Genius? Avoid rare functional genes

 

For some time now I have been waiting for the results of the genetic analysis of genius, even while knowing that intelligence is heritable, but created by many, many genes of small effect. So, needle, haystack, and the needles aren’t just for sewing, but do other things as well.

However, on the good side, I believe that Plomin will nail the genes for intelligence before they nail him. This paper brings us a step closer to understanding the genetic underpinnings of exceptionally high intelligence, suggesting it happens when some intelligence damaging genes are not present. The team have looked at only the subset of DNA that encodes proteins,  because mutations in those sequences are much more likely to have severe consequences.

https://kclpure.kcl.ac.uk/portal/robert.plomin.html

A GENOME-WIDE ANALYSIS OF PUTATIVE FUNCTIONAL AND EXONIC VARIATION ASSOCIATED WITH EXTREMELY HIGH INTELLIGENCE Robert Plomin1 , Sarah L. Spain2 , Inti Pedroso2 , Neli Kadeva2 , Mike B. Miller3 , William G. Iacono3 , Matt McGue3 , Evie Stergiakouli4 , George Davey Smith4 , Martha Putallaz5 , David Lubinski6 , Emma L. Meaburn7 , Michael A. Simpson2

1 Institute of Psychiatry, Psychology & Neuroscience; King’s College London, robert.plomin@kcl.ac.uk.

2 Division of Genetics and Molecular Medicine, King’s College London.

3 Department of Psychology University of Minnesota.

4 MRC Integrative Epidemiology Unit University of Bristol.

5 Duke University Talent Identifcation Program Duke University.

6 Department of Psychology and Human Development Vanderbilt University. 7 Department of Psychological Sciences Birkbeck, University of London.

Although individual differences in intelligence are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. The present study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations.

We performed a case-control association analysis with 1,409 individuals drawn from the top 0.0003 (IQ > 170) of the population distribution of intelligence and 3,253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina Human Exome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes.

However, analyses using genome-wide similarity between unrelated individuals (Genome-wide Complex Trait Analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (SE 0.017) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis.

A common theme emerging from genetic studies of intelligence, similar to all complex traits and common disorders, is its highly polygenic nature with its heritability explained by many variants of small effect. While the unique extreme sampling design used in the current study provides improved power to detect associations in certain situations it has also provided challenges for direct replication. Nevertheless, the evidence for the contribution of protein-altering variants to the heritability of intelligence and the evidence that rare functional alleles are detrimental to intelligence provides a framework for defining the role of individual rare alleles.