Limits...
Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

McMahon G, Ring SM, Davey-Smith G, Timpson NJ - Hum. Mol. Genet. (2015)

Bottom Line: Multiple strong associations were also observed at alleles at the HLA class II loci.The majority of these associations were explained by the lead SNP rs9271768.Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample.

View Article: PubMed Central - PubMed

Affiliation: School of Social and Community Medicine and.

No MeSH data available.


Related in: MedlinePlus

Manhattan and QQ plots. Manhattan plots with markers P < 1.E − 5 in green and P < 5.E − 8 in red indicate a strong signal on chromosome 6. QQ plots of test statistics show inflation of associations at lower P-values. A grey line indicates a straight line relationship. The genomic inflation factor (λ) is shown in text above the QQ plot. Removal of the extended MHC region resulted in a genomic inflation factor of 1.007. A dashed line indicates P = 5.E − 8.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4581602&req=5

DDV293F1: Manhattan and QQ plots. Manhattan plots with markers P < 1.E − 5 in green and P < 5.E − 8 in red indicate a strong signal on chromosome 6. QQ plots of test statistics show inflation of associations at lower P-values. A grey line indicates a straight line relationship. The genomic inflation factor (λ) is shown in text above the QQ plot. Removal of the extended MHC region resulted in a genomic inflation factor of 1.007. A dashed line indicates P = 5.E − 8.

Mentions: We carried out a genome-wide association analysis in the ALSPAC cohort and observed a single strong association peak on chromosome 6, with a complementary excess at the extremes of the test statistic distribution and an absence of systematic genome-wide inflation (Fig. 1). The lead SNP, located in the MHC class II region, was rs2760994 [odds ratio (95% CIs) 1.54 (1.37, 1.72), P-value 2.1E − 14]. A strong association signal was also observed using subjects with repeated measures collected 8 years later [odds ratio (95% CIs) 1.38 (1.21,1.57), P-value 1.2E − 06, n = 4,265]. We followed this up by conducting a genome-wide association analysis in the 1958 birth cohort and observed a complementary association signal [odds ratio (95% CIs) 1.27 (1.13, 1.44), P-value 9.6E − 05, Supplementary Material, Figs S1–S3]. After meta-analysis, the lead SNP was located 20 KB away at rs9271768 [effect allele G, odds ratio (95% CIs) 1.47 (1.35, 1.6), P-value 1.21E − 18] in an intergenic region between HLA-DRB1 and HLA-DQA1 (Table 3 and Fig. 2).Table 3.


Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

McMahon G, Ring SM, Davey-Smith G, Timpson NJ - Hum. Mol. Genet. (2015)

Manhattan and QQ plots. Manhattan plots with markers P < 1.E − 5 in green and P < 5.E − 8 in red indicate a strong signal on chromosome 6. QQ plots of test statistics show inflation of associations at lower P-values. A grey line indicates a straight line relationship. The genomic inflation factor (λ) is shown in text above the QQ plot. Removal of the extended MHC region resulted in a genomic inflation factor of 1.007. A dashed line indicates P = 5.E − 8.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581602&req=5

DDV293F1: Manhattan and QQ plots. Manhattan plots with markers P < 1.E − 5 in green and P < 5.E − 8 in red indicate a strong signal on chromosome 6. QQ plots of test statistics show inflation of associations at lower P-values. A grey line indicates a straight line relationship. The genomic inflation factor (λ) is shown in text above the QQ plot. Removal of the extended MHC region resulted in a genomic inflation factor of 1.007. A dashed line indicates P = 5.E − 8.
Mentions: We carried out a genome-wide association analysis in the ALSPAC cohort and observed a single strong association peak on chromosome 6, with a complementary excess at the extremes of the test statistic distribution and an absence of systematic genome-wide inflation (Fig. 1). The lead SNP, located in the MHC class II region, was rs2760994 [odds ratio (95% CIs) 1.54 (1.37, 1.72), P-value 2.1E − 14]. A strong association signal was also observed using subjects with repeated measures collected 8 years later [odds ratio (95% CIs) 1.38 (1.21,1.57), P-value 1.2E − 06, n = 4,265]. We followed this up by conducting a genome-wide association analysis in the 1958 birth cohort and observed a complementary association signal [odds ratio (95% CIs) 1.27 (1.13, 1.44), P-value 9.6E − 05, Supplementary Material, Figs S1–S3]. After meta-analysis, the lead SNP was located 20 KB away at rs9271768 [effect allele G, odds ratio (95% CIs) 1.47 (1.35, 1.6), P-value 1.21E − 18] in an intergenic region between HLA-DRB1 and HLA-DQA1 (Table 3 and Fig. 2).Table 3.

Bottom Line: Multiple strong associations were also observed at alleles at the HLA class II loci.The majority of these associations were explained by the lead SNP rs9271768.Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample.

View Article: PubMed Central - PubMed

Affiliation: School of Social and Community Medicine and.

No MeSH data available.


Related in: MedlinePlus