RESUMEN
BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.
Asunto(s)
Adiposidad/genética , Población Negra/genética , Variación Genética , Población Blanca/genética , Adulto , Distribución de la Grasa Corporal , Femenino , Predisposición Genética a la Enfermedad/etnología , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Obesidad Abdominal/etnología , Obesidad Abdominal/genética , Polimorfismo de Nucleótido Simple/genética , Relación Cintura-CaderaRESUMEN
A novel method for detection and identification of specific alleles has been developed utilizing immobilized mismatch binding protein (IMBP). The assay involves the use of biotin-labeled probes, which are prepared by PCR amplification of cloned fragments with known sequence. The use of probes avoids many of the problems associated with the extreme sensitivity of IMBP assays to errors in PCR amplification. The method can be used to monitor PCR fidelity and to genotype both diploid and haploid organisms and has been used to distinguish rifampicin-sensitive and -resistant strains of Mycobacterium tuberculosis and to detect and distinguish two alleles of the sheep prion protein gene involved in susceptibility to scrapie.