DUF1220 copy number is linearly associated with total IQ



From: Volkmar Weiss [mailto:Volkmar-Weiss@t-online.de]
Sent: Mittwoch, 21.
Januar 2015 10:59
To: 'James.Sikela@ucdenver.edu'
Subject: DUF1120 copy number is linearly associated with IQ

Dear Professor Sikela:

Yesterday  I read in Human Genetics 134 (2015) 67-75  the full text of your publication on „DUF1220 copy number is linearly associated with increased cognitive function as measured by total IQ and mathematical aptitude scores”,

see http://www.ncbi.nlm.nih.gov/pubmed/25287832 ,

full text: https://drive.google.com/file/d/0B3c4TxciNeJZcHg4ek9nWDZGcWs/view?pli=1

As I did catch sight of your Fig. 2 on page 72 I got deeply impressed, deeply moved, deeply: A linear association between copy arrayCGH based CON2 copy ratio versus WISC IQ, extending in the IQ range between 80 and 140. This is a breakthrough, a centennial breakthrough! My congratulation to your lab and the cooperating colleagues in New Zealand!

We are aware: What you have discovered is the tip of an iceberg. But it is the tip!

Your were even clever enough to obtain a patent for the determination of IQ by this copy number variation (CPV),

see http://www.google.com/patents/WO2014028768A2?cl=en

DUF means a protein “domain of  unknown function“, containing a number of genes, especially of the NBPF family, each of it highly polymorphic. 

 We need and this research may already under way in your lab:

1.      Family studies of the inheritance of CON2 copy ratio and IQ. There all  over the world thousands of families with more than one gifted in the IQ range around 130, ready to be  probands.

2.      Representative population data.

Until now it was assumed by the majority that IQ differences are caused by thousands of genetic polymorphisms each of it making a small contribution of plus or minus  1, 2  or even3  IQ points. Therefore the environment must play an important or decisive role. Since decades, whoever hinted that this thousand-genes-theory did not agree with the data of segregation of IQ within families, see for example http://www.v-weiss.de/majgenes.html  ,   was seen as an obstinate crank. However, in 1972, already in my  dissertation I wrote that the hypothetical major gene locus of general intelligence could turn out to be a series of alleles. And in 1992: “Of course, the allele M2 could also be understood as an abstraction and be in reality a series of n alleles with small differences; but with a large difference to the M1 allele or an allele-1 series.”  

The difference between the means of the hypothetical  M1M1 and M2M2 is about 30 IQ points.  This is the range, what you found!  The other hundreds of polygenes which, of course,  influence mental power under certain circumstances may add up to IQ differences of 20 points in extreme and rare cases, but because  the  minor genes are  segregating  independently of each other, their effects as a sum are normally distributed making only a plus or minus of about 5 IQ-points in the general population.

As we know, in the search for major effects on IQ all  genome-wide association studies (GWAS)  were a failure. Therefore, the conclusion had to be drawn that the explanation had to be found in previously unexplored regions of the genome.

Therefore, since some years I suggest  to look for copy number variations and the application of homozygosity array mapping within families of the highly gifted. See my monograph “Die Intelligenz und ihre Feinde” (Intelligence and its Enemies). Graz 2012, page 236 to CPV: „Da es sehr gut vorstellbar ist, daß diese Art der genetischen Variabilität auch in der Genetik des normalen IQ eine wichtige Rolle spielt, konzentrieren sich die Hoffnungen gegenwärtig auf weitere Erforschung dieser ‚Copy number variations‘ (CPV).“

You and your lab had the knowledge. You did it. My congratulation.

I wish you the possibility, the freedom and the courage to extend your findings. You will need it.

(I will forward this email to colleagues all over the world. I am sure, they will forward this message further.  What is urgently  needed is deepening of your findings, before the enemies of freedom become aware of the importance of your discovery and are threatening and hampering .)

Sincerely yours

Volkmar Weiss

The mouse has 1 copy of DUF1220, monkeys about 40, chimpanzee 120, homo sapiens nearly 300, with high IQ about 8 more than with low IQ., see