Table 1b.

Use of the Vallée Marcotte et al. 31-SNP nutri-GRS to evaluate the TG responsiveness to dietary/supplemental EPA+DHA in males and females with overweight/obesity.

Decision domain	Judgment	Reason for judgment	Subdomains influencing judgment
Quality of evidence • Is there high or moderate quality evidence?	Yes ⊠ No □	⊕⊕⊕⊕ Strong (high-quality) evidence suggests that in adults with overweight/obesity, a 31-SNP nutri-GRS can evaluate TG responsiveness to EPA+DHA supplementation. Individuals with lower scores demonstrate greater responsiveness to EPA+DHA for TG lowering.	1 RCT and 1 single arm trial have been conducted to date (25, 26). While there was some indirectness between studies, this was limited to the type of omega-3 and group stratification. One study used EPA+DHA supplementation while the other intervened with EPA or DHA supplementation (separate) (25, 26). Group stratification differed with one study stratifying participants as responders or non-responders, and the other stratifying as responders, non-responders or adverse responders (25, 26). However, balancing these limitations with evidence of a gradient for the nutri-GRS and TG responsiveness to omega-3 supplementation as well as some evidence of a mechanism of action resulted in rating the evidence back up (5).
Balance of desirable and undesirable outcomes • Given the best estimate of typical values and preferences, are you confident that the benefits outweigh the harms and burden or vice versa?	Yes ⊠ No □	The desirable consequences are notable (such as more targeted TG management strategies for improved cardiovascular health) with minimal to no undesirable consequences.	With approximately one third of the population being categorized as a non-responder or adverse responder to omega-3 for TG lowering (25, 26), there is a risk associated with giving one-size-fits-all, population-based advice. In general, omega-3 is considered safe up to 3.0 g/day of EPA+DHA.
Values and preferences • Are you confident about the typical values and preferences and are they similar across the target population?	Yes □ No ⊠	If a patient wishes to undergo this nutrigenetic test and consents to genotyping, they should have the option to do so. The test offered to the patient should be evidence-based and ethically incorporated into practice (see quality of evidence and resource use sections).	In general, the public expresses an interest in genetic testing for personalized nutrition (45–49), especially if this testing leads to lifestyle recommendations (48, 50) and is offered by a registered dietitian or other HCP (45, 50). Moreover, there is substantial demand for genetic testing among consumers (patients) (53). However, the choice to undergo this type of genetic testing will vary from person to person and some individuals have expressed concerns (50). Given the variability that some patients would choose nutrigenetic testing over population-based advice, others would not; this variability resulted in rating down the strength of the recommendation.
Resource use • Are the resources worth the expected net benefit from following the recommendation?	Yes ⊠ No □	Resources are required for the implementation of nutrigenetic testing into practice, but several nutrigenetic testing companies exist and many HCPs are already offering this type of testing in their practice.	Nutrigenetic testing has been integrated into clinical practice for many years (53). The CPG recommendations presented herein would help to strengthen existing tests available on the market and evidence-based practice among HCPs.
Overall strength of recommendation	Weak (conditional)	The guideline panel conditionally recommends that the Vallée Marcotte et al. nutri-GRS (25, 26) can be used to evaluate TG responsiveness to 3.0 g/day of EPA+DHA in adults with overweight/obesity.
Evidence to recommendation synthesis	The quality of evidence, risk vs. benefit analysis, and resource implications suggest a strong recommendation however the variability among patients in choosing to undergo genetic testing for personalized nutrition resulted in rating down the strength of the recommendation to “weak” (conditional).