Frequently Asked Questions About the NIDA Genetics Consortium and All Human Genetics Studies at NIDA.

Q1. What is the NIDA Genetics Consortium (NGC)?

A1. In September 1998, NIDA issued a Request For Applications (RFA) entitled "RFA DA-99-003: Genetics of Drug Addiction VulnerabilityÓ to identify human chromosomal regions containing genes that confer susceptibility to drug abuse and addiction and related behaviors. The principal investigators of the studies funded under this RFA formed the initial membership of the NGC, and other investigators have subsequently joined. The NGC investigators represent multiple institutions, use diverse approaches and study designs, and are required to meet twice yearly to discuss issues related to the collection and analyses of data from human genetic studies on drug addiction.

The overarching goals of the NGC are to identify genetic factors involved in drug addiction and addiction vulnerability, and to create a database on the human molecular genetics of drug addiction for sharing among members and the broader scientific community. Toward this end, NGC members collect anonymized data on family structure, age, sex, clinical status, and diagnoses, as well as blood samples from which DNA and cryopreserved lymphocytes are derived. These data, plus all data derived from genotyping and other genetic analyses of these clinical data and biomaterials, are stored in the NIDA Center for Genetic Studies (NCGS). To learn more about the NCGS, please see FAQs about the NCGS.

Q2. How can I find out what studies are participating in the NGC?

A2. Information about the investigators and studies of the NGC can be found at the NCGS website, which is maintained at Washington University (http://zork.wustl.edu/). Click on the NIDA icon, select public information, and then click on study information.

Q3. How are human molecular genetic studies of addiction defined?

A3. 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 humans.

Q4. Is NGC membership available to investigators doing other human genetic studies of drug addiction such as twin studies and adoption studies that are not aimed at identifying specific genetic factors?

A4. No. Only investigators conducting the human molecular genetics of drug addiction research are eligible for NGC membership. Such studies aim to identify gene variants and chromosomal regions associated with drug addiction and are collecting biomaterials containing DNA. 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.

Q5. Do the members of the NGC meet to discuss progress, scientific advancements, etc?

A5. Yes. Members of the NGC are required to meet twice a year to discuss issues related to the collection and analyses of data from human genetic studies on drug addiction. These meetings are also designed to facilitate collaborations among NGC investigators. Cost for travel to these meetings is to be included in the PI's grant award.

Q6. Are all principal investigators of NIDA-funded grants studying the human molecular genetics of addiction encouraged to join the NGC?

A6. Yes. Because of economies of scale and the need to facilitate sharing through the centralized resource, all principal investigators of NIDA-funded grants studying the human molecular genetics of drug addiction are encouraged to contribute to and use the resources of the NCGS. 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;
• Have aliquots of high quality DNA extracted from the cell lines;
• Have the opportunity to meet, on a regular basis, colleagues engaged in similar genetics studies, thereby facilitating information sharing, problem solving, and collaborations.

Q7. Does NIDA require membership in the NGC for all principal investigators of NIDA-funded grants studying the human molecular genetics of drug addiction?

A7. No. NIDA strongly encourages, but does not require, membership in the NGC for investigators principal investigators of NIDA-funded grants studying the human molecular genetics of drug addiction. Investigators who choose not to join the NGC, however, will have to use resources from their grant to meet NIH and NIDA's expectations for data sharing for human molecular genetic studies of addiction (see Q13).

Q8. What is the application process for becoming a member of the NGC?

A8. Effective Sept. 1, 2004, the process for acquiring membership is:

1. Submission of requests for membership. Written requests for membership will be received three times per year (April 1, August 1, and December 1) by the NGC Chair with a copy to your project officer:

   Joni L. Rutter, Ph.D.
   Chair, NIDA Genetic Data Access Request Committee
   NIH/NIDA
   Genetics and Molecular Neurobiology Research Branch
   Division of Neuroscience and Behavioral Research
   6001 Executive Blvd.
   Rm 5227, MSC 9555
   Bethesda, MD 20892-9555
   Rockville, Maryland 20852 (for courier/overnight mail service)
   Phone: 301-443-1887
   Fax: 301-594-6043
   E-Mail: jrutter@mail.nih.gov

2. Review of requests for membership. The NIDA access committee, an outside panel of experts who serve to review the applications and advise the NGC Steering Committee, will convene by phone conference to discuss the merit of each request in the context of the existing studies with the NGC. This committee does not replace or supersede the IRG. In the situation where NIDA is unable to provide membership or access to all requests at a given time, the Access Committee will advise the NGC Steering Committee on prioritization of the proposals.

   The merit of the request will be determined by:

   1. Purpose and scope of the funded grant (only NIDA-funded grants will be considered for membership)
   2. Written plan to contribute biomaterials and phenotypic data
   3. Data sharing agreement [see Q13-17 for additional information]
   4. Design of study
   5. Need for the study (overlap with other studies in the NGC)
   6. Likelihood of finding genetic loci
   7. Adequacy of power to detect the hypothesized effect(s)
   8. Operationalization of phenotype
   9. Operationalization of environmental risk factors
3. Notification of decision. Notification will be approximately two months after submission of the request.
4. Confirmation of acceptance of membership. Investigators whose request for membership has been approved must confirm acceptance of membership by sending a letter of acceptance to join the NGC, countersigned by the appropriate business official at the investigator's sponsoring institution, to the NGC secretary.
5. Submission of grant and site information. New members to the NGC must send a copy of their grant abstract and their site information to the NGC Secretary and to the NCGS (john@zork.wustl.edu).

Q9. Are data sharing plans expected for all human genetic studies of addiction funded by NIDA? (If I am not approved for membership, am I still required to comply to the sharing policies outlined in this FAQ)?

A9. 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. If membership is not approved, NIDA will help guide the investigator to other potential resources or ways in which compliance to NIDA sharing policies can be maintained.

Q10. What are the data covered under this sharing plan?

A10. Phenotypic assessments, genotypes, and all research resources including biologic material.

Q11. 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?

A11. 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.

Q12. Does the Initial Review Group or Study Section evaluate the proposed data sharing plan?

A12. Yes, 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 and the NIDA Genetics Consortium Steering Committee.

Q13. What is an appropriate data sharing plan for membership in the NGC?

A13. An appropriate data sharing plan includes all elements of the NGC Model Data Sharing Plan. *

NIDA GENETICS CONSORTIUM MODEL DATA SHARING PLAN

1. Whole blood samples from each subject will be sent to the NIDA Center for Genetic Studies (NCGS), which will extract DNA and plasma and cryopreserve the lymphocytes. If the lymphocyte cell count is low, the NCGS will attempt to create a cell line immediately.
2. The NCGS will distribute DNA and plasma only to the principal investigator until the materials are available for sharing. If the principal investigator pays for and receives a copy of a cell line, they 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 NCGS will be the responsibility of the principal investigator and at the principal investigator's expense.
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 and regular updates will be provided to the NCGS throughout the project.
5. Verified genotyping data will be submitted to the NCGS 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. A statement in the data sharing plan acknowledging that the PI has read and agrees to the term set forth in the FAQ documents.
8. A statement describing a timetable specifying when various elements of the database (e.g., diagnostic assessments or genetic data) and DNA will be available for distribution. In general, 18 months after the termination of the grant period, including extensions, or immediately upon first publication of the data, whichever comes first, the NCGS will distribute DNA and data to qualified investigators who have been approved by the NIDA Genetic Data Access Request Committee [insert link] and who have signed the Distribution Agreement.
9. The NCGS 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.
10. The PI will participate in NGC meetings, which are held 2 times per year. Cost for travel to the NGC is included in the PI's grant award.
11. Most services of the NCGS shall be free to investigators belonging to the NGC. Services include providing the mailers and tubes needed to ship the blood to the Repository. The NCGS 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. For information about the fee structure, see [insert link to NCGS].

• Minor modifications will be considered by your program official and the NGC Steering Committee [see NIDA genetics steering committee and Q24].

Q14. Do these expectations about the dissemination of data and biological materials apply to all applications studying molecular genetics of addiction in humans?

A14. Yes. These expectations about dissemination of data and biological materials apply to all NIDA-funded research on the molecular genetics of addiction in humans.

Q15. Does NIDA need to approve my consent form?

A15. Yes. NIDA requires that your consent form be approved prior to submitting it to the local IRB. To see a model consent form, see Model Consent PDF file (88 kb).

Q16. What are the important elements to include in my consent form and data sharing plan?

A16. See: Data Sharing Plan Checklist PDF file (76 kb).

Q17. What is NIDA's process for approval of data sharing plans and reviewing the consistency of informed consent with the data sharing plan and will this be part of the terms and conditions of the Notice of Grant Award?

A17. The process for approval of the data sharing plans and informed consents is separate from the process for requests for membership, but should be done in parallel to the membership request. 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 issuing a Notice of Grant Award for most cases. 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 mediate the review with the NIDA Genetics Steering Committee and 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.

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."

Q18. How will applicants be informed of NIDA's expectations of dissemination of data and biological materials (DNA)?

A18. This FAQ document about NIDA's policy concerning the dissemination of clinical data and biological materials (DNA) for human molecular genetics studies is available on the web at:
http://www.nida.nih.gov/about/organization/Genetics/GeneticsHome.html. As part of the Data Sharing Plan, the applicant shall include a statement indicating that they have read and agree to the terms in the FAQ documents. The applicant is encouraged to speak to their program official or a member of the NGC Steering Committee prior to submission of their application.

Q19. 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?

A19. Cheek swabs cannot be processed through the NCGS at this time. However, DNA from cheek swabs can be used, provided that sufficient amounts of DNA of the entire genome from each individual can be generated and made available to the scientific community at the expense of the investigator. Given that current cheek swab methods may not provide sufficient amounts of high quality DNA and because high throughput genotyping of cheek swab DNA is difficult, blood remains the preferred specimen.

Q20. Is NGC membership open to investigators funded by other NIH institutes or funding agencies?

A20. Yes, provided that the application is co-funded by NIDA.

Q21. May investigators apply for administrative or competitive supplements so they can join the NGC?

A21. 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 other purposes that would make joining the NGC possible.

Q22. Will progress on my grant be reviewed differently if I do or do not become a member of the NGC?

A22. No. Your NIDA Program Official will review and evaluate your scientific progress each year and will make recommendations for continued funding based solely on such scientific progress. Membership in the NGC will have no bearing on this evaluation process.

Q23. If I join the NGC may I decide to withdraw later?

A23. Yes. You may withdraw from the NGC after joining by making such a request when submitting your non-competing renewal (i.e., progress report). However, investigators may not withdraw data and biomaterials already deposited in the NCGS and will continue to have access to their data. Furthermore, 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 human molecular genetics of drug addiction are met. You should not expect that NIDA will provide supplemental funds for this purpose. You must submit a revised data sharing plan. Your revised data sharing plan must be consistent with NIH and NIDA's requirements for sharing clinical information and biomaterials (DNA).

Q24. What is the role of the NGC Steering Committee?

A24. The NGC Steering Committee comprises extramural staff from various divisions and offices within NIDA and other NIH Institutes that co-fund human molecular genetics research on drug addiction. The NGC Steering Committee coordinates meetings and agenda of the NGC (see above) and is actively involved in working with program staff in developing procedures and policies directly related to issues concerning human molecular genetics research at NIDA. The NGC Steering Committee's other major functions are to coordinate other NGC-related matters including requests for NGC membership (see above) and requests for access to data stored at the NCGS [insert link for FAQs about the NCGS]. The NGC Steering Committee reviews and facilitates the process of membership approval and access by ensuring that NIH and NIDA data sharing practices are met and that other application procedures have been completed.