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NIDA

Collaborative Opportunities in Genetics Research

Revised May 2012

Consortium of adolescent studies for the genetics of smoking and nicotine dependence

We are interested in organizing a consortium of adolescent and young adult studies (up to age 24) to carry out a meta-analysis of genetic factors for nicotine dependence and extensive smoking in adolescence. We are aware of several adolescent studies that have genetic and phenotypic data. However, each study is underpowered for genetic analysis. Were we able to accumulate a large enough number of such studies, we might be able to implement a meta-analysis similar to that carried out for adults by Saccone and her collaborators (PLoS Genetics, August 2010) or Ware et al. (SRNT, February 2011).

We are particularly interested in longitudinal studies, but would also include cross-sectional studies. If your sample includes adolescents and DNA (whether or not yet extracted and /or genotyped), and you would be interested in a collaboration, please contact Denise Kandel at dbk2@columbia.edu, tel: 212-304-7080.

We have prepared a short survey to obtain some preliminary information about each study. We will ask you to fill out the questionnaire and return it to us. Our goal is to synthesize the responses to get an idea of how many studies would be available and of the ethnic-specific sample sizes. I will then get back to you to discuss the next steps. Under any event, for the meta analysis you will not be asked to provide the raw data but only the statistical coefficients from an agreed upon data analytical plan.

Meta-analysis of a functional variant in OPRM1 across multiple substance addictions invites additional collaborators for meta-analysis of rs1799971.

This collaborative meta-analysis targets multiple substance dependence diagnoses: alcohol dependence measured by DSM-IV, opiate dependence measured by DSM-IV, marijuana dependence measured by DSM-IV, cocaine dependence measured by DSM-IV, and nicotine dependence measured by FTND, including samples from multiple origins of ancestries (e.g. European, African, Asian, Hispanic). The primary goal is to assess the effect of the non-synonymous OPRM1 SNP rs1799971 (Asn40Asp, A118G) in case-control analyses across independent datasets which have measured one or more of these addictions. Family samples may be included by extracting unrelateds or by using mixed models.

We will centrally develop analysis scripts and distribute to each site. Meta-analyses will be carried out centrally using summary results from collaborating sites. As of February 2011, we have 21 groups and are in process of collecting basic sample distribution information. If interested, please contact Nancy Saccone.

Gene Environment Meta-Analysis of Nicotine Dependence (GEMINI)

Multiple genome-wide association studies suggest a link between variants in nicotinic receptor genes and nicotine dependence. To investigate the relationship of environmental factors to these reported genetic associations, we are performing a large meta-analysis of data from the Gene-Environment Meta-Analysis of Nicotine Dependence (GEMINI) Consortium to assess the environmental modification of genetic effects in several regions associated with nicotine dependence. Environmental factors evaluated include birth cohort, socioeconomic status, age of smoking onset, and education. By using a large sample size and focusing specifically on regions previously associated with nicotine dependence, we had adequate power to detect variation in the relationship between nicotinic receptor genes and nicotine dependence by environmental conditions.

Inclusion criteria: ever-smokers age >= 25 of European descent genotyped at rs16969968 or rs1051730.

We are interested in including all datasets that meet inclusion criteria, however, we are finalizing the analysis so participation must occur in a timely mannor. If interested, please contact Sarah Hartz.

The Study of Tobacco in Minority Populations (STOMP) Genetics Consortium Seeks Additional Collaborators for meta-analyses of GWAS data for smoking behavior among African-Americans.

The Study of Tobacco in Minority Populations (STOMP) Genetics Consortium was formed in early 2010 and consists of multiple investigators from different studies interested in conducting meta-analyses of GWAS data for smoking behavior among African-Americans. As of November 2010, n=27,072 African-American participants with GWAS and smoking data are available for analyses. The sample size represents participants from the Women's Health Initiative, the CARe studies and multiple NCI breast and prostate cancer studies. We are investigating smoking initiation (ever vs. never and age at onset of smoking), smoking heaviness (CPD) and smoking cessation (former vs. current smokers); have devised a standard analytic plan; and ask that new studies upload summary results to the MIT/Broad Shared Space. The STOMP Genetics Consortium analysts will conduct the meta-analyses. The Study of Tobacco in Minority Populations (STOMP) Genetics are actively recruiting more studies. Investigators interested in collaborating should contact Stacey Petruzella for more information.

Cross Population Meta-Analysis of Smoking and Chromosome 15

This cross population meta-analysis consortium is to study smoking and the chromosome 15 region across different racial groups. Our groups include populations of European, African and Asian descent and the outcome phenotype is Cigarettes Per Day (CPD). There are 24 datasets of European (N=9,588), African (N=5,685), and Asian (N=6,889) descent for a total of 22,162 smokers. Our goal is to study the findings in non-European groups on smoking, and to leverage the differences between the different ethnic groups to refine regions of interest. The relative strength of the association varies by population, driven by differences in linkage disequilibrium and allele frequencies between populations. Inclusion Criteria: study samples with diverse ancestry, data on smoking and genotyping on chromosome 15. We are interested in including datasets that meet the inclusion criteria, however, the analyses are being finalized. If interested, please contact Li-Shiun Chen.

CHARGE (Cohorts for heart and aging research in genomic epidemiology)

The CHARGE Consortium is conducting a meta-analysis of GWAS data for smoking cessation among subjects of European ancestry. This effort includes several prospective cohort studies such as ARIC, CHS, Rotterdam, Framingham, and Nurses' Health Study which are used to conduct time to quit analyses AND includes cross-sectional studies that reconstruct when someone started and quit in the past. CHARGE welcomes new GWAS studies that have data on ages or dates of smoking initiation and cessation. A detailed analytical plan has been developed and analyses are underway. Please contact Henning Tiemeier if you are interested in joining.

PNAT (Pharmacogenetics of Nicotine Addiction Treatment)

The PNAT Consortium was formed in 2005 with funding from NIDA to identify the role of pharmacokinetic and pharmacodynamic gene variation in nicotine dependence phenotypes, with a focus on prospective smoking cessation and medication response. In addition to conducting a large multi-institutional prospective randomized pharmacogenetic trial of smoking cessation, PNAT is conducting meta-analyses of candidate gene variation and smoking cessation among treatment-seeking smokers enrolled in completed randomized clinical trials (RCTs) of smoking cessation pharmacotherapies. If you wish to contribute, please contact Rachel Tyndale and Caryn Lerman.

Alcohol consumption meta-analysis (GENEVA-NCI)

GENEVA and NCI will be collaborating on a meta-analysis of alcohol consumption among subjects of European American ancestry. This effort includes approximately 17,000 GENEVA subjects and 17,500 NCI subjects. Log-transformed drinks/week will be the primary phenotype of interest and additional dichotomous phenotypes of heavy vs light drinking may also be analyzed. We invite investigators to join this highly collaborative effort. Please contact Arpana Agrawal and Neal Freedman if you have questions or are interested in collaborating with us.

This page was last updated May 2012

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