Alcoholism, genes, and genetic background
PNAS has a new study out on the “modest” association between GABRA2 and “alcohol dependence.” The odds ratios pretty weak. But what struck me is that the populations they looked at was mostly European and African American. I wonder why these research programs just don’t focus on Native Ameicans; who are operationally an admixed population (European + Native American) and manifest a lot of alcohol dependence.
Citation: Laura J. Bierut, Arpana Agrawal, Kathleen K. Bucholz, Kimberly F. Doheny, Cathy Laurie, Elizabeth Pugh, Sherri Fisher, Louis Fox, William Howells, Sarah Bertelsen, Anthony L. Hinrichs, Laura Almasy, Naomi Breslau, Robert C. Culverhouse, Danielle M. Dick, Howard J. Edenberg, Tatiana Foroud, Richard A. Grucza, Dorothy Hatsukami, Victor Hesselbrock, Eric O. Johnson, John Kramer, Robert F. Krueger, Samuel Kuperman, Michael Lynskey, Karl Mann, Rosalind J. Neuman, Markus M. Nöthen, John I. Nurnberger, Jr., Bernice Porjesz, Monika Ridinger, Nancy L. Saccone, Scott F. Saccone, Marc A. Schuckit, Jay A. Tischfield, Jen C. Wang, Marcella Rietschel, Alison M. Goate, John P. Rice, and as part of the Gene, Environment Association Studies (GENEVA) Consortium, A genome-wide association study of alcohol dependence , doi:10.1073/pnas.0911109107
Studying genetics with Native American populations is extremely sensitive and so is the whole alcohol issue. Taken together, those working on such projects are well-advised to keep a low profile. It might take a Native American researcher to safely investigate.
Prairie Mary
This same group headed by Professor Beirut (I think they are mostly based at WashU) previously claimed that a SNP in the CHRM2 gene was associated with alcoholism and drug addiction, however the allele that they claimed was protective against alcoholism is actually at a very high allele frequency in Native Americans! (per the SNP chip Native American SNP allele frequency data collected by the PSU molecular anthropologist Mark Shriver).
I think 90% (probably more) of reported gene allele associations in the mental health literature are BOGUS and can not be replicated upon further investigation. It is a very sad state of affairs. For example three studies claimed that a SNP haplotype in the 3′ end of the CHRM2 gene was significantly associated with IQ. Then last year two large studies (Penelope Lind et al in Behav Genet and a meeting report study by McGue lab at U Minn) showed that the association of CHRM2 with IQ could NOT be replicated. Another large study showed that the claimed link of CHRM2 with major depression could not be replicated. The same story with most other links (e.g. SNPs in the dysbindin/DTNBP1 gene have been linked to schizophrenia and IQ but some studies indicate that this too is all bogus).
In my view the weakest link in the whole chain of evidence relating to the HBD paradigm is the distressingly shaky scientific evidence regarding the actual molecular allelic associations of specific genes with IQ and other mental traits and mental diseases. Almost all of the claimed associations are very tenuous and often unreproducible.