Ninety-nine genetic loci influencing general cognitive function

Written by: Stephen Hsu

Primary Source: Information Processing

The paper below has something like 200 authors from over 100 institutions worldwide.

Many people claimed just a few years ago (or more recently!) that results like this were impossible. Will they admit their mistake?

In Scientific Consensus on Cognitive Ability? I described the current consensus among experts as follows.

0. Intelligence is (at least crudely) measurable
1. Intelligence is highly heritable (much of the variance is determined by DNA)
2. Intelligence is highly polygenic (controlled by many genetic variants, each of small effect)
3. Intelligence is going to be deciphered at the molecular level, in the near future, by genomic studies with very large sample size

See figures below for a summary of progress over the last six years. Note 4% of total variance = 1/25 and sqrt(1/25) = 1/5, so a predictor built from these variants would correlate ~0.2 with actual cognitive ability. There is still much more variance to be discovered with larger samples, of course.

Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

General cognitive function is a prominent human trait associated with many important life outcomes including longevity. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360). We found 9,714 genome-wide significant SNPs in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.

The following two tabs change content below.
Stephen Hsu
Stephen Hsu is vice president for Research and Graduate Studies at Michigan State University. He also serves as scientific adviser to BGI (formerly Beijing Genomics Institute) and as a member of its Cognitive Genomics Lab. Hsu’s primary work has been in applications of quantum field theory, particularly to problems in quantum chromodynamics, dark energy, black holes, entropy bounds, and particle physics beyond the standard model. He has also made contributions to genomics and bioinformatics, the theory of modern finance, and in encryption and information security. Founder of two Silicon Valley companies—SafeWeb, a pioneer in SSL VPN (Secure Sockets Layer Virtual Private Networks) appliances, which was acquired by Symantec in 2003, and Robot Genius Inc., which developed anti-malware technologies—Hsu has given invited research seminars and colloquia at leading research universities and laboratories around the world.
Stephen Hsu

Latest posts by Stephen Hsu (see all)