Genetic Intelligence Report (GIP): Exploring Key SNPs for Intelligence with Example

Introduction​​

Intelligence is a complex and multifactorial trait, influenced by the interaction of many genes, each contributing in a small but significant way. Today, the study of Single Nucleotide Polymorphisms  (SNPs) has become a crucial tool in unraveling the genetic factors that contribute to intelligence. While the SNPs listed below are some of the most famous ones associated with intelligence, there are many others that need to be considered for a complete analysis.

The Genetic Intelligence Project (GIP) report is  currently the best option for assessing intelligence, as it separates all the major genes and variants from the most important studies. In addition to providing a detailed analysis of genes, the GIP provides a scientific rationale for a person’s behavior and intelligence. While individuals can try to search for these SNPs in their raw genetic test data at home, commercial tests often do not provide sufficient breadth. Imputation is required to estimate the complete genome sequence, something that the GIP provides comprehensively.

Updated List of SNPs and Effects

1. COMT (SNP rs4680 – Val158Met)
   1. Effect allele : G (Val) and A (Met)
   2. Effect : The G (Val) allele  is associated with greater dopamine degradation in the prefrontal cortex, resulting in lower performance on working memory tasks. However, the G allele  is also linked to greater resilience to stress, which may benefit emotional intelligence.
   3. Reference : Correa, MA et al . A genome-wide association study for extremely high intelligence.  Molecular Psychiatry, 2016. doi: 10.1038/mp.2017.121.

• ADAM12 (SNP rs4962322)
  • Effect allele : C and T
  • Effect : The C allele  has been identified in analyses of extremely high intelligence. It is involved in processes of neurogenesis and cellular development.
  • Reference : Zabaneh, D. et al . A genome-wide association study for extremely high intelligence.  Molecular Psychiatry, 2017. doi: 10.1038/mp.2017.121.
• CHRM2 (SNP rs8191992)
  • Effect allele : A and G
  • Effect : The CHRM2 gene  is related to cholinergic neurotransmission and cognitive functions such as learning and memory.
  • Reference : Cargill, M. et al . Characterization of single-nucleotide polymorphisms in coding regions of human genes.  Nature Genetics, 1999. doi: 10.1038/10290.
• BDNF (SNP rs6265 – Val66Met)
  • Effect allele : G (Val) and A (Met)
  • Effect : The Met allele  is related to lower cognitive efficiency, especially in tasks involving memory and cognitive flexibility.
  • Reference : Cargill, M. et al . Characterization of single-nucleotide polymorphisms in coding regions of human genes.  Nature Genetics, 1999. doi: 10.1038/10290.
• FNBP1L (SNP rs11136000)
  • Effect allele : C and T
  • Effect : The T allele  is associated with increased IQ and neuronal development.
  • Reference : Cargill, M. et al . Characterization of single-nucleotide polymorphisms in coding regions of human genes.  Nature Genetics, 1999. doi: 10.1038/10290.
• SLC6A4 (SNP rs25531)
  • Effect allele : C and T
  • Effect : This SNP affects the serotonin transporter, impacting emotional and cognitive responses.
  • Reference : Glatt , CE et al . Screening a large reference sample to identify very low frequency sequence variants.  Nature Genetics, 2001. doi: 10.1038/86948.
• SYN2 (SNP rs2292911)
  • Effect allele : T (candidate allele)
  • Effect : The SYN2 gene  is involved in synaptic development and may impact neural development.
  • Reference : Cavalleri, G. et al . Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types.  The Lancet Neurology, 2007. doi: 10.1016/S1474-4422(07)70247-8.
• KCNAB1 (SNP rs10791097)
  • Effect allele : G and T
  • Effect : Associated with potassium channel function, this gene may influence neural signaling and cognitive performance.
  • Reference : Cavalleri, G. et al . Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome.  The Lancet Neurology, 2007. doi: 10.1016/S1474-4422(07)70247-8.
• NEGR1 (SNP rs2883497)
  • Effect allele : G (candidate allele)
  • Effect : Associated with greater brain volume in cognitive areas.
  • Reference : Ng, M. et al . Implication of genetic variants near NEGR1 with obesity and type 2 diabetes in Chinese.  The Journal of Clinical Endocrinology and Metabolism, 2010. doi: 10.1210/jc.2009-2077.

1. FTO (SNP rs9939609)
   1. Effect allele : A and T
   2. Effect : Variant best known for its relationship with obesity, but may also influence cognition in some populations.
   3. Reference : Ng, M. et al . Implication of genetic variants near FTO.  The Journal of Clinical Endocrinology and Metabolism, 2010. doi: 10.1210/jc.2009-2077.
2. KLF13 (SNP rs1049434)
   1. Effect allele : C and T
   2. Effect : Regulator of gene expression in brain development, associated with IQ.
   3. Reference : Not available .
3. NCAN (SNP rs1064395)
   1. Effect allele : A and G
   2. Effect : Involved in synapse formation and myelination, impacting cognition.
   3. Reference : Not available .
4. DYX1C1 (SNP rs3743205)
   1. Effect allele : C and T
   2. Effect : Related to dyslexia and possibly general intelligence.
   3. Reference : Not available .
5. SNAP25 (SNP rs363050)
   1. Effect allele : C and T
   2. Effect : Related to working memory and attention.
   3. Reference : Not available .
6. CACNA1C (SNP rs1006737)
   1. Effect allele : A and G
   2. Effect : Encodes a calcium channel subunit, associated with psychiatric disorders and cognition.
   3. Reference : Not available .
7. FKBP5 (SNP rs1360780)
   1. Effect allele : C and T
   2. Effect : The T allele  is associated with increased vulnerability to stress and psychiatric disorders such as depression and PTSD.
   3. Reference : Hartmann et al., 2016 .

Conclusion​​

These SNPs are just one part of the genetic puzzle that influences intelligence. For a complete analysis, the Genetic Intelligence Project (GIP) offers a unique approach that compiles the most relevant genetic variants and performs an in –  depth analysis of why a person might have high intelligence and their behavioral tendencies. Intelligence is polygenic , meaning that multiple genes contribute to its development, and the GIP is designed to provide a holistic view based on the most recent and comprehensive studies available.

Case Study: Giftedness with an IQ Higher than 146 and Great Professional Achievements

Genetic Profiling and Analysis of SNPs Related to Intelligence

This case study explores a profoundly gifted individual with an IQ above 146  and great professional achievements . In addition, the individual demonstrates high emotional resilience  and control under pressure , without any diagnosis of double exceptionality. The objective is to evaluate the genetic profile of this individual  , identifying SNPs associated with intelligence and their effects, to understand how they influence his cognitive and emotional performance.

Polygenic Intelligence and Genetic – Environmental Interaction​​

Intelligence is a polygenic  trait , determined by the interaction of many genes, each with a small individual effect. Combined, these genes can create a genetic profile that favors above – average cognitive performance. In addition, environment, education, and life experiences play crucial roles in the development of intelligence. Below is a detailed analysis of the main SNPs involved in a person’s cognitive and emotional performance.

SNPs considered partially beneficial can  , when combined with other highly beneficial SNPs, amplify  intelligence by adjusting the balance between cognitive, emotional and physiological functions. These SNPs can serve as homeostatic regulators , preventing excesses such as brain overexcitement or emotional overload, maintaining optimal brain function under various conditions.

Furthermore, genetic interactions can occur  synergistically. This means that a SNP that is “partially beneficial” on its own may have an enhanced effect when combined with other beneficial SNPs. In other words, SNPs that positively influence working memory , for example, may compensate for potential impairments in emotional functions , or  vice versa.

Important Considerations​

1. The Homeostatic Role of Partially Beneficial SNPs : SNPs that are considered partially beneficial may be responsible for balancing  the impact of more potent SNPs. For example, CHRM2 (AT)  and ADAM12 (CA)  may have regulatory effects in areas such as memory  and emotional control , helping to prevent the brain from operating at extreme levels during times of high demand.
2. The Interplay of Cognitive and Emotional Genes : Intelligence  goes far beyond academic performance or IQ. Emotional intelligence, stress management, and resilience are critical elements of a person’s overall success. Thus, SNPs that influence emotional control, such as COMT ( GG) , are essential in helping to balance high cognitive performance with the ability to remain calm  and in control  in high-pressure situations.
3. The Role of SNPs Related to Early Development : Genetic factors linked to mode of delivery , breastfeeding , and early life  can significantly influence neural and cognitive development. Although these SNPs are not included in the main list, it is crucial to consider that  early environment  and genes related to childhood development  affect long-term brain performance.
4. Nurturing Genetic Precursors : SNPs that are partially beneficial can be enhanced  by other SNPs or environmental factors. For example, the ADAM12 (CA) genotype , linked to extreme intelligence, can be activated  or better expressed if adequately supported by additional SNPs or environmental factors, such as good nutrition or a stimulating upbringing.
5. SNPs Related to Child Development :
   Breastfeeding and delivery  may  influence how the brain develops, as they are associated with a number of factors that affect early brain formation and neural circuit development. Factors such as breastfeeding have a direct  impact on future cognitive and emotional health, and including these SNPs may provide a more complete picture.

Reassessment of the Genetic Profile

Let’s review the case study considering these new observations:

1. COMT (SNP rs4680 – Val158Met) = GG

• Effect : The G allele  provides emotional resilience and robust stress management, especially in high-pressure situations. Although  it can affect working memory, it provides an essential balance, allowing the individual to focus on creative and high-demand areas.
• Conclusion : Good for emotional control  and resilience .

2. ADAM12 (SNP rs4962322) = CA

• Effect : The C allele  is related to extremely high intelligence, while the A allele  provides homeostatic regulation, which prevents cognitive excesses, promoting a balance between cognitive  function and emotional control.
• Conclusion : Partially beneficial , acting as a balancer .

3. CHRM2 (SNP rs8191992) = AT

• Effect : The A allele  is associated with improved memory and learning, while the T allele  may function as a controller to avoid cognitive overload in situations of high mental demand.
• Conclusion : Partially beneficial , helping with homeostatic control .​​

4. BDNF (SNP rs6265 – Val66Met) = CC

• Effect : The C allele  promotes synaptic plasticity , essential for continuous learning and adaptation throughout life.
• Conclusion : Beneficial , crucial for cognitive flexibility .

5. FNBP1L (SNP rs11136000) = TT

• Effect : Associated with an increase in IQ and neuronal development.
• Conclusion : Ben is good for intelligence  .

6. SLC6A4 (SNP rs25531) = TT

• Effect : The T allele  improves mood regulation  and emotional control, promoting good mental health.
• Conclusion : Ben is good for  emotional balance .

7. KCNAB1 (SNP rs10791097) = GT

• Effect : The G allele  is associated with cognitive improvements, while the T allele  helps modulate cognitive function, preventing overeating.
• Conclusion : Partially beneficial , with a homeostatic role .​​

8. FTO (SNP rs9939609) = TT

• Effect : Linked to metabolism and weight control, with indirect impact on cognition and general health.
• Conclusion : Ben is fictional .​​

9. KLF13 (SNP rs1049434) = AT

• Effect : The A allele  helps in brain development, while the T  allele modulates to avoid overload of neuronal activities.
• Conclusion : Partially beneficial .​​​

10. NCAN (SNP rs1064395) = AG

• Effect : The A allele  is beneficial for synaptic formation, with partial control by the G  allele  to maintain balance.
• Conclusion : Partially beneficial .​​​

11. DYX1C1 (SNP rs3743205) = CC

• Effect : Related to intelligence and reading skills.
• Conclusion : Ben is fictional .​​

12. SNAP25 (SNP rs363050) = AA

• Effect : Essential for working memory and attention  , supporting high-level cognitive functions.
• Conclusion : Ben is fictional .​​

13. CACNA1C (SNP rs1006737) = AG

• Effect : The A allele  contributes to cognitive functions, while the G allele  helps balance brain activities.
• Conclusion : Partially beneficial .​​​

14. FKBP5 (SNP rs1360780) = TC

• Effect : The T allele  may increase vulnerability to stress, but strong emotional regulation from other SNPs compensates for this vulnerability.
• Conclusion : Neutral / Compensated.

Final Conclusion : Genetic Impact and Balance

This case study reveals a genetic profile  that combines beneficial and partially beneficial SNPs , acting in a homeostatic manner. Partially beneficial SNPs, in combination with other 100% beneficial alleles, help in a more precise control  of cognition and behavior, avoiding excesses or neuronal overload. In addition, factors related to child development, such as breastfeeding and type of delivery, although not directly included here, certainly contribute to the formation and support of the overall genetic profile.

This balance between high cognitive intelligence  and emotional control is the key factor that explains the success of this individual, both in terms  of professional achievements and in terms of emotional resilience  and adaptation in high –  pressure situations .

Reference​​

1. Correa, MA, et al.  A genome-wide association study for extremely high intelligence. Molecular Psychiatry , 2016. Available at: https://doi.org/10.1038/mp.2017.121 .
2. Zabaneh, D., et al.  A genome-wide association study for extremely high intelligence. Molecular Psychiatry , 2017. Available at: https://doi.org/10.1038/mp.2017.121 .
3. Cargill, M., et al.  Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature Genetics , 1999. Available at: https://doi.org/10.1038/10290.
4. Glatt, CE, et al.  Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Nature Genetics , 2001. Available at: https://doi.org/10.1038/86948.
5. Cavalleri, G., et al.  Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types: a case-control study. The Lancet Neurology , 2007. Available at: https://doi.org/10.1016/S1474-4422(07)70247-8.
6. Ng, M., et al.  Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. The Journal of Clinical Endocrinology and Metabolism , 2010. Available at: https://doi.org/10.1210/jc.2009-2077.
7. Hartmann, J., et al.  FKBP51 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior by altered glucocorticoid sensitivity and stress hormone release. Cell Metabolism , 2016. Available at: https://doi.org/10.1016/j.cmet.2016.04.016.

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