RP-School of Public Health

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Browsing RP-School of Public Health by Author "Annaiah, K."

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    Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP
    (Public Library of Science, 2008-03) Grant, S.F.; Li, M.; Bradfield, J.P.; Kim, C.E.; Annaiah, K.; Santa, E.; Glessner, J.T.; Casalunovo, T.; Frackelton, E.C.; Otieno, George Ochieng; Shaner, J.L.; Smith, R.M.; Imielinski, M.; Eckert, A. W.; Chiavacci, R. M.; Berkowitz, R.I.; Hakonarson, H.
    Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI$95th percentile), 2,270 Caucasian controls (BMI,95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r2 = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08–1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91–1.21; P = 0.49) and of 1.31 (95% CI 1.050–1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.
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    High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications
    (Cold Spring Harbor Laboratory Press, 2009-09-19) Ochieng, Otieno, George; Shaikh, T.H.; Gai, X.; Perin, J.C.; Glessner, J.T.; Casalunovo, T.; Xie, H.; Murphy, K.; O'Hara, R.; Conlin, L.K.; D'Arcy, M.; Frackelton, E.C.; Geiger, E.A.; Haldeman-Englert, C.; Imielinski, M.; Kim, C.E.; Medne, L.; Annaiah, K.; Bradfield, J.P.; Dabaghyan, E.
    We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.
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    A Novel Susceptibility Locus for Type 1 Diabetes on Chr12q13 Identified by a Genome-Wide Association Study
    (American Diabetes Association, 2008-04) Hakonarson, H.; Qu, H.; Bradfield, J. P.; Marchand, L.; Kim, C. E.; Glessner, J. T.; Grabs, R.; Casalunovo, T.; Taback, S. P.; Frackelton, E. C.; Eckert, A. W.; Annaiah, K.; Lawson, M. L.; Otieno, George Ochieng; Santa, E.; Shaner, J. L.; Smith, R. M.; Onyiah, C. C.; Skraban, R.; Chiavacci, R. M.; Robinson, L. J.; Stanley, C. A.; Kirsch, S. E.; Devoto, M.; Monos, D. S.; Grant, S. F. A.; Polychronakos, C.
    OBJECTIVE—In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 × 10−10) and confirmed in two additional cohorts. Here we describe the results of testing, in these additional cohorts, 23 loci that were next in rank of statistical significance. RESEARCH DESIGN AND METHODS—Two independent cohorts were studied. The Type 1 Diabetes Genetics Consortium replication cohort consisted of 549 families with at least one child diagnosed with diabetes (946 total affected) and DNA from both parents. The Canadian replication cohort consisted of 364 nuclear family trios with one type 1 diabetes–affected offspring and two parents (1,092 individuals). RESULTS—One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves type 1 diabetes association with the minor allele of rs1701704 (P = 9.13 × 10−10, OR 1.25 [95% CI 1.12–1.40]). CONCLUSIONS—We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type 1 diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach
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    ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry
    (Elsevier, 2008-12) Sleiman, P. M. A.; Annaiah, K.; Imielinski, M.; Bradfield, J. P.; Kim, C. E.; Frackelton, E. C.; Glessner, J. T.; Eckert, A. W.; Otieno, F. G.; Santa, E.; Thomas, K.; Smith, R. M.; Glaberson, W.; Garris, M.; Gunnlaugsson, S.; Chiavacci, R. M.; Allen, J.; Spergel, J.; Grundmeier, R.; Grunstein, M. M.; Magnusson, M.; Bisgaard, H.; Grant, S. F. A.; Hakonarson, H.