Genetics of Cognition

Authored by Sumeet Sharma • 
August 22, 2016

Today, the way that associations between genes and an outcome are made are through genome-wide association studies (GWAS). In this approach, variation in an individual's DNA is measured, along with information about the outcome being studied. In the case of GWAS for disease, the simplest set up is to ask whether a particular genetic variant is more associated with a group of diseased individuals, in comparison to a control group of non-diseased individuals. Regarding cognition, psychiatric disease is our best window into what genetic variants influence the way that healthy people think - simply because cognitive domains relevant to disease are well-studied. More recently, companies like 23andMe have been able to collect DNA information from hundreds of thousands of individuals and have used this data to investigate genetic variants that influence normal variation in cognitive processes, such as being a morning person.

Below I catalog some of the domains of normal cognition into which GWAS can give insight. The main limitations of these studies are the specificity of the outcome measures and the number of individuals for which gene sequence information is available. Many of these genetic variants I discuss below are preliminary because more studies, and larger studies, are needed before the association between a genetic variant, and an outcome can be confirmed. However, insights gained from these investigations shine a light into how your genes can influence your everyday behavior.

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| Gene symbol | Gene Name | |:------------|----------------------------------------------------------------------| | GSK3B | glycogen synthase kinase 3 beta | | FYN | FYN oncogene | | ROBO2 | roundabout, axon guidance receptor, homolog 2 | | SEMA3A | sema domain, immunoglobulin domain 3A | | SEMA4B | sema domain, immunoglobulin domain 4B | | GABRB1 | gamma-aminobutyric acid (GABA) A receptor, beta 1 | | PTGDR | prostaglandin D2 receptor (DP) | | GLRA3 | glycine receptor, alpha 3 | | LEPR | leptin receptor | | PRSS2 | protease, serine, 2 (trypsin 2) | | FGF14 | fibroblast growth factor 14 | | RAPGEF2 | Rap guanine nucleotide exchange factor (GEF) 2 | | CACNB2 | calcium channel, voltage-dependent, beta 2 subunit | | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 | | PLA2G4E | phospholipase A2, group IVE | | HTR3E | 5-hydroxytryptamine (serotonin) receptor 3E, ionotropic | | KCNQ4 | potassium voltage-gated channel, KQT-like subfamily, member 4 | | JMJD2C | lysine (K)-specific demethylase 4C |

How can we operationalize genetic information?

From a personal perspective, the idea of genetics playing a large role in cognition may seem disheartening. It may appear that your genetics determine your destiny. However, we have to emphasize that these are only associations. Having a variant associated with an increased profile of aggression does not mean that you will pick fights wherever you go. Indeed, it may be that you have other genetic variants that offset the effects of the first. At the moment, we simply don't have the statistical power or enough individuals with their genes sequenced to make sense of the immense amount of variation in the human genome.

So the take home message is this, understanding more about your biology can only help to inform you. For instance, if you are strongly pre-disposed to be a morning person, you can optimize your daily routine so that you aim to accomplish more complex tasks earlier in the day, and save more routine work for later in the day. If you are not a morning person, you can do the opposite. Simply knowing what your biases are, can help you to perform at your maximum, and take advantage of, or assuage your predispositions. In the following section, we briefly cover some of the best-understood domains of cognition and keep in mind that even these domains are not fully understood. This page is a work in progress, and we will continue to explore the genetics that underpin well-understood domains of cognitions.

Aggressiveness

Evolutionarily, aggressive behavior has assisted human ancestors in competitions for food, mating rituals, defense from predators and other resource-limited scenarios. However, as humanity has become more a social, interdependent, and peaceful community many of these traits are detrimental. Aggressiveness is categorized as proactive and reactive. Proactive aggression is deliberate and preplanned and thought to be related to reduced emotional sensitivity. Reactive aggression meanwhile is related to increased emotional sensitivity and is mediated by a heightened sensitivity to perceived threat.1

Here is a table of some of the genes implicated in genome-wide association studies of anger and aggression.1

Impulsivity

Impulsivity is widely studied because of its close association with many psychiatric disorders. However, impulsivity is multi-faceted, and in some contexts may be advantageous, when rapid action is required. Several genes are implicated in impulsive behavior.2

Morning person

Recently, 23andMe used the aggregate data from its customers to discover genes that are associated with "being a morning person." 23andMe determined from two questionnaires (asking "Are you naturally a night person or a morning person?") which people preferred and then used the genetic information they had gathered to identify genetic variants that associated more with being a morning person.3

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