WITHDRAWN: Oxidative Balance Score and Osteoarthritis: A Multi-Omics Study Based on NHANES, RNA-seq, and Mendelian Randomization

This manuscript, which investigated the relationship between oxidative balance score and osteoarthritis using NHANES, RNA-seq, and Mendelian randomization, has been formally withdrawn by the authors due to a fundamental flaw in the study design where the reliance on unverified self-reported diagnoses introduced substantial misclassification bias that invalidates the core findings.

The Gist

Imagine this research paper as a recipe for a cake that the chefs decided to throw away before anyone could taste it. Here is the story of why, explained simply:

The Original Plan
The authors wanted to bake a "cake" to see if a specific diet score (called the Oxidative Balance Score, or OBS) was connected to a joint condition called Osteoarthritis (OA). To do this, they planned to use three different tools:

1. NHANES: A giant survey of people's health habits.
2. RNA-seq: A high-tech microscope to look at genes.
3. Mendelian Randomization: A method using genetics to guess cause-and-effect.

The Big Mistake: The "Guess-Work" Diagnosis
The problem wasn't with the ingredients (the data) or the oven (the math). The problem was how they identified who actually had the "disease" they were studying.

In this study, they asked people in the survey, "Do you have arthritis?" and took their word for it. They didn't ask for an X-ray, a doctor's note, or a physical exam to prove it.

Think of it like trying to sort a pile of fruit by asking everyone, "Is this an apple?" without ever looking at the fruit.

• Some people might say "Yes" to an apple, but they are actually holding a pear (confusing Osteoarthritis with Rheumatoid Arthritis or Gout).
• Some people might not know the difference between a bruise and a broken bone.
• The study didn't even check where the pain was (knee, hip, or hand), which is like treating a broken leg the same way as a broken finger.

Why This Ruined the Cake
The authors realized that the people who said "Yes, I have arthritis" were often those with less formal education. These individuals were more likely to be confused about their diagnosis.

This created a mix-up. Because the group labeled "sick" was actually a messy mix of different conditions and confused answers, the results couldn't tell the truth. It's like trying to measure the speed of a race car while driving on a road full of potholes and wrong turns; you can't trust the speedometer.

The Decision to Withdraw
The authors realized this wasn't a small typo that could be fixed with a quick edit. The entire foundation of their study—the definition of who was sick—was shaky. You can't fix a building if the ground it sits on is made of sand.

Because the main connection they tried to prove (between diet and arthritis) was built on this shaky ground, and because their follow-up genetic and gene studies relied on that same mistake, they decided to pull the paper entirely.

The Future Plan
They aren't giving up on the idea. They plan to go back, get a proper "ID check" for the patients (using real X-rays and doctor confirmations), and bake a new, correct cake later. For now, they are asking everyone to stop citing this version because it is no longer considered valid.

Technical Summary

Important Note: The document provided is a withdrawal notice for a preprint, not the research paper itself. Consequently, the original study's specific results, statistical values, and detailed methodological execution are not present in the text. The following summary reflects the stated intent, original scope, and the specific reasons for withdrawal as described in the notice, strictly adhering to the information available in the provided text.

Technical Summary of the Withdrawn Preprint

1. Problem Statement
The original study aimed to investigate the association between the Oxidative Balance Score (OBS) and Osteoarthritis (OA). The authors identified a critical methodological flaw in their initial approach: the diagnosis of OA relied exclusively on self-reported data from the NHANES questionnaire. The authors recognized that this approach lacked confirmation via imaging examinations or clinical physical assessments, creating a substantial risk of misclassification bias. Specifically, participants may have confused OA with other arthritic conditions (e.g., rheumatoid arthritis, gout, fibromyalgia), a confusion likely exacerbated by lower health literacy within the study population. Furthermore, the study failed to differentiate OA by anatomical site (knee, hip, hand), despite the distinct pathophysiological mechanisms associated with each.

2. Methodology (Original Design)
The study was designed as a Multi-Omics investigation integrating three primary data sources:

• NHANES Data: Used to establish the exposure (Oxidative Balance Score) and the outcome (Osteoarthritis).
• RNA-seq Data: Utilized for transcriptomic analysis to explore biological mechanisms.
• Mendelian Randomization (MR): Employed to infer causal relationships between the OBS and OA.

The core analytical framework linked the OBS to OA outcomes, followed by downstream transcriptomic and MR analyses based on this initial association.

3. Key Findings and Limitations (As Acknowledged in Withdrawal)
While the specific statistical results of the association are not detailed in the withdrawal notice, the authors explicitly conclude that the study's foundation is compromised by non-random, differential misclassification bias.

• Bias Source: The OA group contained a higher proportion of individuals with lower educational levels (15.94% with junior high school education or below) compared to the control group (9.82%). The authors posit that this demographic is more prone to misreporting diagnoses, introducing systematic bias.
• Impact on Results: This bias could either overestimate or attenuate the observed association between OBS and OA, with the direction of the bias being indeterminable post hoc.
• Heterogeneity: The lack of site-specific differentiation (knee, hip, hand) and the inclusion of non-OA arthritic conditions rendered the study population highly heterogeneous, limiting the biological interpretability of the findings.

4. Authors' Claims and Significance
The authors state that the fundamental flaw in the outcome definition (self-reported OA without validation) invalidates the entire analytical chain, including the transcriptomic and Mendelian Randomization analyses. They assert that routine revision cannot address this issue; instead, an entirely different strategy for case ascertainment is required.

5. Current Status and Future Direction
The paper is withdrawn from the preprint server. The authors do not wish for this work to be cited as a reference. They plan to redesign the study using a validated osteoarthritis case definition (incorporating imaging or clinical verification) and intend to submit a thoroughly revised version in the future. The current version is explicitly noted as not having been certified by peer review and should not be used to guide clinical practice.