Genetic Associations Between Determinants of Intelligence and Determinants of Longevity

There is a well known association between intelligence and life expectancy, part of a web of related correlations that include wealth, social status, networks of relationships, and education, among others. In the case of intelligence, there is the intriguing possibility that genetics plays a significant role in this statistical relationship with longevity, and effects on life span are not just the results of a greater capability to succeed in obtaining wealth, status, and a consequently better usage of medical technology, for example. This paper points out that some of the same genetic variants influence determinants of both intelligence and mortality:

Cognitive functioning is positively associated with greater longevity and less physical and psychiatric morbidity, and negatively associated with many quantitative disease risk factors and indices. Some specific associations between cognitive functions and health appear to arise because an illness has lowered prior levels of cognitive function. For others, the direction of causation appears to be the reverse: there are many examples of associations between lower cognitive functions in youth, even childhood, and higher risk of later mental and physical illness and earlier death. In some cases, it is not clear whether illness affects cognitive functioning or vice versa, or whether both are influenced by some common factors. Overall, the causes of these cognitive-health associations remain unknown and warrant further investigation. It is also well recognized that lower educational attainment is associated with adverse health outcomes, and educational attainment has been used as a successful proxy for cognitive ability in genetic research.

The associations between cognitive and health and illness variables may, in part, reflect shared genetic influences. Cognitive functions show moderate heritability, and so do many physical and mental illnesses and health-associated measures. Therefore, researchers have begun to examine pleiotropy between scores on tests of cognitive ability and health-related variables. Pleiotropy is the overlap between the genetic architecture of two or more traits, perhaps owing to a variety of shared causal pathways. Originally, the possibility of pleiotropy in cognitive-health associations was tested using family- and twin-based designs. However, now data from single-nucleotide polymorphism (SNP) genotyping can assess pleiotropy, opening the possibility for larger-scale, population-generalizable studies. We aimed to discover whether cognitive functioning is associated with many physical and mental health and health-related measurements, in part, because of their shared genetic aetiology using the recently released UK Biobank genetic data. We curated genome-wide association study meta-analyses for 24 health-related measures, and used them in two complementary methods to test for cognitive-health pleiotropy.

Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

Link: http://dx.doi.org/10.1038/MP.2015.225

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