76 of South-East Asian Ancestry in a Captive Chimpanzee (Pan troglodytes) in Jos, Nigeria

We recently detected EV-A119 and EV-B111 (previously shown to co-circulate between nonhuman primates (NHPs) and humans) in Nigerian children diagnosed with acute flaccid paralysis (AFP). This study was designed to investigate and catalogue EVs present in captive NHPs in Nigeria. Twenty-seven fecal samples collected from captive NHPs in a Wild Life Park and Zoological garden at Jos, Nigeria in April 2016 were analyzed in this study. Samples were resuspended in a phosphate buffered saline (PBS)/chloroform mixture, and the clarified supernatant was subjected to RNA extraction, cDNA synthesis, a Panenterovirus 5I-UTR assay, and three different enterovirus VP1 snPCR assays. All amplicons from the snPCR assays were sequenced, and enteroviruses identified using the enterovirus genotyping tool and phylogenetic analysis. Eight (29.63%) (two each from Chimpanzees, Patas Monkey, Mona Monkey and Baboon) of the 27 samples were positive for the 5I-UTR assay. One (3.70%) of the 27 samples was positive for the enterovirus VP1 snPCR assays in addition to its positivity by 5I-UTR assay. The same sample happens to be one of the two samples from Chimpanzees that tested positive for the 5I-UTR assay, and it was subsequently identified as EV-A76 of South-East Asia ancestry. This study documents the first recorded attempt to detect and identify enteroviruses in NHPs in Nigeria. It also reports the first detection and identification of EV-A76 in Nigeria and particularly in a NHP. It is of utmost importance that the enterovirus VP1 assays be improved to enable detection of EVs that have been detected in NHPs but yet to be described in humans.