NIDA Human Molecular Genetics Research: Frequently Asked Questions (FAQs)

The purposes of this document are to:

1. Clarify NIDA's data sharing policy for human molecular genetic studies of addiction for ALL applications (regardless of cost).


2. Define the NIDA Genetics Consortium, membership requirements, and the resources provided to its members.

NIDA's Data Sharing Policy for Human Molecular Genetic Studies of Addiction

Q1. How are "human molecular genetic studies of addiction" defined?

A1. Human molecular genetic studies of addiction are defined as research projects that identify chromosomal loci and genetic variation in genes that are hypothesized to be associated with abuse (including initiation) of, addiction to, or dependence on stimulants (e.g., cocaine and amphetamine), narcotics (e.g., opiates), nicotine, benzodiazepines, barbiturates, cannabis, hallucinogens, and/or multiple drugs of abuse in human beings.

Q2. Are data sharing plans expected for all human genetic studies of addiction funded by NIDA?

A2. Yes. These sharing plans must describe how data and resources generated by NIDA-funded research will be made available to other qualified individuals in a timely manner.

Q3. What are the data covered under this sharing policy?

A3. Phenotypic assessment, genotypes, and research resources such as DNA, immortalized cell lines, and/or tissue samples are covered under this sharing plan.

Q4. Are there any special expectations about data sharing for other human genetic studies of addiction vulnerability such as twin studies and adoption studies that try to characterize traits or phenotypes that are heritable?

A4. No. However, in the spirit of NIH policy on sharing data (NOT-OD-02-035) and sharing research resources [Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice, December 1999 (http://ott.od.nih.gov/NewPages/RTguide_final.html)] data generated by public funds should be made available in a timely manner.

Q5. Does the Initial Review Group or Study Section evaluate the proposed data sharing plan?

A5. For Human Molecular Genetics Research projects being considered for funding by NIDA, the Initial Review Group will be asked to provide an administrative comment about the adequacy of the sharing plan. Final approval of the plan rests with the program official.

Q6. If I apply for an administrative or competitive supplement to my grant for doing human molecular genetic studies of addiction, do I need to develop a sharing plan for the dissemination of clinical data and biomaterials (DNA)?

A6. Yes. If you receive a supplement to conduct human molecular genetics research you are expected to submit a data sharing plan.

Q7. What are the elements of an appropriate plan for sharing the dissemination data and biological materials?

A7. It is expected that the data sharing plan will specify the following elements:

• Creation of comprehensive and verified databases that contain clinical, diagnostic, pedigree structure, and genotypic information collected or produced by the grant, contract, or cooperative agreement,
• Establishment of cell lines (from which DNA will be extracted and stored) from all protocol subjects from whom blood samples have been obtained,
• A mechanism or protocol and appropriate informed consent by which all databases and biological materials (DNA samples, cell lines) can be widely searched or distributed to qualified investigators in the scientific community, and
• A timetable specifying when various elements of the database (e.g., diagnostic, assessment, or genetic data) and DNA will be available for distribution.

Q8. Do these special expectations about the dissemination of data and biological materials apply to all applications studying molecular genetics of addiction in humans?

A8. Yes. These special expectations about dissemination of data and biological materials apply to all NIDA-funded research on the molecular genetics of addiction in humans.

Q9. Is a plan to offer access to cheek swab DNA adequate to address the expectations for sharing biological materials for human molecular genetic studies of addiction?

A9. Yes. DNA obtained from cheek swabs can be used, provided that unlimited amounts of DNA of the entire genome from each individual can be generated and if necessary made available to the scientific community. Large amounts of DNA are required for repeated analyses needed to identify gene variants and chromosomal regions. Given that current cheek swab methods may not provide unlimited amounts of DNA and because high throughput genotyping of cheek swab DNA is difficult, blood remains the preferred specimen.

Q10. What is NIDA's process for approval of data sharing plans and reviewing the consistency of informed consent with the data sharing plan?

A10. The NIDA Genetics Steering Committee will review all data sharing plans for human molecular genetic studies of addiction. The committee will review the adequacy of the data sharing plan and whether the informed consent is consistent with the data sharing plan. This review will occur prior to funding new and competing continuation applications. Data sharing plans for non-competing applications will only be re-reviewed if there are proposed modifications to the original plan. The NIDA program official assigned to your application will provide final approval of the data sharing plan and determine adequacy and consistency of the informed consent with the data sharing plan. The program official will also be responsible for monitoring your compliance with the plan.

Q11. How will applicants be informed of NIDA's expectations of dissemination of data and biological materials (DNA)?

A11. This FAQ document about NIDA's policy concerning the dissemination of clinical data and biological materials (DNA) for human molecular genetics studies will be sent by NIDA to the PI for those projects whose aims are relevant to human genetic studies. This document will accompany the summary statement.

Q12. Will an acceptable plan for the dissemination of data and biological materials for human molecular genetics studies of addiction be part of the terms and conditions of the Notice of Grant Award?

A12. Yes. The approved data sharing plan shall be part of the Notice of Grant Award for any new, non-competing, or competing award. The Notice of Grant Award shall state:

"The award is contingent upon receipt of an acceptable data sharing plan within 45 days of the issuance of this Notice of Grant Award. This data sharing plan shall become part of the terms and conditions of the award."

Policy for Joining NIDA Genetics Consortium (NGC)

In September 1998, NIDA issued a Request For Applications (RFA), entitled, "Genetics of Drug Addiction Vulnerability," (RFA DA-99-003) to identify human chromosomal regions containing genes that confer susceptibility to drug abuse and addiction and related behaviors. The investigators funded under this RFA formed the initial membership of the NGC and other NIDA-funded investigators have subsequently joined. NGC members provide the NIDA Center for Genetic Studies Repository with anonymized data on family structure, age, sex, clinical status, and diagnoses, as well as blood samples from which DNA and immortalized cell lines are derived. In addition, data derived from genotyping and other genetic analyses of these clinical data and biomaterials are stored in the NIDA Center for Genetic Studies Repository. These services are provided to NGC members free of charge.

The collected data and DNA samples are required to be available for secondary data analysis for distribution by the repository to any qualified biomedical researchers at recognized biomedical research facilities. Membership in the NGC is not required to access clinical data and DNA from the NIDA Center for Genetic Studies. The data will only be made available to researchers other than the Principal Investigator 18 months after the completion of the project for which the samples were obtained initially. Those researchers requesting access to the NIDA Center for Genetic Studies database will go through an application procedure to assure appropriate use and reporting of the data (see data access FAQs).

The NGC meets twice a year to discuss issues related to the collection and analyses of data from human genetic studies on drug addiction, and members are asked to be part of the meeting. Cost for travel to the NGC is included in the PI's grant award.

Q1. Are all NIDA-funded investigators studying the human molecular genetics of addiction encouraged to join the NGC?

A1. Yes. Because of economies of scale and the need to facilitate sharing through the centralized resource, all NIDA-funded investigators are encouraged to contribute to and use the resources of the NIDA Center for Genetic Studies. By joining the NGC the applicant will:

• Increase statistical power of the studies using samples being collected;
• Enhance quality control of the data collected;
• Facilitate and enhance opportunities for collaboration;
• Have access to a data management facility to create extensively documented files at no cost;
• Have high quality cell lines produced upon receipt of blood samples;
• Have aliquots of high quality DNA extracted from the cell lines.

Q2. Does NIDA require membership in the NGC for all investigators conducting studies on the molecular genetics of drug abuse?

A2. No. NIDA strongly encourages, but does not require, membership in NGC for investigators conducting studies on human molecular genetics of drug abuse. Investigators who choose not to join the NGC will have to use resources from their grant to meet NIDA's expectations for data sharing for human molecular genetic studies described above (see Sharing Policy- A4).

Q3. What resources does NIDA make available to NGC members to assist with the dissemination of data and biological materials for human molecular genetics studies of addiction?

A3. The NIDA Center for Genetic Studies, funded through a NIDA contract, is a resource for all investigators who agree to become members of the NGC. The NIDA Center for Genetic Studies stores, in databases, clinical, diagnostic, pedigree structure, and genotypic information sent by NIDA-funded investigators who are members of the NGC. The NIDA Center for Genetic Studies creates immortalized cell lines (from which DNA is extracted and stored) from all blood samples sent by NGC members. The NIDA Center for Genetic Studies also provides a mechanism by which all databases containing clinical information and biological materials (DNA samples) can be widely searched or distributed to qualified investigators in the scientific community.

The services of the NIDA Center for Genetic Studies for shipping blood, immortalizing cell lines, and storing clinical data are free to members of the NGC. In addition, the first ten requests of 60 mg of DNA (or two 30 mg aliquots) extracted from cell lines generated from blood sent by an investigator to the NIDA Center for Genetic Studies are free to that investigator. A $50.00 fee will be charged for subsequent requests of 60 mg aliquots of DNA from each cell line.

Members wishing to gain access to the data/biomaterials contributed by other members must submit a NIDA Data Access Request. A $50.00 fee will be charged for each aliquot of 60 mg of DNA from each cell line.

Non-members may also gain access to data/biomaterials contributed by members by submitting a NIDA Data Access Request. A $100.00 fee will be charged for each aliquot of 60 mg of DNA from each cell line.

(See also FAQ about the NIDA Center for Genetic Studies for more information on the NIDA Data Access Requests).

Q4. What is membership in the NGC based on?

A4. Membership in the NGC is based upon the Principal Investigator agreeing to the following data sharing agreement*.

NIDA GENETICS CONSORTIUM
MODEL DATA SHARING PLAN

1. Whole blood samples from each subject will be sent to the NIDA Center for Genetic Studies and the Center will generate cell lines and extract DNA.
2. The NIDA Center for Genetic Studies will distribute cell lines only to the principal investigator. The principal investigator may receive a copy of each cell line, and may prepare and distribute DNA from these cell lines for himself/herself and his/her collaborators. However, resolving any discrepancies associated with DNA samples that were not prepared by the NIDA Center for Genetic Studies will be at the principal investigator's cost.
3. The data provided for each subject will be:
   
   1. Subject ID #
   2. Family ID #
   3. Site ID #
   4. Parental ID #s
   5. Sex
   6. Death status
   7. Ethnicity or geographic origin of ancestry
   8. Age and/or year of birth
   9. Twin status
   10. DSM-IIIR diagnoses
   11. DSM-IV diagnoses
   12. Instrument used to establish diagnoses
   13. Answers to all of the questions in the structured interview or, minimally, the answers to those questions from which the addiction diagnoses were established.
   14. Other descriptive information collected about the drug abuse/addiction phenotypes, such as age of onset, quantity and frequency of peak lifetime use of addictive substances, etc.
   15. Genotyping data, including the DNA marker names, description of SNPs (single nucleotide polymorphisms) or allele sizes in base pairs and corresponding frequencies, and relative map distances.
4. Data will be verified by [method] and regular updates will be provided to the NIDA Center for Genetic Studies throughout the project.
5. Verified genotyping data will be submitted to the Repository at the time that the data will be made available for sharing.
6. The approved informed consent(s) for this study are consistent with this sharing plan. Annual updates and modifications will be sent as approved by the IRB.
7. 18 months after the termination of the grant period, including extensions, or immediately upon first publication of the data, whichever comes first, the Center will distribute DNA and data to qualified investigators who have been approved by the NIDA Genetic Data Access Request Committee and who have signed the Distribution Agreement.
8. The NIDA Center will not provide pedigree structures online; instead, a printed copy of the pedigrees will be sent to approved investigators at the time that the investigator is given access to the materials and database.
9. The PI will participate in NIDA Genetic Consortium meetings, which are held 2 times per year. Cost for travel to the NGC is included in the PI's grant award.
10. Most services of the NIDA Center for Genetic Studies shall be free to investigators belonging to the NGC. Services include providing the mailers and tubes needed to ship the first 60 micrograms of blood to the Repository. The NIDA Center for Genetic Studies creates Epstein-Barr virus transformed cell lines (from which DNA is extracted and stored) from all bloods sent by NGC members. The NIDA Center for Genetic Studies also provides access to all databases containing clinical information so that biological materials (DNA) can be widely searched or distributed to qualified investigators in the scientific community. A nominal fee may be required depending on membership status and materials requested. Refer to the fee structure below.

* Minor modifications will be considered by your program official and the NIDA genetics steering committee.

Member	Data/DNA origin?	Number of Prior Requests to Access These Data/Materials	Fee	NIDA Data Access Request Needed
Yes	My Lab	10 or fewer	$0.00	No
Yes	My Lab	11 or more	$50.00	No
Yes	Other Lab	10 or Fewer	$50.00	Yes
No	Other Lab	10 or Fewer	$100.00	Yes

Q5. Is membership open to investigators funded by other NIH institutes or funding agencies?

A5. Yes, provided that the application is co-funded by NIDA.

Q6. Is NGC membership available to investigators doing other human genetic studies of addiction such as twin studies and adoption studies?

A6. No. Only investigators conducting research aimed at identifying gene variants and chromosomal regions associated with substance abuse or addiction and collecting blood samples are eligible for NGC membership. NGC meetings, however, are open to any researcher interested in attending. Please contact NIDA staff for a schedule of upcoming NGC meetings or refer to the NIDA Genetics Workgroup homepage.

Q7. May investigators apply for administrative or competitive supplements so they can join the NGC?

A7. Yes. Investigators may apply for supplemental funds to join the NGC. Supplemental funds might be requested, for example, to re-contact subjects, hire a phlebotomist, or for another purposes that would make joining the NGC possible.

Q8. Will progress on my grant be reviewed differently if I do or do not become a member of the NGC?

A8. No. Your NIDA Program Official will review and evaluate your scientific progress each year and will make recommendations for continued funding based solely on your scientific progress. Membership in the NGC will have no bearing on this evaluation process.

Q9. If I join the NGC may I decide to withdraw later?

A9. Yes. You may withdraw from the NGC after joining and make the request when you submit your non-competing renewal. You must submit a revised data sharing plan. Your revised data sharing plan must be consistent with NIDA's requirements for sharing clinical information and biomaterials (DNA). However, you will need to use extant funds to ensure that NIDA's requirements about dissemination of clinical data and biomaterials (DNA) resulting from NIDA-funded studies on the molecular genetics of drug addiction vulnerability are met. You should not expect that NIDA will provide supplemental funds for this purpose. Investigators may not withdraw data and biomaterials already deposited in the NIDA Center for Genetic Studies and the PI would continue to have access to their data.

The Role of the NIDA Genetics Steering Committee

The NIDA Genetics Steering Committee comprises extramural staff from various divisions and offices within NIDA and other NIH Institutes co-funding human molecular genetics research on substance abuse. The Steering Committee coordinates meetings and agenda of the NIDA Genetics Consortium (see above) and is actively involved in working with program staff in developing procedures and policies directly related to issues concerning human genetics research at NIDA. The Committee's other major function is to coordinate the review and approval of data sharing plans with program staff responsible for applications and principal investigators conducting human molecular genetics research.