Interventional Testing of Gene-environment Interactions Via the Verifomics Mobile Application

The study is composed of multiple interventions which will last between 2 and 6 months that
evaluate a suite of predictions about the way that a given environmental factor impacts a
specific health outcome based on genetic information obtained from direct-to-consumer
genotyping providers (AncestryDNA and 23andMe). Substances of interest include foods,
nutritional supplements and non-invasive medical devices.

A minimum of 500 subjects will be enrolled in each intervention, and only those subjects
which are predicted to benefit from the intervention when considering all sites of interest
will be assigned to an intervention. The predictions are based on hundreds to thousands of
sites of interest at high minor allele frequency single nucleotide polymorphisms and
predictions about response are derived from the aggregate genotype at all loci considered. As
such each site of interest will have a built-in negative control group composed of
individuals enrolled in the intervention despite a genotype at that site that does not
predict a benefit. The rate that each site of interest makes correct predictions about
subject response will be compared to randomly-selected sites in order to quantify placebo
effects and establish quality metrics for the predictions.

Enrollment and participation are conducted remotely. Participants will upload genetic
information from a direct-to-consumer provider through a mobile or web browser application,
and informed consent and inclusion/exclusion criteria are accomplished remotely. After the
informed consent process, participants are asked what phenotype of interest (weight,
migraines, insomnia, etc.) they are interested in studying, their genetic information is
evaluated and they are allowed to select an intervention they qualify for based on their
genetics that they would like to participate in. Participants then answer a series of
questions to establish baseline data on relevant factors as well as evaluate the inclusion
and exclusion criteria; participants that qualify for the intervention are then given
specific instructions on how to participate, and may then use the software to report data
during the intervention. Each intervention utilizes a specific product rather than a general
class of product to reduce noise from differing sourcing, distribution, storage and
manufacturing practices.

Inclusion Criteria:

- For BMI interventions, BMI > 25

- For headache interventions, more than 2 headache-days per month

- For insomnia interventions, at least one day of self-reported poor sleep per week

- For rhinitis interventions, more than 2 days with symptoms per month

- For joint pain interventions, at least one day of self-reported joint pain per week

Exclusion Criteria:

- Women who are pregnant, nursing or attempting to become pregnant

- Immediately life-threatening disease

- Current use of nutritional supplements of interest (excluded from those interventions
to prevent overdose)

- For spinach interventions, gout