Genetic Research

This includes studies of healthy volunteers as well as individuals that may have a disease or condition of interest. Researchers may examine a limited set of genes or may examine the entire human genome. Policy and regulatory requirements may differ based on the extent of the sequencing and analysis performed in any given project.

1. Identifiability: A person's DNA sequence is unique (except for identical twins) and inherently identifiable, raising privacy and confidentiality concerns. The more genetic information that is obtained from an individual, the more identifiable it becomes.
2. Information Content: Genetic information can reveal susceptibility to diseases, relatedness to other individuals, and physical traits. This can have significant implications for the individual and their family.
3. Secondary Findings: These are results that are not directly related to the aims of the research, some of which may have clinical importance to the participant. The ethical obligation to inform participants about these findings is a subject of ongoing debate.

Regulatory Framework

• Genetic research must comply with the same regulations as other human subjects research, including the Common Rule and additional NIH policies specific to genomic research.
• Common Rule (2018): Requires specific disclosures in informed consent documents for research involving biospecimens, including whether whole genome sequencing may be performed.

Informed Consent

• If the research is subject to the NIH genomic data sharing policy, investigators must prospectively obtain informed consent from participants for sharing genomic data.
• Consent documents must include language informing participants about the possibility of whole genome sequencing on their biospecimens if applicable.

Practical Steps for Investigators

• Clearly describe the planned genetic analysis in the research protocol.
• Ensure informed consent documents are comprehensive, including disclosures required by the Common Rule and NIH policy.
• Address potential secondary findings and the investigator’s responsibilities regarding informing participants.

Genomic Data Sharing Policy

In 2014, NIH released the Genomic Data Sharing (GDS) policy. Effective January 25, 2015, NIH supported or conducted research, including NIH intramural research, that generates large scale human or non-human genomic is subject to the policy.

Information about the policy can be found on the Office of Science Policy website.

Data Management and Sharing Policy

In 2023, NIH released the Data Management and Sharing Policy (DMSP), which incorporates the requirements for sharing genetic and genomic research data. Investigators should be familiar with the requirements of this policy as it applies to their research.

Information about the policy can be found on the Data Management and Sharing Policy website.

Informed consent

When a study intends to conduct genomic research, it is important that the informed consent document contain information to clearly explain the nature of the research, as well as the unique risks and benefits associated with genomics. As noted above, prospective consent of the subject is a requirement of the NIH genomic data sharing policy. In the absence of consent, the investigator may not be able to obtain the necessary institutional certifications for submission of the data into dbGaP and for compliance with the NIH GDS policy. The NIH IRB has example language for the informed consent in the consent library. Please refer to this resource when drafting your informed consent document.

Key Considerations for IRB Approval

• Ensure the protocol and informed consent documents comprehensively address the inclusion of genetic or genomic research.
• Clearly outline the procedures for obtaining informed consent and handling secondary findings.
• Justify the approach to returning or not returning secondary findings.

Below is a tool for addressing genetic research in protocols and consent forms.

Secondary genomic findings refer to any finding that is not within the stated objectives of the planned research. These findings have sometimes been referred to as incidental or unanticipated findings. The OHSRP and NIH IRB consider the term secondary genomic findings to encompass those terms.

All protocols for which there is the potential for identifying secondary findings should address in the IRB approved protocol document whether results will be returned to participants. For protocols that fall within the scope of this guidance, if the return of secondary findings to human subjects is intended, a plan that is consistent with this guidance should be described in the study protocol and informed consent document. If secondary findings will not be returned, that fact along with a justification for why should be provided in the protocol and consent. Any plan to return or not return secondary findings is subject to IRB review and requires approval prior to implementation.

The IRB believes that returning clinically actionable genomic research results is ethically required when protocols build substantial clinical relationships with participants. As such, there are several available resources to assist in the process of searching for and returning secondary genomic findings. Please check with these resources before including them in your protocol.

Secondary Genomics Findings Service

The Secondary Genomics Findings Service will interrogate existing genomic data for a predefined list of clinically actionable secondary findings.  The service will also coordinate the confirmation of any results and has genetic counsellors available to return results to participants. 

Please review the following article which supports the idea of a Secondary Genomic Findings Service: A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research

NIAID Centralized Sequencing Program

The NIAID Centralized Sequencing Program is available for investigators who would benefit from a broad package of genomic research services, beyond just secondary results analysis and return.  This NIAID group collaborates with investigators to co-enroll participants on a centralized protocol and then provide sample handling; genome sequencing; bioinformatic processing; clinical review for primary, secondary, and research candidate; CLIA orthogonal confirmation; generating a written report for CRIS; genetic counseling; access to all raw files; access to genomic data portal and all data for others on the centralized protocol; data storage; dbGAP submission).  The cost is approximately $2300/pt and special projects are pursued collaboratively. For more information, contact Morgan Similuk.

NIH Intramural Sequencing Center (NISC)

If NISC is being used to sequence samples using their CLIA pipeline, secondary variants will be reviewed by a clinical molecular geneticist to determine which variants should be returned to the patient. 

Commercial Services

Several commercial services are available to analyze genomic sequence data for secondary findings in a CLIA environment.  While the NIH cannot endorse any specific companies, some examples include GeneDx, Invitae, PerkinElmer Genomics, and Prevention Genetics.