Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates.

BACKGROUND: The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2. METHODS: This cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support or had severe complications such as septic shock or multi-organ failure. We conducted a trans-ancestry meta-analysis GWAS of European (n=302), American (n=102), South Asian (n=99), and East Asian (n=107) ancestry populations. We also carried out comprehensive post-GWAS analysis, including enrichment of SNP associations in tissues and cell-types, expression quantitative trait loci and differential expression analysis. FINDINGS: Eight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10-7), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10-6), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10-6), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10-6), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10-6), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10-6), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10-6), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10-6). The genes are expressed in the lung, associated to tumour progression, emphysema, airway obstruction, and surface tension within the lung, as well as an association to T-cell-mediated inflammation and the production of inflammatory cytokines. INTERPRETATION: We have discovered eight highly plausible genetic association with hospitalized cases in COVID-19. Further studies must be conducted on worldwide population genetics to facilitate the development of population specific therapeutics to mitigate this worldwide challenge. FUNDING: This review was commissioned as part of a project to study the host cell receptors of coronaviruses funded by Khalifa University's CPRA grant (Reference number 2020-004).

The legacy of the Human Genome Project.

The initiative forever altered biomedicine, but work remains to fulfill its true potential.

Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations.

The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.

Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon.

Estimates show that 5-10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population.

Gene panel screening for insight towards breast cancer susceptibility in different ethnicities.

African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.O.P. (Breast, Ovarian, and Prostate cancer). Upon sequencing and bioinformatic processing, rare coding variants in 14 cancer susceptibility genes were categorized according to the American College of Medical Genetics guidelines and compared between ethnicities. Overall, 107 different variants were identified, the majority of which were benign/likely benign. A pathogenic/likely pathogenic variant was detected in 8.6% and 6.5% of African American and European American cases, respectively, which was not statistically significant. However, African Americans were more likely to have at least one variant of uncertain significance (VUS; p-value 0.006); they also had significantly more VUSs in BRCA1/2 compared to European Americans (p-value 0.015). Additionally, 51.4% of African Americans and 32.3% of European Americans harbored multiple rare variants, and African Americans were more likely to have at least one VUS and one benign/likely benign variant (p-value 0.032), as well as multiple benign/likely benign variants (p-value 0.089). Moreover, of the 15 variants detected in multiple breast cancer cases, ATM c.2289T>C (p.F763L), a VUS, along with two likely benign variants, BRCA2 c.2926_2927delinsAT (p.S976I) and RAD51D c.251T>A (p.L84H), were determined to be associated with African American breast cancer risk when compared to ethnic-specific controls. Ultimately, B.O.P. screening provides essential insight towards the variant contributions in clinically relevant cancer susceptibility genes and differences between ethnicities, stressing the need for future research to elucidate inherited breast cancer risk.

Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components

BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

Mapping a route to Indigenous engagement in cancer genomic research.

Precision oncology guided by genomic research has an increasingly important role in the care of people with cancer. However, substantial inequities remain in cancer outcomes of Indigenous peoples, including Indigenous Maori in Aotearoa New Zealand (New Zealand). These inequities will be perpetuated unless deliberate steps are taken to include Indigenous peoples in all parts of cancer research-as research participants, in research leadership, and in research governance. This approach is especially important when there have been historical breaches of trust that have discouraged their participation in health research. This Personal View describes a precision oncology research roadmap for neuroendocrine tumour research, which seeks to reflect the values of New Zealand's Indigenous Maori people. This roadmap includes facilitating ongoing dialogue, Maori leadership, reciprocity, agreed kawa (guiding principles), tikanga (cultural protocols), and honest monitoring of what is and what is not being achieved. We challenge cancer researchers worldwide to generate locally appropriate roadmaps that honestly assess their practices to benefit Indigenous people internationally.

The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries.

BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history and cultural practices characterizing these regions, often involving consanguinity and inbreeding, plausibly led to the accumulation of population-specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs in these locales, a search in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data. We identified 232 PSVs in BRCA1 and 239 in BRCA2 in 25 of 33 countries surveyed. Common PSVs that were detected in four or more countries were c.5266dup (p.Gln1756Profs), c.181T>G (p.Cys61Gly), c.68_69del (p.Glu23Valfs), c.5030_5033del (p.Thr1677Ilefs), c.4327C>T (p.Arg1443Ter), c.5251C>T (p.Arg1751Ter), c.1016dup (p.Val340Glyfs), c.3700_3704del (p.Val1234Glnfs), c.4065_4068del (p.Asn1355Lysfs), c.1504_1508del (p.Leu502Alafs), c.843_846del (p.Ser282Tyrfs), c.798_799del (p.Ser267Lysfs), and c.3607C>T (p.Arg1203Ter) in BRCA1 and c.2808_2811del (p.Ala938Profs), c.5722_5723del (p.Leu1908Argfs), c.9097dup (p.Thr3033Asnfs), c.1310_1313del (p. p.Lys437Ilefs), and c.5946del (p.Ser1982Argfs) for BRCA2. Notably, some mutations (e.g., p.Asn257Lysfs (c.771_775del)) were observed in unrelated populations. Thus, seemingly genotyping recurring BRCA PSVs in specific populations may provide first pass BRCA genotyping platform.

An Interactive Resource to Probe Genetic Diversity and Estimated Ancestry in Cancer Cell Lines.

Recent work points to a lack of diversity in genomics studies from genome-wide association studies to somatic (tumor) genome analyses. Yet, population-specific genetic variation has been shown to contribute to health disparities in cancer risk and outcomes. Immortalized cancer cell lines are widely used in cancer research, from mechanistic studies to drug screening. Larger collections of cancer cell lines better represent the genomic heterogeneity found in primary tumors. Yet, the genetic ancestral origin of cancer cell lines is rarely acknowledged and often unknown. Using genome-wide genotyping data from 1,393 cancer cell lines from the Catalogue of Somatic Mutations in Cancer (COSMIC) and Cancer Cell Line Encyclopedia (CCLE), we estimated the genetic ancestral origin for each cell line. Our data indicate that cancer cell line collections are not representative of the diverse ancestry and admixture characterizing human populations. We discuss the implications of genetic ancestry and diversity of cellular models for cancer research and present an interactive tool, Estimated Cell Line Ancestry (ECLA), where ancestry can be visualized with reference populations of the 1000 Genomes Project. Cancer researchers can use this resource to identify cell line models for their studies by taking ancestral origins into consideration.

Genetics of Obesity in Diverse Populations.

PURPOSE OF REVIEW: The prevalence of obesity continues to rise, fueling a global public health crisis characterized by dramatic increases in type 2 diabetes, cardiovascular disease, and many cancers. In the USA, several minority populations, who bear much of the obesity burden (47% in African Americans and Hispanic/Latinos, compared to 38% in European descent groups), are particularly at risk of downstream chronic disease. Compounding these disparities, most genome-wide association studies (GWAS)-including those of obesity-have largely been conducted in populations of European or East Asian ancestry. In fact, analysis of the GWAS Catalog found that while the proportion of participants of non-European or non-Asian descent had risen from 4% in 2009 to 19% in 2016, African-ancestry participants are still just 3% of GWAS, Hispanic/Latinos are < 0.5%, and other ancestries are < 0.3% or not represented at all. This review summarizes recent developments in obesity genomics in US minority populations, with the goal of reducing obesity health disparities and improving public health programs and access to precision medicine. RECENT FINDINGS: GWAS of populations with the highest burden of obesity are essential to narrow candidate variants for functional follow-up, to identify additional ancestry-specific variants that contribute to individual genetic susceptibility, and to advance both public health and precision medicine approaches to obesity. Given the global public health burden posed by obesity and downstream chronic conditions which disproportionately affect non-European populations, GWAS of obesity-related traits in diverse populations is essential to (1) locate causal variants in GWAS-identified regions through fine mapping, (2) identify variants which influence obesity across ancestries through generalization, and (3) discover novel ancestry-specific variants which may be low frequency in European populations but common in other groups. Recent efforts to expand obesity genomic studies to understudied and underserved populations, including AAAGC, PAGE, and HISLA, are working to reduce obesity health disparities, improve public health, and bring the promise of precision medicine to all.

Methylation and MicroRNA Profiling to Understand Racial Disparities of Prostate Cancer.

Prostate cancer is a serious disease in terms of its high incidence and mortality rate in the USA and around the world. The prostate specific antigen (PSA) has been used for prostate cancer diagnosis and follow-up of treatment but a number of challenges remain. Epigenetic biomarkers, especially methylation and microRNA (miR) biomarkers provide an opportunity for diagnosis, prognosis, and recurrence of prostate cancer. Differential global methylation has shown some promising results. In this chapter, the emphasis is given on those biomarkers which can be assayed noninvasively in a prospective study and in a clinic. Challenges in the field, especially the validation of potential biomarkers, and their potential solutions are provided in this chapter.

Prospective Study of Cancer Genetic Variants: Variation in Rate of Reclassification by Ancestry.

Background: In germline genetic testing, variants from understudied ancestries have been disproportionately classified as being of uncertain significance. We hypothesized that the rate of variant reclassification likewise differs by ancestry. Methods: Nonbenign variants in actionable genes were collected from consenting subjects undergoing genetic testing at two Southern California sites from September 1996 through December 2016. Variant reclassifications were recorded as they were received, until February 2017 or reclassification to benign. Excluding duplicate variants (same ancestry, laboratory, classification), generalized linear models for the hereditary breast cancer genes (BRCA1/2) and other variants investigated whether rate of reclassification differed for seven categories of ancestry compared with non-Hispanic European. Models took into account laboratory, year, gene, sex, and current classification (handled as a time-dependent covariate) and were adjusted for multiple hypothesis testing. Results: Among 1483 nonbenign variants, 693 (46.7%) involved BRCA1/2. Overall, 268 (18.1%) variants were reclassified at least once. Few (9.7%) reclassified variants underwent a net upgrade in pathogenicity. For BRCA1/2 variants, reclassification rates varied by ancestry and increased over time, more steeply for ancestries with lower initial rates (African, Ashkenazi, Chinese) than for ancestries whose initial rates were high (Middle Eastern) or similar to non-Hispanic European (non-Chinese Asian, Native American, Hispanic). In contrast, reclassification rates of non-BRCA1/2 variants did not vary over time but were elevated for most minority ancestries except non-Chinese Asian and Native American. Conclusions: For nonbenign variants in cancer-related genes, the rates at which reclassifications are issued vary by ancestry in ways that differ between BRCA1/2 and other genes.

Glutathione S-transferase M1 and T1 null genotype frequency distribution among four tribal populations of western India.

Glutathione S transferase (GST) family is a key contributor in the detoxification mechanism of our body.Deletion of the genes within this family has been reported in the failure of detoxification system, to some extent leading to various types of cancers and other life threatening diseases. The existing data and reports on the association of null genotype of both GSTM1 and GSTT1 genes for various diseases are inconsistent. But knowledge of the polymorphic distributions of genotypes in different populations is important for investigating the risk factors in different epidemiological studies. The present study thus aims to determine thefrequency of GSTM1 and GSTT1 null genotype frequency among four tribal groups, i.e. Mina, Garasia, Damor and Saharia of western India. A comparative analysis with different tribal as well as world population has also been undertaken to have a view of its worldwide frequency distribution. Our results reveal a frequency distribution varying from 22.6% to 66.9% with respect to GSTM1gene polymorphism and from 19.1% to 33.0% with respect to GSTT1 gene in the studied populations. To the best of our knowledge this is the first report on the GSTM1and GSTT1frequency distribution among the tribal population of western India and our study shows that the Mina tribal population has the highest frequency of GSTM1.

Race-associated biological differences among luminal A and basal-like breast cancers in the Carolina Breast Cancer Study.

BACKGROUND: We examined racial differences in the expression of eight genes and their associations with risk of recurrence among 478 white and 495 black women who participated in the Carolina Breast Cancer Study Phase 3. METHODS: Breast tumor samples were analyzed for PAM50 subtype and for eight genes previously found to be differentially expressed by race and associated with breast cancer survival: ACOX2, MUC1, FAM177A1, GSTT2, PSPH, PSPHL, SQLE, and TYMS. The expression of these genes according to race was assessed using linear regression and each gene was evaluated in association with recurrence using Cox regression. RESULTS: Compared to white women, black women had lower expression of MUC1, a suspected good prognosis gene, and higher expression of GSTT2, PSPHL, SQLE, and TYMS, suspected poor prognosis genes, after adjustment for age and PAM50 subtype. High expression (greater than median versus less than or equal to median) of FAM177A1 and PSPH was associated with a 63% increase (hazard ratio (HR) = 1.63, 95% confidence interval (CI) = 1.09-2.46) and 76% increase (HR = 1.76, 95% CI = 1.15-2.68), respectively, in risk of recurrence after adjustment for age, race, PAM50 subtype, and ROR-PT score. Log2-transformed SQLE expression was associated with a 20% increase (HR = 1.20, 95% CI = 1.03-1.41) in recurrence risk after adjustment. A continuous multi-gene score comprised of eight genes was also associated with increased risk of recurrence among all women (HR = 1.11, 95% CI = 1.04-1.19) and among white (HR = 1.14, 95% CI = 1.03-1.27) and black (HR = 1.11, 95% CI = 1.02-1.20) women. CONCLUSIONS: Racial differences in gene expression may contribute to the survival disparity observed between black and white women diagnosed with breast cancer.

The Role of RNF213 4810G>A and 4950G>A Variants in Patients with Moyamoya Disease in Korea.

Although a founder variant of RNF213 4810G>A is a major genetic risk factor for moyamoya disease (MMD) in East Asians, the frequency and disease susceptibility of RNF213 variants remain largely unknown. This study investigated the mutation analysis of RNF213 (4448, 4810, 4863, and 4950) between Korean MMD and healthy controls. We performed a polymerase chain reaction-restriction fragment length polymorphism analysis. To identify the association between RNF213 gene polymorphisms and MMD disease, we performed statistical analyses such as multivariable logistic regression and Fisher's exact test. Genetic data from 117 MMD patients were analyzed and compared with 253 healthy controls. We assessed and compared single nucleotide polymorphisms of RNF213 (4448, 4810, 4863, and 4950) between MMD and control groups. We performed genome-wide association studies to investigate the genetic pathophysiology of MMD. Among the RNF213 variants (4448G>A, 4810G>A, 4863G>A, and 4950G>A), RNF213 4810G>A and 4950G>A variants were more frequent in MMD patients. In a subgroup analysis, the RNF213 4810G>A was more frequent in moyamoya disease, and the comparison with GG+AA genotype was also significantly different in moyamoya patients. These results confirm that RNF213 4810G>A and RNF213 4950G>A were more frequent in MMD patients. We have confirmed that RNF213 4810G>A and 4950G>A are strongly associated with Korean MMD in children and adults as well as for the ischemic and hemorrhagic types.

HEROD: a human ethnic and regional specific omics database.

MOTIVATION: Genetic and gene expression variations within and between populations and across geographical regions have substantial effects on the biological phenotypes, diseases, and therapeutic response. The development of precision medicines can be facilitated by the OMICS studies of the patients of specific ethnicity and geographic region. However, there is an inadequate facility for broadly and conveniently accessing the ethnic and regional specific OMICS data. RESULTS: Here, we introduced a new free database, HEROD, a human ethnic and regional specific OMICS database. Its first version contains the gene expression data of 53 070 patients of 169 diseases in seven ethnic populations from 193 cities/regions in 49 nations curated from the Gene Expression Omnibus (GEO), the ArrayExpress Archive of Functional Genomics Data (ArrayExpress), the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Geographic region information of curated patients was mainly manually extracted from referenced publications of each original study. These data can be accessed and downloaded via keyword search, World map search, and menu-bar search of disease name, the international classification of disease code, geographical region, location of sample collection, ethnic population, gender, age, sample source organ, patient type (patient or healthy), sample type (disease or normal tissue) and assay type on the web interface. AVAILABILITY AND IMPLEMENTATION: The HEROD database is freely accessible at http://bidd2.nus.edu.sg/herod/index.php. The database and web interface are implemented in MySQL, PHP and HTML with all major browsers supported. CONTACT: phacyz@nus.edu.sg.

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis.

The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G > C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p < 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G > C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G > C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.

High prevalence of W1282x mutation in cystic fibrosis patients from Karachay-Cherkessia.

Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease. The spectrum and frequency of CFTR mutations vary significantly in different populations and ethnic groups. A genetic epidemiological study was conducted in the indigenous ethnic group of people known as the Karachais. They live in the Republic of Karachay-Cherkessia, which lies in the northwest of Russia's North Caucasus region. Karachai's are Turkic-speaking and consist of 194 thousand people (approximately 40% of the population of the Republic). Molecular genetic analysis was performed in 10 unrelated Karachai families with CF patients from three districts in the Republic. A high frequency of W1282X mutation was found (18 of 20 mutant alleles): eight patients were homozygous for the W1282X mutation, and two were compound heterozygous (the second alleles were R1066C and R709X). Analysis for 13 common CF mutations in the sample of 142 healthy Karachais identified two 1677delTA and two W1282X mutation carriers. Thus, the most common CFTR mutation, F508del, was not detected among the CF patients or in healthy Karachais. The most frequent mutation among Karachai patients is W1282X (90%). Its frequency in healthy Karachais is approximately 0.007. Haplotype analysis using the CFTR intragene DNA markers IVS1CA, IVS6aGATT, IVS8CA and IVS17bCA showed that the origins of the W1282X mutation in Karachay-Cherkessia and the Eastern European part of Russia are different.