Trans-ethnic meta-analysis of white blood cell phenotypes.
نویسندگان
چکیده
White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.
منابع مشابه
Elevated white blood cell counts and risk of metabolic syndrome: a dose-response meta-analysis
Background and Aim: Elevated white blood cell count has been a known risk factor for cardiovascular diseases. Cardiometabolic diseases have some risk factors in common. Therefore, we assessed the association between elevated white blood cell counts and risk of metabolic syndrome using dose-response meta-analysis method. Materials & Methods: We searched for observational studies including white ...
متن کاملInfluence of Genetic Variants in EGF and Other Genes on Hematological Traits in Korean Populations by a Genome-Wide Approach
Hematological traits are important health indicators and are used as diagnostic clinical parameters for human disorders. Recently, genome-wide association studies (GWAS) identified many genetic loci associated with hematological traits in diverse ethnic groups. However, additional GWAS are necessary to elucidate the breadth of genetic variation and the underlying genetic architecture represente...
متن کاملHematological profile change in radiation field workers
Objectives: This study focuses on the hematological parameters change and age in radiation field workers. The study aimed to identify the effect of radiation on hematological parameters and their relation to age and duration of the experience in radiation field workers. Material and Methods: This study was conducted in the Physiology research center in collaboration with thalassemia and hemogl...
متن کاملPresenting Clinical and Laboratory Data of Childhood Acute Lymphoblastic Leukemia
Abstract Background Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL) constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. The objectives of the present study were to assess frequency of presenting symptoms, laboratory data, immune ph...
متن کاملMulti-ethnic fine-mapping of 14 central adiposity loci.
The Genetic Investigation of Anthropometric Traits (GIANT) consortium identified 14 loci in European Ancestry (EA) individuals associated with waist-to-hip ratio (WHR) adjusted for body mass index. These loci are wide and narrowing the signals remains necessary. Twelve of 14 loci identified in GIANT EA samples retained strong associations with WHR in our joint EA/individuals of African Ancestry...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Human molecular genetics
دوره 23 25 شماره
صفحات -
تاریخ انتشار 2014