Displaying publications 61 - 80 of 305 in total

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  1. Evaluation of novel Parkinson's disease candidate genes in the Chinese population
    Chew EGY, Liany H, Tan LCS, Au WL, Prakash KM, Annuar AA, et al.
    Neurobiol Aging, 2019 02;74:235.e1-235.e4.
    PMID: 30337193 DOI: 10.1016/j.neurobiolaging.2018.09.013
    Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  2. Fulltext Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters
    Lim SY, Lim JL, Ahmad-Annuar A, Lohmann K, Tan AH, Lim KB, et al.
    Neurodegener Dis, 2020;20(1):39-45.
    PMID: 32580205 DOI: 10.1159/000508131
    Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  3. Distribution of the FcgammaRIIIa 176 F/V polymorphism amongst healthy Chinese, Malays and Asian Indians in Singapore
    Chong KT, Ho WF, Koo SH, Thompson P, Lee EJ
    Br J Clin Pharmacol, 2007 Mar;63(3):328-32.
    PMID: 16981896
    To determine and compare the distribution of the FcgammaRIIIa 176 F/V polymorphism across three ethnically distinct populations (Chinese, Asian Indians and Malays) in Singapore.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  4. Phylogeography and ethnogenesis of aboriginal Southeast Asians
    Hill C, Soares P, Mormina M, Macaulay V, Meehan W, Blackburn J, et al.
    Mol Biol Evol, 2006 Dec;23(12):2480-91.
    PMID: 16982817
    Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula approximately 4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  5. Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry
    Lim JL, Ng EY, Lim SY, Tan AH, Abdul-Aziz Z, Ibrahim KA, et al.
    Neurol Sci, 2021 Oct;42(10):4203-4207.
    PMID: 33559030 DOI: 10.1007/s10072-021-05056-x
    BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry.

    METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.

    RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.

    CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  6. Fulltext Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting
    Lee CC, Kwa ALH, Apisarnthanarak A, Feng JY, Gluck EH, Ito A, et al.
    Clin Chem Lab Med, 2020 11 26;58(12):1983-1991.
    PMID: 31926074 DOI: 10.1515/cclm-2019-1122
    Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  7. Fulltext Multiplex APLP System for High-Resolution Haplogrouping of Extremely Degraded East-Asian Mitochondrial DNAs
    Kakuda T, Shojo H, Tanaka M, Nambiar P, Minaguchi K, Umetsu K, et al.
    PLoS One, 2016;11(6):e0158463.
    PMID: 27355212 DOI: 10.1371/journal.pone.0158463
    Mitochondrial DNA (mtDNA) serves as a powerful tool for exploring matrilineal phylogeographic ancestry, as well as for analyzing highly degraded samples, because of its polymorphic nature and high copy numbers per cell. The recent advent of complete mitochondrial genome sequencing has led to improved techniques for phylogenetic analyses based on mtDNA, and many multiplex genotyping methods have been developed for the hierarchical analysis of phylogenetically important mutations. However, few high-resolution multiplex genotyping systems for analyzing East-Asian mtDNA can be applied to extremely degraded samples. Here, we present a multiplex system for analyzing mitochondrial single nucleotide polymorphisms (mtSNPs), which relies on a novel amplified product-length polymorphisms (APLP) method that uses inosine-flapped primers and is specifically designed for the detailed haplogrouping of extremely degraded East-Asian mtDNAs. We used fourteen 6-plex polymerase chain reactions (PCRs) and subsequent electrophoresis to examine 81 haplogroup-defining SNPs and 3 insertion/deletion sites, and we were able to securely assign the studied mtDNAs to relevant haplogroups. Our system requires only 1×10-13 g (100 fg) of crude DNA to obtain a full profile. Owing to its small amplicon size (<110 bp), this new APLP system was successfully applied to extremely degraded samples for which direct sequencing of hypervariable segments using mini-primer sets was unsuccessful, and proved to be more robust than conventional APLP analysis. Thus, our new APLP system is effective for retrieving reliable data from extremely degraded East-Asian mtDNAs.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  8. Fulltext The last sea nomads of the Indonesian archipelago: genomic origins and dispersal
    Kusuma P, Brucato N, Cox MP, Letellier T, Manan A, Nuraini C, et al.
    Eur J Hum Genet, 2017 08;25(8):1004-1010.
    PMID: 28513608 DOI: 10.1038/ejhg.2017.88
    The Bajo, the world's largest remaining sea nomad group, are scattered across hundreds of recently settled communities in Island Southeast Asia, along the coasts of Indonesia, Malaysia and the Philippines. With a significant role in historical trading, the Bajo lived until recently as nomads, spending their entire lives on houseboats while moving long distances to fish and trade. Along the routes they traveled, the Bajo settled and intermarried with local land-based groups, leading to 'maritime creolization', a process whereby Bajo communities retained their culture, but assimilated - and frequently married into - local groups. The origins of the Bajo have remained unclear despite several hypotheses from oral tradition, culture and language, all currently without supporting genetic evidence. Here, we report genome-wide SNP analyses on 73 Bajo individuals from three communities across Indonesia - the Derawan of Northeast Borneo, the Kotabaru of Southeast Borneo and the Kendari of Southeast Sulawesi, with 87 new samples from three populations surrounding the area where these Bajo peoples live. The Bajo likely share a common connection with Southern Sulawesi, but crucially, each Bajo community also exhibits unique genetic contributions from neighboring populations.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  9. The prehistoric peopling of Southeast Asia
    McColl H, Racimo F, Vinner L, Demeter F, Gakuhari T, Moreno-Mayar JV, et al.
    Science, 2018 07 06;361(6397):88-92.
    PMID: 29976827 DOI: 10.1126/science.aat3628
    The human occupation history of Southeast Asia (SEA) remains heavily debated. Current evidence suggests that SEA was occupied by Hòabìnhian hunter-gatherers until ~4000 years ago, when farming economies developed and expanded, restricting foraging groups to remote habitats. Some argue that agricultural development was indigenous; others favor the "two-layer" hypothesis that posits a southward expansion of farmers giving rise to present-day Southeast Asian genetic diversity. By sequencing 26 ancient human genomes (25 from SEA, 1 Japanese Jōmon), we show that neither interpretation fits the complexity of Southeast Asian history: Both Hòabìnhian hunter-gatherers and East Asian farmers contributed to current Southeast Asian diversity, with further migrations affecting island SEA and Vietnam. Our results help resolve one of the long-standing controversies in Southeast Asian prehistory.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  10. Analysis of four PCR/SNaPshot multiplex assays analyzing 52 SNPforID markers
    Goodwin W, Alimat S
    Electrophoresis, 2017 04;38(7):1007-1015.
    PMID: 28008628 DOI: 10.1002/elps.201600383
    The SNPforID consortium identified a panel of 52 SNPs for forensic analysis that has been used by several laboratories worldwide. The original analysis of the 52 SNPs was based on a single multiplex reaction followed by two single-base-extension (SBE) reactions each of which was analyzed using capillary electrophoresis. The SBE assays were designed for high throughput genetic analyzers and were difficult to use on the single capillary ABI PRISM 310 Genetic Analyzer and the latest generation 3500 Genetic Analyzer, as sensitivity on the 310 was low and separation of products on the 3500 with POP-7™ was poor. We have modified the original assay and split it into four multiplex reactions, each followed by an SBE assay. These multiplex assays were analyzed using polymer POP-4™ on ABI 310 PRISM® and polymers POP-4™, POP-6™ and POP-7™ on the 3500 Genetic Analyzer. The assays were sensitive and reproducible with input DNA as low as 60 pg using both the ABI 310 and 3500. In addition, we found that POP-6™ was most effective with the 3500, based on the parameters that we assessed, achieving better separation of the small SBE products; this conflicted with the recommended use of POP-7™ by the instrument manufacturer. To support the use of the SNP panel in casework in Malaysia we have created an allele frequency database from 325 individuals, representing the major population groups within Malaysia. Population and forensic parameters were estimated for all populations and its efficacy evaluated using 51 forensic samples from challenging casework.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  11. Fulltext Discerning the Origins of the Negritos, First Sundaland People: Deep Divergence and Archaic Admixture
    Jinam TA, Phipps ME, Aghakhanian F, Majumder PP, Datar F, Stoneking M, et al.
    Genome Biol Evol, 2017 08 01;9(8):2013-2022.
    PMID: 28854687 DOI: 10.1093/gbe/evx118
    Human presence in Southeast Asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the "First Sundaland People." To understand the relationship between these Negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  12. Molecular Characterisation of α- and β-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia
    Koh DXR, Raja Sabudin RZA, Mohd Yusoff M, Hussin NH, Ahmad R, Othman A, et al.
    Ann. Hum. Genet., 2017 Sep;81(5):205-212.
    PMID: 28620953 DOI: 10.1111/ahg.12201
    Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and β-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and β-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (αCS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (αCd59 α), initiation codon (ATG>A-G) (αIniCd α), two-gene deletion (-SEA ), and single-gene 3.7-kb deletion (-α3.7 ). For β-thalassaemia, there were Cd26 (G>A) Hb E (βE ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (βCd19 ), and IVS 1-5 (G>C) (βIVS 1-5 ).
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  13. Fulltext Forensic characterization of 15 autosomal STRs in four populations from Xinjiang, China, and genetic relationships with neighboring populations
    Zhan X, Adnan A, Zhou Y, Khan A, Kasim K, McNevin D
    Sci Rep, 2018 03 16;8(1):4673.
    PMID: 29549272 DOI: 10.1038/s41598-018-22975-6
    The Xinjiang Uyghur Autonomous Region of China (XUARC) harbors 47 ethnic groups including the Manchu (MCH: 0.11%), Mongols (MGL: 0.81%), Kyrgyz (KGZ: 0.86%) and Uzbek (UZK: 0.066%). To establish DNA databases for these populations, allele frequency distributions for 15 autosomal short tandem repeat (STR) loci were determined using the AmpFlSTR Identifiler PCR amplification kit. There was no evidence of departures from Hardy-Weinberg equilibrium (HWE) in any of the four populations and minimal departure from linkage equilibrium (LE) for a very small number of pairwise combinations of loci. The probabilities of identity for the different populations ranged from 1 in 1.51 × 1017 (MCH) to 1 in 9.94 × 1018 (MGL), the combined powers of discrimination ranged from 0.99999999999999999824 (UZK) to 0.9999999999999999848 (MCH) and the combined probabilities of paternal exclusion ranged from 0.9999979323 (UZK) to 0.9999994839 (MCH). Genetic distances, a phylogenetic tree and principal component analysis (PCA) revealed that the MCH, KGZ and UZK are genetically closer to the Han population of Liaoning and the Mongol population of Mongolia while the MGL are closer to Han, Japanese, Korean, Malaysian, Hong Kong Han and Russians living in China.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  14. Fulltext Evaluation of two short tandem repeat multiplex systems for post-haematopoietic stem cell transplantation chimerism analysis
    Ariffin H, Daud SS, Mohamed Z, Ibrahim K, Lee TF, Chong LA
    Singapore Med J, 2007 Apr;48(4):333-7.
    PMID: 17384881
    The follow-up of chimerism status after allogeneic haematopoietic stem cell transplantation (HSCT) is essential to predict successful engraftment to assess the development of graft-versus-host disease, graft rejection and disease relapse. Analysis of short tandem repeats (STR) via polymerase chain reaction is frequently used for chimerism determination. However, most commercially-available kits have been designed for forensic purposes and may not be optimal for chimerism analysis. The present study aims to identify suitable STR markers for patient-donor pairs of predominantly Malay and Chinese ethnicity using two commercially-available forensic kits.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  15. Fulltext The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium
    Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al.
    Mol Genet Genomic Med, 2019 Jun;7(6):e707.
    PMID: 31066241 DOI: 10.1002/mgg3.707
    BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.

    METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.

    RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).

    CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  16. Mutations, associated with early-onset Alzheimer's disease, discovered in Asian countries
    Bagyinszky E, Youn YC, An SS, Kim S
    Clin Interv Aging, 2016;11:1467-1488.
    PMID: 27799753
    Alzheimer's disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People's Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People's Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  17. Fulltext FineMAV: prioritizing candidate genetic variants driving local adaptations in human populations
    Szpak M, Mezzavilla M, Ayub Q, Chen Y, Xue Y, Tyler-Smith C
    Genome Biol, 2018 Jan 17;19(1):5.
    PMID: 29343290 DOI: 10.1186/s13059-017-1380-2
    We present a new method, Fine-Mapping of Adaptive Variation (FineMAV), which combines population differentiation, derived allele frequency, and molecular functionality to prioritize positively selected candidate variants for functional follow-up. We calibrate and test FineMAV using eight experimentally validated "gold standard" positively selected variants and simulations. FineMAV has good sensitivity and a low false discovery rate. Applying FineMAV to the 1000 Genomes Project Phase 3 SNP dataset, we report many novel selected variants, including ones in TGM3 and PRSS53 associated with hair phenotypes that we validate using available independent data. FineMAV is widely applicable to sequence data from both human and other species.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  18. Fulltext Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction
    Sakaue S, Hirata J, Kanai M, Suzuki K, Akiyama M, Lai Too C, et al.
    Nat Commun, 2020 03 26;11(1):1569.
    PMID: 32218440 DOI: 10.1038/s41467-020-15194-z
    The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t-SNE, PCA-t-SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population (n = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  19. Fulltext Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
    Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al.
    Nat Genet, 2022 Nov;54(11):1640-1651.
    PMID: 36333501 DOI: 10.1038/s41588-022-01213-w
    Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  20. Fulltext Molecular characterization of α- and β-thalassaemia among Malay patients
    Yatim NF, Rahim MA, Menon K, Al-Hassan FM, Ahmad R, Manocha AB, et al.
    Int J Mol Sci, 2014 May 19;15(5):8835-45.
    PMID: 24857915 DOI: 10.3390/ijms15058835
    Both α- and β-thalassaemia syndromes are public health problems in the multi-ethnic population of Malaysia. To molecularly characterise the α- and β-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and multiplexed amplification refractory mutation systems were used to study 13 α-thalassaemia determinants and 20 β-thalassaemia mutations in 28 and 40 unrelated Malays, respectively. Four α-thalassaemia deletions and mutations were demonstrated. --SEA deletion and αCSα accounted for more than 70% of the α-thalassaemia alleles. Out of the 20 β-thalassaemia alleles studied, nine different β-thalassaemia mutations were identified of which βE accounted for more than 40%. We concluded that the highest prevalence of (α- and β-thalassaemia alleles in the Malays from Penang are --SEA deletion and βE mutation, respectively.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
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