Exploring the behavioral genetics of Trade and Cooperation

1. Exploring the behavioral genetics of Trade and Cooperation Arcadi Navarro and Elodie Gazave July 5th 2007

2. Many lines of evidence a relationship between human social behavior and genetic variability • Different levels of various hormones have been correlated with different behaviours. (Testosterone, Harris 1999, Jiang & Huhtaniemi 2004; serotonin, Rot et al. 2006; Zaboli et al. 2006; oxytocin, Kosfeld et al. 2005). • The study of twins suggests a significant role of genetic factors in human cooperative behaviour (e.g., Rushton 2004; Brendgen et al. 2005). • Genetic variants have been linked to many personality disorders, from autism to suicidal behavior or drug addiction (Van Belzen & Heutink 2006; Van den Bogaert et al. 2006; Zaboli et al. 2006). • Behavioral diversity of genetic origin must have been crucial in the evolution of human-specific cooperation. • Not to mention new research on animal social behavior, which is uncovering strong genetic components. All this suggests that behavioral traits are analogous to other complex traits

3. Heritability studies (mostly twin-based) show that genetic variability for behavioral traits is considerable A few examples of the heritability levels of behavioral traits

4. Indeed, heritability of behavioral traits is not different from that of other traits and diseases that have been under genetic study for decades • Classical twin analysis. Percentage of variances explained by: • - Genetic factors (purple), • - Shared environmental factors (green), • - Unique environmental influences (beige) • - Differences in age (blue).

5. Consider, for example, Rheumatoid Arthritis, with its 60% heritability

6. Risk factors have been identified (and confirmed) in many association studies Key: bipolar disorder (BD) coronary artery disease (CAD) Crohn’s disease (CD) hypertension (HT) rheumatoid arthritis (RA) type 1 diabetes (T1D) type 2 diabetes (T2D)

7. And new genetic factors are being unveiled over the last few months in the largest association studies ever (e.g. WTCCC)

8. Interestingly, these genetic factors correspond to many different forms of functional genetic variation Sequence • Single base-pair changes – point mutations (SNPs, Single Nucleotide Polymorphisms: 3Mb diff between any two genomes) • Small insertions/deletions– frameshift, microsatellite, minisatellite • Mobile elements—retroelement insertions (300bp -10 kb in size) • Large-scale genomic variation (>10 kb) • Large-scale Deletions and Amplifications • Segmental Duplications / Copy Number Variation (CNVs, Up to 15Mb diff. between any two genomes) • Chromosomal variation—translocations, inversions, fusions. Cytogenetics

9. An example of Copy Number Variation (Eg. 5q13) Schmutz et al., (2004) Nature. 431:268-271

10. So we intend to conduct an association study on behavioral scores related to cooperation and trade. • What will we do? • Use well defined and easy to measure traits. • Collect DNA with mouth swabs. • Association study with an Array of >100k SNPs. • Parameter estimates and in-silico functional analysis of candidate causal genes or genomic regions. • Why? • A usual problem in classical studies. (Even in disease studies, diagnosis as a source of non-replication). • They are simple, trusty and increasingly used. • Large and avoid use of relatives. Array allows to study many forms of variation. • The way forward after associated markers have been detected.

11. So we intend to conduct an association study on behavioral scores related to cooperation and trade. • What will we do? • Use well defined and consistent traits. • Collect DNA with mouth swabs. • Association study with an Array of >100k SNPs. • Parameter estimates and in-silico functional analysis of candidate causal genes or genomic regions. • What will we get? • Cooperative traits scored in ~600 individuals. • Enough DNA from every one of these individuals. • Sets of many different variants (SNPs and CNVs) associated to different scores. • Lists of functional genomic elements (genes, miRNAs…) related to scores. Overview of the genetic architecture of cooperation and Trade.

12. 1. Use well defined and consistent traits Cooperation-related traits will be scored in individuals during different social/economic games. Individuals will be subject to different rounds of games to check for consistency. Initially, we will consider two games: - Ultimatum Game (as in Wallace et al., submitted) - Investments Game (as in Kostfeld et al. 2005)

13. 2. Collect DNA with mouth swabs. After informed consent signature, DNA will be extracted with mouth swabs and shipped to the lab.

14. 3. Association study with a >100k array. Standard SNP association studies will be performed with a >100K SNP Array. • Frequent • Well distributed • Stable • Perhaps functional • Easy to process

15. 3. Association study with a >100k array. Different genotyping technologies are available… Illumina SNPlex Sequenom TaqMan 1500 - 300 SNPs 400 - 40 SNPs 40 - 5 SNPs 10 - 1 SNPs

16. 3. Association study with a >100k array. Test DNA 1 Test DNA 2 … but we will focus on the ones allowing for Whole Genome Scans Illumina: ~300k array of (old) tagSNPs. ~500k tagSNP array now available. Affymetrix: ~500k evenly-spaced SNP array. A ~1000k array already available. Plus many custom arrays: for inflamatory pathways, imnune pathways and so on.... SNP Arrays work by comparative Intensity Analysis

17. 4. Parameter estimates and functional. • We will tackle questions such as… • What are the involved functional elements? • Where are they expressed? • In which pathways do they play a role? • How is extant human variability around these regions? • How have they diverged from other primates? • Any molecular signatures of recent or ancestral natural selection? • … and many others.