A Genome-Wide Association Study (GWAS) of Rheumatoid Arthritis (RA) Is

question 38

Multiple Choice

A genome-wide association study (GWAS) of rheumatoid arthritis (RA) is performed in a cohort of Portuguese patients, including 907 cases with RA and 1,524 controls without RA.  Logistic regression is used to test the association between RA and hundreds of thousands of loci.  These association results are then compared with data from a European GWAS cohort of 4,036 patients with RA and 6,959 patients without RA.  Finally, the Portuguese and European study results are combined into a meta-analysis.  Based on these data, the investigators identify 3 new loci that are associated with RA based on a significance level threshold of 5 × 10⁻⁸: Previous studies had identified 30 loci that accounted for <35% of disease heritability for RA.  Which of the following statements is correct regarding this study?

• A)Combining the results of the European and Portuguese studies into a meta-analysis decreases the power
• B)Logistic regression is used because there is a stepwise increase in the strength of association from Locus 1 to Locus 3
• C)The association between Locus 1 and RA in the meta-analysis is not statistically significant because the odds ratio is <1
• D)The threshold used for the p-value in the meta-analysis is 5 × 10⁻⁸ because of the large number of loci studied
• E)With this meta-analysis, the 33 identified loci account for most disease heritability in RA

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