Written by: Stephen Hsu
Primary Source: Information Processing
CNVs (structural genomic variants) associated with increased autism and schizo risk are found to depress cognitive function in carriers who do not present for either condition. There are also effects on physical brain structure.
This is the future of neuroscience: read out the genome and look for the direct effect on phenotype. Assuming the results hold up, we can conclude that these mutations cause abnormal cognitive function in humans. We are just at the beginning of this line of research: mutations of smaller effect size will require larger samples to detect, but they almost certainly exist.
Note this is deCODE and Kari Stefansson — they have access to all health records and genotypes in Iceland. See also deCODE, de novo mutations, and autism risk.
In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
This figure shows impairment in population SDs for different groups. V IQ and P IQ are Verbal and Performance IQ (Wechsler), IIUC.
From the Supplement — check out the p values ;-)
My guess is that most intelligence alleles have negative effect. That is, the majority of genetic variation in cognitive ability is determined by the number and type of somewhat deleterious mutations we all carry around. (There are probably also minor alleles of positive effect, but fewer of them.) Note the CNVs in this article, while having a significantly (1 SD) negative effect on IQ, do not prevent reproduction (fecundity is reduced, but not to zero), so clearly mutations of large effect can linger for some generations. Mutations of smaller effect might even be neutral due to pleiotropy, etc.
Latest posts by Stephen Hsu (see all)
- Precision Genomic Medicine and the UK - February 15, 2019
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- Genomic Prediction of Complex Disease Risk (bioRxiv) - January 8, 2019