Table 1a.

APOE (rs429358 and rs7412) genetic testing to evaluate the TG responsiveness to dietary/supplemental EPA+DHA in males.

Decision domain	Judgment	Reason for judgment	Subdomains influencing judgment
Quality of evidence • Is there high or moderate quality evidence?	Yes ⊠ No □	⊕⊕⊕⊖ Strong (moderate-quality) evidence suggests that adult males (but not females) with the APOE-E3/E4 or E4/E4 genotype (rs429358, rs7412) experience significant reductions in TG in response to 0.7–3.7 g/day of EPA and/or DHA. Higher dosages may have greater TG lowering effects.	4 RCTs and 5 single arm trials have been conducted to date (16–24). Serious indirectness, including differences in age, omega-3 dosage and type (even when considering studies with male study samples separate from male + female study samples), as well as some differences in the results led to rating down the quality of evidence. However, evidence of a dose-response gradient and plausible mechanism of action strengthened the quality of evidence (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 while 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. There is often a cost for patients, and HCPs should be adequately trained, particularly with respect to the caveats associated with APOE genetic testing.	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 (and thus patient outcomes).
Overall strength of recommendation	Weak (conditional)	The guideline panel conditionally recommends that nutrigenetic testing for TG responsiveness to EPA and/or DHA omega-3s can be based on genetic testing of APOE SNPs (rs429358, rs7412) in adult male patients (but not females).
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).