A newly identified Y chromosome gene obp-Y is required for sperm storage in female Zeugodacus tau (Diptera: Tephritidae).

In the organisms with XX/XY sex chromosomes, Y chromosome is unique to males and plays an important role in male reproductive development. The study of Y chromosome genes will contribute to the development of pest genetic prevention and control technology. In this study, we identified 9 Y chromosome genes in Zeugodacus tau (Diptera: Tephritidae), including gene 16222. Protein structure analysis showed that 16222 was highly similar to odorant binding protein, and thus gene 16222 was named obp-Y. Obp-Y knockout (KO) significantly reduced hatching rate of offspring. Sperm detection results showed that obp-Y KO did not affect sperm number in the testes or sperm transfer during mating. We further examined the storage of sperms in females, and found that sperms in females mating with wild-type males began to transfer from spermathecal ducts to the spermathecae at hour 0 after the end of mating (AEM), and at 0-24 h AEM, the sperm count in the spermathecae gradually increased. However, no sperms were observed in spermathecae of females mating with mutant males at hours 0, 4, 8, 24 and 48 AEM. In summary, this study revealed that Y chromosome gene obp-Y was necessary for the storage of sperms in females. Our findings not only provide theoretical basis for elucidating the function of the Y chromosome, but also offer a molecular target for the genetic control over Z. tau.

Analysis of the genetic diversity of Tahe red deer and population structure of Cervus elaphu/hanglu/canadensis.

The Tahe red deer is currently the largest breeding population of antlered Cervus elaphus in China. It has unique characteristics such as drought and roughage tolerance, high antler yield and early sexual maturity. It is a high-quality provenance for cultivating high-yield Cervus elaphus breeds and is also the subject of study on the origin, evolution, and classification of Cervus elaphus. The breeding quantity of Tahe red deer has decreased significantly in recent years due to the influence of feeding conditions and consumer market. This has resulted in a serious threat to its genetic resources. To provide a scientific theoretical basis for the protection of the Tahe red deer population, we performed PCR amplification and direct sequencing of the AMELY2, DBY and SRY genes of the Y chromosome, and the ND1, COX1, ATP6, ND5, Cyt b and D-loop regions of the mtDNA, and analysed their genetic diversity and population genetic structure. The results showed high haplotype diversity and low nucleotide diversity in both the Y chromosome and mtDNA genes. The phylogenetic tree and haplotype network diagram, constructed using white-lipped deer as the outgroup, indicate that Tahe red deer has two distinct ancestral types. The phylogenetic tree, based on the Cyt b gene and D-loop region, reveals that the Cervus elaphus/hanglu/canadensis is divided into three clades: western, central, and eastern. Tahe red deer, C.h.bactrianus, and C.h.hanglu are clustered in the central clade. The study results indicate that Tahe red deer has low genetic diversity and two distinct ancestor types. It is speculated that the central clade is either the earliest differentiation from the ancestor species or the closest to it.

Traces of Bronze Age globalization in East Asia: Insights from a revised phylogeography of the Y-chromosome haplogroup Q1a1a-M120.

OBJECTIVE: In this study, we aim to explore the genetic imprint of Bronze Age globalization in East Asia from a phylogeographic perspective by examining the Y-chromosome haplogroup Q1a1a-M120, and to identify key demographic processes involved in the formation of early China and the ancient Huaxia people. METHODS: Over the past few decades, we have collected the sequences of 347 Y chromosomes from the haplogroup Q1a1a-M120. These sequences were utilized to analyze and reconstruct a highly revised phylogenetic tree with age estimates. And we analyzed the geographical distribution and spatial autocorrelation of nine major sub-branches of Q1a1a-M120. Finally, we observed the expansion of Q1a1a-M120 from the beginning of the Bronze Age in East Asia, along with the continuous dissemination of its sub-lineages among East Asian populations. RESULTS: We suggest that certain sub-lineages played a significant role in the formation of states and early civilizations in China, as well as in the development of the ancient Huaxia people, who are the direct ancestors of the Han population. Overall, we propose that haplogroup Q-M120 played a role in the introduction of Bronze Age culture to the central region of East Asia. Therefore, it is haplogroup Q-M120, rather than the Western Eurasian paternal lineage, that expanded and contributed to the gene pool of the East Asian population. CONCLUSION: In summary, the globalization of the Bronze Age led to large-scale population replacement and admixture across various regions of Eurasia; our findings highlight the unique demographic processes that occurred in East Asia during this period.

Evaluating the efficacy of three Y-STRs commercial kits in degraded skeletal remains.

Y chromosome short tandem repeats (Y-STRs) typing is a useful tool in scenarios such as mass graves analysis or disaster victim identification and has become a routine analysis in many laboratories. Not many comparisons have been performed with the currently available commercial kits, much less with degraded skeletal remains. This research aims to evaluate the performance of three commercial Y-STR kits: Yfiler™ Plus, PowerPlex® Y23, and Investigator® Argus Y-28 in 63 degraded skeletal remains from mass graves. PowerPlex® Y23 yields more reportable markers and twice the RFU on average, while Yfiler™ Plus and Investigator® Argus Y-28 exhibited a similar behaviour. Additionally, Argus Y-28, which has not been tested with this kind of samples in literature before, showed a good performance. Finally, a predictive model was attempted to be developed from quantification and autosomal STR data. However, no acceptable model could be obtained. Nevertheless, good Y-STR typing results may be expected if at least 50 pg DNA input is used or 13 autosomal markers were previously obtained.

Y and Mitochondrial Chromosomes in the Heterogeneous Stock Rat Population.

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial Chromosomes. We genotyped the Y and mitochondrial Chromosomes in heterogeneous stock rats (Rattus norvegicus), an outbred population created from eight inbred strains. We identified 8 distinct Y and 4 distinct mitochondrial Chromosomes among the 8 founders. However, only two types of each nonrecombinant chromosome were observed in our modern heterogeneous stock rat population (generations 81-97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and mitochondrial Chromosomes were strongly associated with expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern heterogeneous stock rats there are no Y and mitochondrial Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and mitochondrial Chromosomes that do not appear in modern heterogeneous stock rats, nor do they address effects that may exist in other rat populations, or in other species.

A Review of Genetic Diversity Based on the Y Chromosome in the Romanian Population.

Y chromosome analysis is used in a number of practical applications, including investigations of criminal cases, establishment of paternity, searching for missing persons, studies on human migration, evolutionary research, and historical and genealogical investigations. Questions about the origin of individual ethnic groups are addressed not only through archaeological, linguistic, and ethnographic methods but also through molecular genetics methods. The study of genetic diversity in Romania is particularly interesting from several perspectives because Romania, located in Southeast Europe, is distinguished by the fact that the Carpathians and the Danube served as natural barriers against the migrations of peoples for centuries, thus influencing the genetic mixture of the population. This is relevant for understanding the history and formation of ethnic groups in the region. In addition, many ethnic minorities live in Romania, which adds an additional dimension of genetic and cultural diversity. This article aims to provide an updated picture of the genetic diversity in Romania and to highlight the significant studies carried out among the Romanian population. By analyzing the articles published in the Web of Science, Scopus, or PubMed databases, which explore genetic diversity using the Y chromosome, the aim is to better understand the current genetic panorama in Romania.

Comprehensive Analysis of Juvenile Nasopharyngeal Angiofibromas via Whole-Exome Sequencing.

INTRODUCTION: The molecular basis and mechanisms of juvenile nasopharyngeal angiofibromas (JNA) pathogenesis are still unknown. Despite being a rare and benign neoplasm, JNA is a locally aggressive and potentially destructive head and neck neoplasm, typically found in young males. The advancement of genome technologies and analytical tools has provided an unparalleled opportunity to explore the intricacy of JNA. The present study provides the first evidence of the involvement of Y-chromosome genes in JNA. METHODS: A total of 13 JNA patients at an advanced disease stage and five age-matched male controls were registered for this study. Whole-exome sequencing (WES) analysis was conducted followed by functional analysis to understand the molecular mechanism of the JNA. RESULTS: WES analysis revealed a high prevalence of mutations in 14 genes within the protein-coding, male-specific region of the Y-chromosome of young males (mean age: 13.8 ± 2.4) with JNA. These mutations, occurring at 28 distinct positions, were characterized as moderate to high impact and were prevalent in nine JNA patients but not in the control group. The most frequently mutated genes were USP9Y and UTY, followed by KDM5D, DDX3Y, and TSPY4. The expression of USP9Y, UTY, and DDX3Y was found to be co-modulated, implying their coordinated regulation as a complex. Furthermore, somatic mutations were detected in genes previously linked to JNA. CONCLUSION: The wide array of genetic mutations in the Y-chromosome male-specific region, along with the somatic alterations identified in JNA, provides novel insights into JNA pathophysiology.

Mosaic loss of Y chromosome and the association to mortality in Danish men aged 56-100 years.

Mosaic loss of the Y chromosome (mLOY) is a common somatic mutation in the blood of elderly men and several studies have found mLOY in blood cells to be associated with an increased risk of various diseases and mortality. However, most of these studies have focused on middle-aged and older adults, meaning that mLOY in extremely old individuals like centenarians is understudied. To explore mLOY across a wider age range compared to earlier studies and to specifically focus on centenarians, mLOY was estimated in 917 Danish men aged 56-100 years. We found that the percentage of men with LOY increased with age until age 85, after which it plateaued at around 40 %. Consistently, a longitudinal comparison of mLOY revealed that mLOY predominantly increased with age, although inter-individual variation was seen. Using a twin sub-sample, the broad-sense heritability of mLOY was estimated at 72 %, indicating a substantial genetic influence. Supporting previous findings, mLOY was found to associate with increased mortality across all study participants and in men younger than 80 years. In centenarians, however, a higher level of mLOY associated with better survival, most likely due to selection, although confirmation of our findings in larger studies is needed.

A retrospective analysis of 1600 infertility patients with azoospermia and severe oligozoospermia.

OBJECTIVE: This study aimed to investigate the genetic etiology of male infertility patients. METHOD: A total of 1600 male patients with infertility, including 1300 cases of azoospermia and 300 cases of severe oligozoospermia, underwent routine semen analysis, chromosomal karyotype analysis and sex hormone level testing. The Azoospermia factor (AZF) on the Y chromosome was detected using the multiple fluorescence quantitative PCR technique. Additionally, copy number variation (CNV) analysis was performed on patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF. RESULT: Chromosomal abnormalities were found in 334 cases (20.88 %) of the 1600 male infertility patients. The most common type of abnormality was sex chromosome abnormalities (18.94 %), with 47, XXY being the most frequent abnormal karyotype. The rates of chromosomal abnormalities were significantly different between the azoospermia group and the severe oligospermia group (23.69 % and 8.67 %, respectively; P<0.05). AZF microdeletions were detected in 155 cases (9.69 %), with various deletion types and AZFc region microdeletion being the most prevalent. The rates of AZF microdeletions were not significantly different between the azoospermia group and the severe oligospermia group (9.15 % and 12 %, respectively; P=0.133). In 92 patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF, the detection rate of CNV was 16.3 %. Compared to the severe oligospermia group, the azoospermia group had higher levels of FSH and LH and lower levels of T and E2, and the differences were statistically significant (P<0.05). CONCLUSIONS: Male infertility is a complex multifactorial disease, with chromosomal abnormalities and Y chromosome microdeletions being important genetic factors leading to the disease. Initial genetic testing of infertile men should include karyotyping and Y chromosome microdeletions. If necessary, CNV testing should be performed to establish a clinical diagnosis and provide individualized treatment for male infertility.

Y-chromosome analysis recapitulates key events of Mediterranean populations.

The remarkable geographical situation of the Mediterranean region, located between Europe, Africa, and Asia, with numerous migratory routes, has made this area a crucible of cultures. Studying the Y-chromosome variability is a very performant tool to explore the genetic ancestry and evaluate scenarios that may explain the current Mediterranean gene pool. Here, six Mediterranean populations, including three Balearic Islands (Ibiza, Majorca, and Minorca) and three Southern Italian regions (Catanzaro, Cosenza, and Reggio di Calabria) were typed using 23 Y-STR loci and up to 39 Y-SNPs and compared to geographically targeted key reference populations to explore their genetic relationship and provide an overview of Y-chromosome variation across the Mediterranean basin. Pairwise RST genetic distances calculated with STRs markers and Y-haplogroups mirror the West to East geographic distribution of European and Asian Mediterranean populations, highlighting the North-South division of Italy, with a higher Eastern Mediterranean component in Southern Italian populations. In contrast, the African populations from the Southern coast of the Mediterranean clustered separately. Overall, these results support the notion that migrations from Magna Graecia or the Byzantine Empire, which followed similar Neolithic and post-Neolithic routes into Southern Italy, may have contributed to maintaining and/or reinforcing the Eastern Mediterranean genetic component in Southern Italian populations.

The impact of mosaic loss of the Y chromosome (mLOY) in men of advanced age.

The Y chromosome has long been considered to be a "genetic wasteland" harboring only few genes essentially involved in male sex development and spermatogenesis. However, the discovery of mosaic loss of the Y chromosome (mLOY) in older men has led to revisiting of the potential impact of the Y chromosome on health and the pathophysiological processes of multiple diseases such as cancer, Alzheimer's disease and cardiovascular disease. Hence, developing more sensitive techniques for the detection of mLOY has become an emergent concern. In this article, we present a comprehensive review of the literature regarding mLOY. Additionally, we discuss the emerging discoveries concerning mLOY as well as the underlying mechanisms promoting disease in men of advanced age.

Complex genomic rearrangements of the Y chromosome in a premature infant.

BACKGROUND: Chromoanagenesis is an umbrella term used to describe catastrophic "all at once" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions. CASE PRESENTATION: We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis. CONCLUSION: This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.

X and Y Differences in Melanoma Survival Between the Sexes.

Marked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune-related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses or be noncoding RNAs that regulate both sex and autosomal genes involved in immune responses or tumor growth. Loss of the KDM6C and KDM5D demethylases appeared to common genes involved. The second factor appears to be the activation of androgen receptors (AR) on melanoma cells that increase their invasiveness and growth. Induction of T-cell exhaustion by AR that limits immune responses against melanoma appeared a common finding. The development of treatments to overcome effects related to gene loss on Y poses challenges, but several avenues related to AR signaling appear worthy of further study in the treatment of metastatic disease.

Seminological, Hormonal and Ultrasonographic Features of Male Factor Infertility Due to Genetic Causes: Results from a Large Monocentric Retrospective Study.

Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors.

Promoter hypermethylation of Y-chromosome gene PRKY as a potential biomarker for the early diagnosis of prostate cancer.

Aim: To develop a methylation marker of Y-chromosome gene in the early diagnosis of prostate cancer (PCa).Materials & methods: We utilized bioinformatics analysis to identify the expression and promoter methylation of Y-chromosome gene PRKY in PCa and other common malignancies. Single-center experiments were conducted to validate the diagnostic value of PRKY promoter methylation in PCa.Results:  PRKY expression was significantly down-regulated in PCa and its mechanism may be related to promoter methylation. PRKY promoter methylation is highly specific for the diagnosis of early PCa, which may be superior to prostate-specific antigen, mpMRI and other excellent molecular biomarkers.Conclusion:  PRKY promoter methylation may be a potential marker for the early and accurate diagnosis of PCa.

Developing excellent diagnostic methylation markers for #prostate cancer! Bioinformatics analysis and experimental verification revealing promoter methylation of Y-chromosome gene PRKY is helpful to identify early prostate cancer, which may be superior to other molecular biomarkers.

Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. METHODS: LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed. RESULTS: In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events. CONCLUSIONS: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

Very severe oligozoospermia with AZFc microdeletion patients may affect intracytoplasmic sperm injection clinical outcomes: A propensity score matching analysis.

Purpose: To explore whether spermatozoa from AZFc microdeletion patients affect their outcomes of intracytoplasmic sperm injection (ICSI). Methods: Eighty-five patients with AZFc microdeletion were recruited. A control group of one hundred and forty patients with severe oligozoospermia but without AZF microdeletion was selected using propensity score matching analysis with a 1:2 nearest neighbor algorithm ratio. The ICSI outcomes of the two groups were compared. Results: AZFc microdeletion had lower rates of normal fertilization (73% vs. 80%, p = 0.17) and high-quality embryos (44% vs. 58%, p = 0.07) than the control group. There was no significant difference in the clinical pregnancy rate, miscarriage rate, and live birth rate between the two groups. When the sperm concentration was <1 million/mL, the AZFc microdeletion group exhibited lower rates of fertilization (71% vs. 80%, p = 0.03), high-quality embryo (44% vs. 58%, p = 0.02), clinical pregnancy (57% vs. 76%, p = 0.02), and live birth (49% vs. 72%, p = 0.01) than the control group. However, if sperm concentration was ≥1 million/mL, no significant differences were found. Conclusion: If the sperm concentration is <1 million/mL, AZFc microdeletion do have a detrimental effect on most outcomes of ICSI.

Multiple Human Population Movements and Cultural Dispersal Events Shaped the Landscape of Chinese Paternal Heritage.

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.

YHP: Y-chromosome Haplogroup Predictor for predicting male lineages based on Y-STRs.

Human Y chromosome reflects the evolutionary process of males. Male lineage tracing by Y chromosome is of great use in evolutionary, forensic, and anthropological studies. Identifying the male lineage based on the specific distribution of Y haplogroups narrows down the investigation scope, which has been used in forensic scenarios. However, existing software aids in familial searching using Y-STRs (Y-chromosome short tandem repeats) to predict Y-SNP (Y-chromosome single nucleotide polymorphism) haplogroups, they often lack resolution. In this study, we developed YHP (Y Haplogroup Predictor), a novel software offering high-resolution haplogroup inference without requiring extensive Y-SNP sequencing. Leveraging existing datasets (219 haplogroups, 4064 samples in total), YHP predicts haplogroups with 0.923 accuracy under the highest haplogroup resolution, employing a random forest algorithm. YHP, available on Github (https://github.com/cissy123/YHP-Y-Haplogroup-Predictor-), facilitates high-resolution haplogroup prediction, haplotype mismatch analysis, and haplotype similarity comparison. Notably, it demonstrates efficacy in East Asian populations, benefiting from training data from eight distinct East Asian ethnic populations. Moreover, it enables seamless integration of additional training sets, extending its utility to diverse populations.