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Scientists find gene interactions that make cocaine abuse death 8 times more likely
Date:1/22/2013

, we can ask whether such interactions do exist between variants that may be a normal variation in the population. These kinds of interactions may underlie the genetics of behavior."

These specific findings apply primarily to whites. The researchers found that a different combination of variants affect the risk of cocaine abuse death in African Americans, and that in this population, some of the variants had protective properties.

The research is published in the online journal Translational Psychiatry.

The mutations are mostly single-nucleotide polymorphisms, or SNPs (pronounced "snips"). Each gene contains two alternative forms called alleles that are functionally identical in most people. However, in some cases, the activity level, or expression, of an allele can differ from its partner allele in a single gene.

The SNPs described here are on two genes: the dopamine receptor D2, which is a target for antipsychotic drugs, and the dopamine transporter DAT, the main target of cocaine and amphetamines.

The variants' clinical relevance was determined in earlier work led by Sadee that analyzed human brain autopsy tissues of people who had died of cocaine overdose and from age-matched drug-free controls.

The variants identified in this work are harder to detect and analyze than many mutations because these variants have no role in making protein; they exist in deeper and often overlooked regions of genes. Sadee's lab has designed a technique to predict and determine their functions based on measurements of how much messenger RNA, a carrier of genetic information, each specific allele expresses.

Having a defined set of a manageable number of variables then made a statistical analysis both possible and a critical step to more fully understanding the effects of these variants. First author Danielle Sullivan, a doctoral student in biostatistics at Ohio State, built logistic regression models to search
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Contact: Wolfgang Sadee
Wolfgang.Sadee@osumc.edu
614-292-1597
Ohio State University
Source:Eurekalert

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