A group of rheumatologists wants to investigate 8 candidate rheumatoid arthritis (RA) susceptibility loci to identify whether single nucleotide polymorphisms (SNPs) are associated with RA in a given population. Eight SNPs (MTHFR C677T, MTHFR A1298C, TGFβ1 T869C, TNFB A252G, VDR ApaI, VDR BsmI, VDR FokI, VDR TaqI) are tested by genotyping patients with RA (n = 105) and unrelated patients without RA (n = 80) as controls. Which of the following is the most appropriate null hypothesis for this study?

Question

A group of rheumatologists wants to investigate 8 candidate rheumatoid arthritis (RA) susceptibility loci to identify whether single nucleotide polymorphisms (SNPs) are associated with RA in a given population.  Eight SNPs (MTHFR C677T, MTHFR A1298C, TGFβ1 T869C, TNFB A252G, VDR ApaI, VDR BsmI, VDR FokI, VDR TaqI) are tested by genotyping patients with RA (n = 105) and unrelated patients without RA (n = 80) as controls.  Which of the following is the most appropriate null hypothesis for this study?

Quizplus · Accepted Answer

Explanation: 11ec2b69_bde4_03ca_8f63_d94546e4fec0_MD0005_00 A statistical hypothesis is an initial assumption, which may or may not be true, regarding population parameters (eg, mean values in two different groups) or the relationship between variables within a population (eg, association between an exposure and a disease). The null hypothesis (H₀) is a statement of no difference or no association. The alternative hypothesis (H_a) is a statement of difference or association. _a In this case, patients are initially identified based on their disease status (ie, cases: patients with rheumatoid arthritis [RA]; controls: patients without RA). The frequency of exposure (ie, 8 different single nucleotide polymorphisms [SNPs]) is subsequently compared between cases and controls; therefore, this is a case-control study. The most appropriate measure of association between exposure and disease in case-control studies is the odds ratio (OR), which represents the odds of exposure among cases relative to controls. The OR may be interpreted as follows: OR = 1.0 (null value) indicates that the odds of exposure among cases are the same as the odds of exposure among controls; therefore, exposure is not associated with the disease. OR ≠ 1.0 indicates that the odds of exposure among cases are lower (OR < 1) or higher (OR > 1) than among controls; therefore, exposure is associated with the disease. The OR is sometimes described as the odds of disease among exposed patients relative to nonexposed patients. These two OR definitions are mathematically equivalent. Because H₀ is a statement of no association, the most appropriate H₀ for this study is that the OR = 1 (Choice B). Researchers can compare patients with controls to evaluate which of the 8 SNPs are associated with RA in this population. (Choices C and D) Measures of association based on risk/incidence (eg, relative risk) are calculated in cohort studies and experimental designs, in which participants are initially selected based on exposure status (ie, exposed or nonexposed to a risk factor or treatment) and then followed over time to assess development of disease. However, in case-control studies, cases (by definition) already have the disease, so case-control studies cannot calculate and compare the risk/incidence of disease between the case and control groups. Instead, they must compare the odds of exposure (to a risk factor) between cases and controls. Educational objective: The odds ratio (OR) is a measure of association used in case-control studies. It quantifies the relationship between an exposure and a disease; its null value (ie, null hypothesis) is always OR = 1.

A Group of Rheumatologists Wants to Investigate 8 Candidate Rheumatoid