Aversion to Cilantro? Please...

Here is a study claiming to find a link between some gene and not liking cilantro.  The fact that this is obviously going to be another study that finds a false positive and tries to sell it as a big new finding is inevitable.  Here is the tipoff before even looking at the study:

Eriksson says that nearly half of all Europeans have two copies of this variant, and of those people, 15 percent reported a soapy taste. In contrast, 13 percent of Europeans had no copies, and 11.5 percent of this group said cilantro tasted like soap.

If someone wants to defend this study, particularly the authors, I will actually go through the study and mock it specifically, but otherwise I don't think it is even worth debunking.  Clearly, Nature Journal has no sense of quality control.   They will print any study making any absurd claim.

Plomin & Craig, 2001: The genetics of intelligence (g) - Takin' it to the Brits

This was one of my favorite letters to write.  I was passing some time in the "library" at my job and there happened to be a British Journal of Psychiatry sitting on the table.  I pick it up and, lo and behold, there is a study purporting to show a genetic link for g (a fanciful version of I.Q).  I'm sure the authors didn't intend it, but this kind of stuff is really not much different than old time eugenics.  I decided to challenge the assertions and sent the BJP a letter.  To my surprise, they printed it with a reply from the authors.  I was quite amused that they changed my "randomization" to "randomisation" for the Brit-friendly audience.  I also didn't know that they call raisins "sultanas" there.  Rather than post the letter and the reply from the authors (which is linked above), I'll just make a few points:

Ten Years Later: Where's the Beef? My letter to AJP RE: Stephen V. Faraone, Ph.D., et al. claim that D4 receptor linked to ADHD using Meta-analysis as proof...

I can be a mean bugger sometimes.  I read some of my old letters and I think, “Am I still that angry?”  I wish I could say no.   In any case, this letter  of mine from 2002 was published by the American Journal of Psychiatry along with  a reply; a reasonably polite one, I must admit, when I compare it to my original in retrospect.  In it, they seemed to suggest that my point wasn’t clear on a couple of occasions. I was happy enough that the American Journal of Psychiatry printed my abrasive and contrary letter, but now that any fool can have his own personal blog, I will see if I can make it clearer.  Here I will print their response and explain my case:

1.We agree that meta-analysis can be misinterpreted if an original positive finding is included. Dr. Pittelli overlooked our Table 3, which showed that the meta-analysis was significant when this study was exclude. 

2. There is no statistical basis for Dr. Pittelli’s assertion that a meta-analysis is biased if it includes a study from the person who performed the meta-analysis. He also overlooked Table 4, which showed that the meta-analysis was significant after omission of our study. Dr. Pittelli claims that research presented at national conferences or solicited from the ADHD Molecular Genetics Network e-mail list is biased; this is incorrect. The main bias of concern to meta-analysis is that negative studies are published, not that conference reports are more positive than published studies. Dr. Pittelli asks why we think it unfortunate that studies of ADHD and the D₄ receptor gene have not consistently confirmed their association. It is unfortunate because the use of small study groups to detect small effects obscures findings and inhibits progress.
3. The claim that a meta-analysis of studies of ADHD and the D₄ receptor gene must include all other genes tested makes no sense. Studies of different genes test different hypotheses. Mixing apples and oranges does not clarify any statistical analysis.
4. Dr. Pittelli incorrectly claims that whether ADHD genes truly exist remains an unproven assumption. The twin literature about ADHD clearly indicates that ADHD is one of the most heritable of psychiatric disorders (1). Moreover, the genetics literature is consistent with a multigenic theory of ADHD (2), despite Dr. Pittelli’s claim that such a theory is circular.We never claimed that our meta-analysis proved the D₄ receptor gene to be a susceptibility gene for ADHD. We concluded that the extant data were strong enough to warrant further studies of the D₄ receptor gene and ADHD.

Alright, I will try to answer all their points by giving a hypothetical meta-analysis below the fold:

My Strategy For the Short Term

As noted in the subheading above, I have been interested in the lack of solid genetic evidence for mental illness, particularly schizophrenia, for 25 years and I have written several letters to psychiatric journals challenging these studies.  The past few years, I have been busy doing other things, but now I have created this blog to devote an entire website to challenging the studies that claim to show such links.  The question is just how far back and how many studies do I need to challenge?  Hundreds of genetic linkage studies have been performed, all claiming some gene or genetic loci is linked to a disorder.  None of these studies have been replicated and most are eventually, directly or indirectly, refuted by the studies that come after them.  I have already looked at two studies from the past two years. 

There were  three landmark studies from 2009 in Nature, that got the media fairly excited, with the usual “Genes found for Schizophrenia” inaccuracies.  The meager findings of these studies have already been discussed by others.  However, I think it is worth analyzing even the weak claims made by those studies, so my plan is to refute  these studies over the next couple of weeks, to eliminate even the meager claims made.  At that point, I feel we are at close to point ZERO, where I can legitimately claim that there are no valid, replicable studies showing any specific genetic link for schizophrenia to date.  That way, I can then address only the new studies to come out.  I intend to bury this waste of time, money and misinformation under the scrap heap of bad science.  Good riddance!

My Critique of: NATURE GENETICS - Genome-wide association study identifies five new schizophrenia loci, Stephan Ripke et al

If I was even willing to accept this study on its face, this is my “shorter” interpretation of its conclusion:

“We did a mega-analysis of 17 genetic loci genome scan studies for schizophrenia.  We found 7 genetic loci correlating to schizophrenia.  Of those, 5 were NOT FOUND IN ANY OF THE ORIGINAL 17 STUDIES, NOR IN ANY PREVIOUS STUDY.  The remaining 2 were found in SOME of the studies.  Thus, any correlations other than those two found in any of the studies have been effectively negated. “

Thus, even if you accept the study, the conclusion seems to point to the fact that almost all of the findings in the studies it analyzes were, in fact, statistical artifacts.  Interesting.  It's more interesting that the authors did not  seem to be aware of this fact, or didn't think it was pertinent. 
Moreover, like many meta-analyses (or mega-analyses at the case may be) the study itself uses some rather complicated statistical analysis that I think is already questionable, and I discuss that briefly below the fold.  It will cost you $32 to check out the full study for yourself.  I paid it so you don't have to...

My First Critique of a Study for this Blog: Talkowski et al, Cell Magazine, "Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries"

I wrote a letter criticizing this study from Cell Magazine. Receiving no response, I wrote a follow-up letter to that letter. That was several months ago. To date, I have not received a response. I will therefore present my criticisms here. If you have a scientific or medical background and you would like to respond to my criticism, I will be happy to carry on a dialog through the comment section: This study generated a number of media articles further promoting the misconception that there have been genes or genetic loci that have been definitively linked to various mental disorders. Note a headline related to this study:

  Researchers discover new genes contributing to autism, links to psychiatric disorders 

 Now, is that really what the researchers discovered? Let's take a closer look. Here's what they found:

Screening the genomes of 38 individuals diagnosed with autism or other neurodevelopmental disorders found chromosomal breakpoints and rearrangements in non-protein-coding regions that disrupted 33 genes, only 11 of which previously had been suspected in these disorders. 

 So we have a "screening" study and 22 of the 33 genes were noted for the first time and the other 11 had been "suspected." The idea of a screening study is to find possible genetic links to examine in future confirmational studies. You should do the follow-up study before making specific claims. Yet the author is quoted as follows:

"The theory that schizophrenia is a neurodevelopmental disorder has long been hypothesized, but we are just now beginning to uncover specific portions of the genetic underpinnings that may support that theory," says Talkowski. "We also found that different gene variations -- deletion, duplication or inactivation -- can result in very similar effects, while two similar changes at the same site might have very different neurodevelopmental manifestations. We suspected that the genetic causes of autism and other neurodevelopmental abnormalities are complex and likely to involve many genes, and our data support this."

 Well, your data doesn't really support this, Dr. Talkowski. It only supports it if you were to ignore the possibility of false positives and the genes you found are actually directly related to the diagnoses in question. In this case, the researchers focus on a subgroup of patients with autism and “abnormal chromosomes,” which is not typical or classical autism and already brings the research into question when extrapolating it to those without genetic abnormalities and is additionally compounded by including schizophrenia despite no obvious chromosomal abnormalities in most individuals diagnosed with schizophrenia. There is some question as to whether such cases are even looking at the same thing as classical autism and schizophrenia in individuals without chromosomal abnormalities. Furthermore, no control is used looking at a similar group of individuals with chromosomal abnormalities without autism to see if they also have similar DNA disruptions. Actually, a second and third control should also be used to determine how many individuals with autism and no structural chromosomal abnormalities have such DNA disruptions as well as a group of non-autistic individuals without chromosomal abnormalities (“normals”) with such DNA disruptions. It is not enough to just claim that such disruptions are “known to be significantly more common in autism and autism spectrum disorders.” The fact that such disruptions may or may not be more common might, in fact, be a red herring and have nothing to do with the disorder itself. Such controls should be done in any of these experiments and the lack of such controls make the data impossible to analyze as anything more than random. I would venture to guess that that is, in fact the case. I would also point out to the authors that, to date, there has not been a single consistently replicated study showing a gene, genetic loci or DNA disruption (etc.) for schizophrenia. Thus, for your group to find a “significant number” of such genes is interesting and surprising, to say the least. Let me suggest that a less interesting, but more realistic headline for the results of the study would be this:

Researchers do a genetic screening that may be worthwhile for future confirmational studies.