AB146. CD38 gene expression and social phenotypes: blood genomics as a proxy for CNS function.

Abstract

Given the moderate heritability of most complex traits, in which environment plays an important role, the sole pursuit of genetic markers alone may fail to reveal the fullness of phenotypic variance. A complimentary approach is to measure biomarkers in accessible tissues such as blood. Gene expression, which reflects both hereditable and environmental influence, is a particularly attractive focus of investigation Measurement of mRNA levels is likely to capture more of the phenotypic variance, both genomic and epigenetic than a unitary gene based approach. Most importantly, expression levels of many genes show good correspondence between peripheral blood and brain. These considerations have catalyzed an increasing number of investigations demonstrating a relationship between peripheral transcription of both specific candidate genes as well as whole genome expression and many behavioral syndromes. Indeed, so-called ‘blood genomics’ is becoming an important tool in dissecting complex behaviors. However, no studies to our knowledge have yet leveraged blood genomics towards understanding social decision-making. In a large ongoing study of risk and social decision-making in Singapore and China the B2ESS group has genotyped (GWAS) more than 3,000 Han Chinese subjects. In a subsample of subjects gene expression was measured in peripheral blood. We find an intriguing association between CD38 gene expression in blood and a number of social phenotypes including scores on Baron-Cohen’s autism quotient questionnaire (N=192, P=0.002, coef =3.933), TCI novelty seeking (N=187, P=0.004, coef =−7.186) and scores on the Hope questionnaire (N=228, P=0.048, coef =0.905). CD38 gene activity is also correlated with proposer’s offer in ultimatum game, but only in males (N=120, P=0.018, coef =2.797). These findings suggest that blood genomics can be a complementary approach to understanding the role of CD38 in human social behavior.