Anatolian genetic ancestry in North Lebanese populations.

Lebanon's rich history as a cultural crossroad spanning millennia has significantly impacted the genetic composition of its population through successive waves of migration and conquests from surrounding regions. Within modern-day Lebanon, the Koura district stands out with its unique cultural foundations, primarily characterized by a notably high concentration of Greek Orthodox Christians compared to the rest of the country. This study investigates whether the prevalence of Greek Orthodoxy in Koura can be attributed to modern Greek heritage or continuous blending resulting from the ongoing influx of refugees and trade interactions with Greece and Anatolia. We analyzed both ancient and modern DNA data from various populations in the region which could have played a role in shaping the current population of Koura using our own and published data. Our findings indicate that the genetic influence stemming directly from modern Greek immigration into the area appears to be limited. While the historical presence of Greek colonies has left its mark on the region's past, the distinctive character of Koura seems to have been primarily shaped by cultural and political factors, displaying a stronger genetic connection mostly with Anatolia, with affinity to ancient but not modern Greeks.

Population dynamics and genetic isolation in the Central Himalayan region: insights from Sikkim population, India.

India's rich diversity encompasses individuals from varied geographical, cultural, and ethnic backgrounds. In the field of population genetics, comprehending the genetic diversity across distinct populations plays a crucial role. This study presents significant findings from genetic data obtained from the Sikkimese population of India. Autosomal markers were crucial for evaluating forensic parameters, with a combined paternity index of 1 × 109. Notably, Penta E emerged as a distinguishing marker for individual identification in the Sikkim population. Fst genetic distance values revealed insights into genetic isolation among different groups, enhancing our understanding of population dynamics in the central Himalayan region. The NJ-based phylogenetic tree highlighted close genetic relationships, of the Sikkim population with the Nepalese population surrounding neighbouring Himalayan populations providing glimpses into common ancestry. In summary, this study contributes valuable data to population genetics and underscores the importance of genetic variation in comprehending population dynamics and forensic applications.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10-39; OR = 4.73, p = 2 × 10-10; OR = 2.3, p = 7.49 × 10-9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10-7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10-16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10-6). CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

A multi-ethnic reference panel to impute HLA classical and non-classical class I alleles in admixed samples: Testing imputation accuracy in an admixed sample from Brazil.

The MHC class I region contains crucial genes for the innate and adaptive immune response, playing a key role in susceptibility to many autoimmune and infectious diseases. Genome-wide association studies have identified numerous disease-associated SNPs within this region. However, these associations do not fully capture the immune-biological relevance of specific HLA alleles. HLA imputation techniques may leverage available SNP arrays by predicting allele genotypes based on the linkage disequilibrium between SNPs and specific HLA alleles. Successful imputation requires diverse and large reference panels, especially for admixed populations. This study employed a bioinformatics approach to call SNPs and HLA alleles in multi-ethnic samples from the 1000 genomes (1KG) dataset and admixed individuals from Brazil (SABE), utilising 30X whole-genome sequencing data. Using HIBAG, we created three reference panels: 1KG (n = 2504), SABE (n = 1171), and the full model (n = 3675) encompassing all samples. In extensive cross-validation of these reference panels, the multi-ethnic 1KG reference exhibited overall superior performance than the reference with only Brazilian samples. However, the best results were achieved with the full model. Additionally, we expanded the scope of imputation by developing reference panels for non-classical, MICA, MICB and HLA-H genes, previously unavailable for multi-ethnic populations. Validation in an independent Brazilian dataset showcased the superiority of our reference panels over the Michigan Imputation Server, particularly in predicting HLA-B alleles among Brazilians. Our investigations underscored the need to enhance or adapt reference panels to encompass the target population's genetic diversity, emphasising the significance of multiethnic references for accurate imputation across different populations.

A comprehensive whole genome database of ethnic minority populations.

China, is characterized by its remarkable ethnical diversity, which necessitates whole genome variation data from multiple populations as crucial tools for advancing population genetics and precision medical research. However, there has been a scarcity of research concentrating on the whole genome of ethnic minority groups. To fill this gap, we developed the Guizhou Multi-ethnic Genome Database (GMGD). It comprises whole genome sequencing data from 476 healthy unrelated individuals spanning 11 ethnic minorities groups in Guizhou Province, Southwest China, including Bouyei, Dong, Miao, Yi, Bai, Gelo, Zhuang, Tujia, Yao, Hui, and Sui. The GMGD database comprises more than 16.33 million variants in GRCh38 and 16.20 million variants in GRCh37. Among these, approximately 11.9% (1,956,322) of the variants in GRCh38 and 18.5% (3,009,431) of the variants in GRCh37 are entirely new and do not exist in the dbSNP database. These novel variants shed light on the genetic diversity landscape across these populations, providing valuable insights with an average coverage of 5.5 ×. This makes GMGD the largest genome-wide database encompassing the most diverse ethnic groups to date. The GMGD interactive interface facilitates researchers with multi-dimensional mutation search methods and displays population frequency differences among global populations. Furthermore, GMGD is equipped with a genotype-imputation function, enabling enhanced capabilities for low-depth genomic research or targeted region capture studies. GMGD offers unique insights into the genomic variation landscape of different ethnic groups, which are freely accessible at https://db.cngb.org/pop/gmgd/ .

Exome Sequencing: the Search for Mutations Associated with Hereditary Breast and Ovarian Cancers in the Tuvan Ethnic Group (A Pilot Study).

Whole exome sequencing of peripheral blood samples from Tuvan females diagnosed with breast and ovarian cancers (BC/OC) was performed to search for new genes involved in BC/OC pathogenesis. Considering the high cost of whole exome sequencing and study material requirements, 9 samples were selected from 61 genomic DNA samples. A mutation in the LGR4 gene (rs34804482) involved in the tumor-mediated Wnt signaling pathway and a mutation in the BRWD1 gene (rs147211854) involved in chromatin remodeling were identified in BC patients. A mutation in the CITED2 gene (rs77963348) involved in the pathogenesis of primary ovarian insufficiency was identified in a patient with OC and a history of infertility. A mutation in the PDGFRA gene (rs2291591) was identified in two BC/OC patients. LRG4, BRWD1, PDGFRA, and CITED2 germline pathogenic mutations were discovered in Tuvan women diagnosed with BC/OC for the first time.

Association Between Family History and Early-Onset Atrial Flutter Across Racial and Ethnic Groups.

BACKGROUND: Genetic and familial contributions to early-onset atrial fibrillation are described primarily in individuals of European ancestry. However, the role of racial and familial contributions in the pathogenesis of early-onset atrial flutter (EOAFL) is unclear. METHODS AND RESULTS: In this cross-sectional study, participants were enrolled prospectively from 2015 to 2021 in multiple academic centers with a diagnosis of atrial flutter (AFL) confirmed by ECG. EOAFL was defined as a diagnosis of AFL before age 66 years with no concomitant or previous diagnosis of atrial tachyarrhythmias. Family history was adjudicated through baseline questionnaires and direct family interviews about the diagnosis of atrial tachyarrhythmias, stroke, and cardiomyopathy. The primary exposure was a positive family history in first-degree relatives, and the primary outcome was the odds of EOAFL versus late-onset AFL. A total of 909 patients were enrolled. Participants with a positive family history of atrial tachyarrhythmias were younger, less likely to be of Black race, and more likely to have EOAFL. The adjusted odds ratio (OR) for EOAFL in those with a positive family history was 1.8 (95% CI, 1.1-3.0). There was an increased odds of EOAFL in those of Black race (OR, 2.1 [95% CI, 1.4-3.2]), alcohol use (OR, 1.6 [95% CI, 1.0-2.6]), and obstructive sleep apnea (OR, 1.9 [95% CI, 1.0-3.4]). Use of cardioselective ß blockers or calcium channel blockers before the diagnosis of AFL were associated with a lower odds of EOAFL (OR, 0.5 [95% CI, 0.2-0.9]). CONCLUSIONS: These findings suggest a potentially hereditary predisposition to EOAFL across race and ethnicity, warranting further study of the genetic contributions to AFL.

CD59 gene: 143 haplotypes of 22,718 nucleotides length by computational phasing in 113 individuals from different ethnicities.

BACKGROUND: CD59 deficiency due to rare germline variants in the CD59 gene causes disabilities, ischemic strokes, neuropathy, and hemolysis. CD59 deficiency due to common somatic variants in the PIG-A gene in hematopoietic stem cells causes paroxysmal nocturnal hemoglobinuria. The ISBT database lists one nonsense and three missense germline variants that are associated with the CD59-null phenotype. To analyze the genetic diversity of the CD59 gene, we determined long-range CD59 haplotypes among individuals from different ethnicities. METHODS: We determined a 22.7 kb genomic fragment of the CD59 gene in 113 individuals using next-generation sequencing (NGS), which covered the whole NM_203330.2 mRNA transcript of 7796 base pairs. Samples came from an FDA reference repository and our Ethiopia study cohorts. The raw genotype data were computationally phased into individual haplotype sequences. RESULTS: Nucleotide sequencing of the CD59 gene of 226 chromosomes identified 216 positions with single nucleotide variants. Only three haplotypes were observed in homozygous form, which allowed us to assign them unambiguously as experimentally verified CD59 haplotypes. They were also the most frequent haplotypes among both cohorts. An additional 140 haplotypes were imputed computationally. DISCUSSION: We provided a large set of haplotypes and proposed three verified long-range CD59 reference sequences, based on a population approach, using a generalizable rationale for our choice. Correct long-range haplotypes are useful as template sequences for allele calling in high-throughput NGS and precision medicine approaches, thus enhancing the reliability of clinical diagnostics. Long-range haplotypes can also be used to evaluate the influence of genetic variation on the risk of transfusion reactions or diseases.

Tracing the fine-scale demographic history and recent admixture in Hmong-Mien speakers.

The linguistic, historical, and subsistent uniqueness of Hmong-Mien (HM) speakers offers a wonderful opportunity to investigate how these factors impact the genetic structure. The genetic differentiation among HM speakers and their population history are not well characterized. Here, we generate genome-wide data from 65 Yao ethnicity samples and analyze them with published data, particularly by leveraging haplotype-based methods. We determined that the fine-scale genetic substructure of HM speakers corresponds better with linguistic classification than with geography. Particularly, parallels between serial founder events and language differentiations can be observed in West Hmongic speakers. Multiple lines of evidence indicate that ~500-year-old GaoHuaHua individuals are most closely related to West Hmongic-speaking Bunu. The strong genetic bottleneck of some HM-speaking groups, especially Bunu, could potentially be associated with their long-term practice of swidden agriculture to some degree. The inferred admixture dates for most of the HM speakers overlap with the reign of the Ming dynasty (1368-1644 CE). Besides a common genetic origin for HM speakers, their genetic ancestry is shared primarily with neighboring Han Chinese and Tai-Kadai speakers in south China. In conclusion, our analyses reveal that recent isolation and admixture events have contributed to the genetic population history of present-day HM speakers.

Analysis of the Correlation between FH and PCSK9 and APOB Gene Mutations in Han and Mongolian Populations of the Hulunbuir.

BACKGROUND: The goal of the study was to provide an individual and precise genetic and molecular biological basis for the early prevention, diagnosis, and treatment of local FH by analyzing the risk factors for the development of FH in Han and Mongolian patients in the Hulunbuir, comparing the lipid levels of FH patients of the two ethnicities, and assessing differences in mutations to two genes between the two ethnic groups. METHODS: Twenty cases each of Han Chinese and Mongolian healthy controls and fifty patients who each met the inclusion criteria from November 2021 to December 2022 in five general hospitals in Hulunbuir were selected. Multifactor logistic analysis was used to analyze the risk factors associated with the development of FH. We used t-tests to analyze statistical differences in lipid levels between the groups, and Sanger sequencing to detect the dis-tribution of common mutation sites of PCSK9 and APOB in all study subjects. The mutation rates and differences between regions and ethnic groups were summarized and compared. RESULTS: 1) Gender, age, alcohol consumption, dietary status, and a family history of FH were risk factors associated with the development of FH. 2) TC, LDL-C, and APOB were significantly higher in Mongolian cases than Han cases (p < 0.05). sdLDL-C was not statistically different between the two ethnicities (p > 0.05). 3) We detected four (8%) heterozygous mutations at the PCSK9 gene E670G mutation site in the Han case group and a total of nine (18%) mutations at this site in the Mongolian cases, including one (2%) homozygous and eight (16%) heterozygous mutations. One case of a heterozygous mutation was detected in the Mongolian control group. We detected a total of ten (20%) mutations at the APOB gene rs1367117 mutation site in the Han case group, including eight (16%) heterozygous and two (4%) homozygous mutations, 11 cases (22%) of heterozygous mutations in the Mongolian case group, two cases of heterozygous mutations in the Han control group, and one case of a heterozygous mutation in the Mongolian control group. 4) The D374Y and S127R mutation sites of PCSK9 and the R3500Q mutation site of APOB were not detected in any of the study subjects. CONCLUSIONS: The mutation sites of the PCSK9 and APOB genes in FH patients in Hulunbuir are different from other regions, and the mutation rate is higher than in other regions. Therefore, we recommend that the mutation sites of the PCSK9 and APOB genes described herein be used as clinical detection indicators to assist the diagnosis of FH in this region.

Alpha Diversity Indices as Indicators of the Variability of Gut Microbiota in Obese Adolescents of Different Ethnicities.

We compared alpha diversity indices of the intestinal microbiota in adolescents with obesity and normal body weight, taking into account their ethnicity. Intestinal biocenosis was studied by metasequencing of amplicon libraries of V3-V4 fragments of the 16S rRNA gene. The alpha diversity of the microbiota was assessed using classical and alternative indices. Statistically significant differences in intestinal microbiota were observed between Russians with obesity and Buryats with normal body weight, as well as between Russians with obesity and Buryats with obesity when assessing the Shannon-Weaver, Chao1 indices, Faith phylogenetic diversity index, ACE, Fisher, Gini coefficient, Margalef, and Menkhinik indices. It was shown that alpha diversity indices can be used to assess significance of differences and variability of the intestinal microbiota in multifactorial diseases such as obesity in adolescents; however, the scope of application of the criteria should be considered.

[Population characterization of mutations for sickle cell anemia and its treatment: One step towards personalized medicine for the disease]. / Caracterización poblacional de mutaciones relevantes para la Anemia Falciforme y su tratamiento: Un paso hacia la personalización de la enfermedad.

Sickle cell anemia (SCA) is the most common genetic disease worldwide. There are countries with massive public health programs for early detection of this condition. In the literature, several specific haplotypes or single-base polymorphic variants (SNPs) have been associated with the SCA prognosis. OBJECTIVE: To demonstrate the significant correlation of SNPs relevant to the diagnosis and prognosis of SCA among different ethnic groups. METHODOLOGY: we analyzed population frequencies and correlations of several SNPs related to the prognosis of SCA (i.e., baseline fetal hemoglobin levels), response to hydroxyurea treatment, and response to other drugs used in the SCA treatment, collected from validated genomic databases among different ethnic groups. RESULTS: The calculation of the Hardy-Weinberg equilibrium and the logistic regression was successful in classifying the ethnic groups as African (0 = 0.78, 1 = 0.89), and with a lower efficiency as American (AMR) (0 = 0.88, 1 = 0.00), East Asian (EAS) (0 = 0.80, 1 = 0.00), European (EUR) (0 = 0.79, 1 = 0.00), and South Asian (SAS) (0 = 0.80, 1 = 0.00). CONCLUSIONS: The results extend those from previous reports and show that the profile of most of the SNPs studied presented statistically significant distributions among general ethnic groups, pointing to the need to carry out massive early screening of relevant SNPs for SCA in patients diagnosed with this disease. It is concluded that the application of a broad mutation detection program will lead to a more personalized and efficient response in the treatment of SCA.

Genetic Analysis of 27 Y-STR Haplotypes in 11 Iranian Ethnic Groups.

BACKGROUND: The study of Y-chromosomal variations provides valuable insights into male susceptibility in certain diseases like cardiovascular disease (CVD). In this study, we analyzed paternal lineage in different Iranian ethnic groups, not only to identify developing medical etiology, but also to pave the way for gender-specific targeted strategies and personalized medicine in medical genetic research studies. METHODS: The diversity of eleven Iranian ethnic groups was studied using 27 Y-chromosomal short tandem repeat (Y-STR) haplotypes from Y-filer® Plus kit. Analysis of molecular variance (AMOVA) based on pair-wise RST along with multidimensional scaling (MDS) calculation and Network phylogenic analysis was employed to quantify the differences between 503 unrelated individuals from each ethnicity. RESULTS: Results from AMOVA calculation confirmed that Gilaks and Azeris showed the largest genetic distance (RST=0.35434); however, Sistanis and Lurs had the smallest considerable genetic distance (RST=0.00483) compared to other ethnicities. Although Azeris had a considerable distance from other ethnicities, they were still close to Turkmens. MDS analysis of ethnic groups gave the indication of lack of similarity between different ethnicities. Besides, network phylogenic analysis demonstrated insignificant clustering between samples. CONCLUSION: The AMOVA analysis results explain that the close distance of Azeris and Turkmens may be the effect of male-dominant expansions across Central Asia that contributed to historical and demographics of populations in the region. Insignificant differences in network analysis could be the consequence of high mutation events that happened in the Y-STR regions over the years. Considering the ethnic group affiliations in medical research, our results provided an understanding and characterization of Iranian male population for future medical and population genetics studies.

High-resolution KIR and HLA genotyping in three Chinese ethnic minorities reveals distinct origins.

Polymorphism of killer-cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands impacts the effector activity of cytotoxic NK cell and T cell subsets. Therefore, understanding the extent and implications of KIR and HLA class I genetic polymorphism across various populations is important for immunological and medical research. In this study, we conducted a high-resolution investigation of KIR and HLA class I diversity in three distinct Chinese ethnic minority populations. We studied the She, Yugur, and Tajik, and compared them with the Zhejiang Han population (Zhe), which represents the majority Southern Han ethnicity. Our findings revealed that the Tajik population exhibited the most diverse KIR copy number, allele, and haplotype diversity among the four populations. This diversity aligns with their proposed ancestral origin, closely resembling that of Iranian populations, with a relatively higher presence of KIR-B genes, alleles, and haplotypes compared with the other Chinese populations. The Yugur population displayed KIR distributions similar to those of the Tibetans and Southeast Asians, whereas the She population resembled the Zhe and other East Asians, as confirmed by genetic distance analysis of KIR. Additionally, we identified 12.9% of individuals across the three minority populations as having KIR haplotypes characterized by specific gene block insertions or deletions. Genetic analysis based on HLA alleles yielded consistent results, even though there were extensive variations in HLA alleles. The observed variations in KIR interactions, such as higher numbers of 2DL1-C2 interactions in Tajik and Yugur populations and of 2DL3-C1 interactions in the She population, are likely shaped by demographic and evolutionary mechanisms specific to their local environments. Overall, our findings offer valuable insights into the distribution of KIR and HLA diversity among three distinct Chinese ethnic minority populations, which can inform future clinical and population studies.

Toward Equitable Precision Oncology: Monitoring Racial and Ethnic Inclusion in Genomics and Clinical Trials.

PURPOSE: Ethnic diversity in cancer research is crucial as race/ethnicity influences cancer incidence, survival, drug response, molecular pathways, and epigenetic phenomena. In 2018, we began a project to examine racial/ethnic diversity in cancer research, with a commitment to review these disparities every 4 years. This report is our second assessment, detailing the present state of racial/ethnic diversity in cancer genomics and clinical trials. METHODS: To study racial/ethnic inclusion in cancer genomics, we extracted ethnic records from all data sets available at cBioPortal (n = 125,128 patients) and cancer-related genome-wide association studies (n = 28,011,282 patients) between 2018 and 2022. Concerning clinical trials, we selected studies related to breast cancer (n = 125,518 patients, 181 studies), lung cancer (n = 34,329 patients, 119 studies), and colorectal cancer (n = 40,808 patients, 105 studies). RESULTS: In cancer genomics (N = 28,136,410), 3% of individuals lack racial/ethnic registries; tumor samples were collected predominantly from White patients (89.14%), followed by Asian (7%), African American (0.55%), and Hispanic (0.21%) patients and other populations (0.1%). In clinical trials (N = 200,655), data on race/ethnicity are missing for 60.14% of the participants; for individuals whose race/ethnicity was recorded, most were characterized as White (28.33%), followed by Asian (7.64%), African (1.79), other ethnicities (1.37), and Hispanic (0.73). Racial/ethnic representation significantly deviates from global ethnic proportions (P ≤ .001) across all data sets, with White patients outnumbering other ethnic groups by a factor of approximately 4-6. CONCLUSION: Our second update on racial/ethnic representation in cancer research highlights the persistent overrepresentation of White populations in cancer genomics and a notable absence of racial/ethnic information across clinical trials. To ensure more equitable and effective precision oncology, future efforts should address the reasons behind the insufficient representation of ethnically diverse populations in cancer research.

Vaginal microbiomes show ethnic evolutionary dynamics and positive selection of Lactobacillus adhesins driven by a long-term niche-specific process.

The vaginal microbiome's composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus.

BACKGROUND: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. METHODS: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. RESULTS: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. CONCLUSION: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.

HLA allelic diversity in the Waorani population of Ecuador: Its significance to their ancestry and migration.

The Waorani, an isolated indigenous tribe in Ecuador, have long been characterized by limited genetic diversity, with few studies delving into their genetic background. Human Leukocyte Antigen (HLA) genes which are located in the human major histocompatibility complex (MHC) provides valuable insights into population evolution due to its highly polymorphic nature. However, little is known about the HLA diversity and ancestry of the Waorani population. In this study, we sequenced eight HLA genes using Next Generation Sequencing (NGS) from 134 Waorani individuals and obtained up to four-field HLA allele resolution. Cluster and phylogenetic analysis show that the Waorani are genetically distant from other Ecuador populations, but instead show genetic affinities with the Puyanawa and Terena tribes from Brazil, as well as the Mixe tribe from Mexico. The identification of alleles common within the Waorani population, previously linked to specific health conditions, notably paves the way for future association analyses. This extensive study, employing Next-Generation Sequencing (NGS) technology, significantly enriches the sparse and segmented understanding of HLA diversity in the South American region. Our findings enhance the global comprehension of human genetic diversity and underscore the value of studying indigenous populations. Such research is vital for deepening our insights into human migration patterns and evolutionary processes.

Comparison of lipidome profiles in human milk from Chinese Han and Korean ethnic groups based on high-throughput lipidomic techniques.

The composition of milk lipids varies across different ethnic sources. The lipidome profiles of Chinese Han human milk (HHM) and Chinese Korean human milk (KHM) were investigated in this study. A total of 741 lipids were identified in HHM and KHM. Twenty-eight differentially expressed lipids (DEL) were screened between the 2 milk groups; among these, 6 triacylglycerols (TG), 13 diacylglycerols (DG), 7 free fatty acids (FFA), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DEL showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DEL were further analyzed. The results demonstrated that DG, MG, and FFA showed highly positive correlations with each other (r > 0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (https://www.kegg.jp/kegg/) and Human Metabolome Database (http://www.hmdb.ca) pathways were inositol phosphate metabolism, and α-linolenic acid and linolenic acid metabolism, respectively. Major depressive disorder-related FFA (20:5) and FFA (22:6) were more abundant in KHM, whereas HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.