rs6265

Mechanism

The C (major) allele is associated with:

• CC has about 20 minutes more Slow wave sleep (stage 3/4) and increased sleep intensity compared to CT. (R)
• CC showed better response accuracy than T on a verbal 2-back working memory task.(R)
• CC vs TT+CT had 19.3 vs 17.0 of BDNF, not too significant of a difference. (R) But, other factors of BDNF are also altered.
• In Chinese, CC had higher performance in digital working memory and spatial localization than TT. (R)
• CC had higher mean intelligence. (R)
• CC responds better to repetitive transcranial magnetic stimulation, with drug resistant depression .(R)
• CC preferentially sought positive emotions (e.g., happy faces) and had stronger reaction tonegativeemotions (e.g., angry, fearful, and sad faces) compared to CT. (R)
• Airplane Pilots with a T allele had their scores on flight simulations drop twice as fast than those without the T allele. BDNF and NAA levels dropped significantly more in people with the T allele.(R)
• CC (compared to TT) show reduced stress-induced anxiety-like behavior. (R)
• CC subjects scored higher on trait-anxiety and neuroticism (not significant) compare to CTor TT(R), but other studies have not found an association with Neuroticism (R).
• CC has higher risk of depression (1.7X). (R)
• CC has higher risk for allergies. Increased levels of BDNF in blood, lung fluidand nose fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. (R)
• In men, CC had twice the risk of being overweight compared to people with a T. Women with CC was 50% less likely to be overweight than people with a T allele.(R)
• Men with CC who consumed more PUFA  weighed less (more than 8.76% of calories). (R)
• Women with CC weighed less as well when they consumed more PUFA (more than 8.76% of calories), but this wasnt statistically significant. (R)
• In men, CC showed a larger increase in salivary cortisol than CT in response to stress.(R)
• However, only CC with higher levels of cortisol had depression, but not CT. (R) 
• As mentioned above, CC has about 20 minutes more slow wave sleep (stage 3/4) and increased sleep intensity compared to CT. (R)
• When awake, CC had about double the EEG alpha waves(9.75-11.75 Hz) compared to the CT genotype subjects (both in a rested and also a sleep-deprived state).(R)

• CC had the most slow wave activity in the first slow wave cycle. However, slow wave activity tended to decline more in CC compared to CT in subsequent cycles.(R)

The T (minor) allele is associated with:

• TT have lower BMI compared to the two other genotypes.(R)
• The T allele is associated with lower systolic blood pressure. (R)
• The T allele is maybe less susceptible to degenerative neurological disorders like Parkinsons, Huntingtons, Lupus, MS (R, R2)
• The T allele may also be protective against depression when subjected to repeated defeat.(R)
• The T allele carriers had a lower incidence of decreased sexual desire (OR = 0.32, p = 0.01) as compared to the CC. (R)
• The T allele preserves gray matter volume in MS.(R)
• The T allele possibly has decreased hippocampal volume in some cases. However, in a large cohort of healthy human subjects, T was not associated with hippocampal structure or memory performance at all. (R)
• TT has more anxiety. (R)
• TT are more introverted, depression resistant, impaired motor skills learning (R)
• The T allele is associated with introversion (R, R2). Since the T allele is more common amongst Asians, its thought that this is part of the explanation for increased introversion amongst Asians. (R)
• T may lead to impaired learning and memory. (R)
• T has worse motor skills and is more likely to get into car accident (R)
• T is a slower stroke-victim recoverer (R)
• The T allele makes people more likely to binge eat after dietary restriction. (R)
• The T allele numerically revealed a reduced overall performance in the verbal learning memory test, but this did not turn out to be statistically significant. (R)
• TT had significantly lower N-acetyl aspartate and Glutamate metabolic ratios compared with CC. Difference between CTand CCwas negligible. BDNF may exert its observed effects on NAA via its influence on the glutamate system.(R)
• The CT and TT genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. TT showed a 19% increased risk of schizophrenia compared to AG. (R)
• The presence of a Tallele isassociated with a poorer executive functioning in OCD. (R)
• T=Higher Alzheimers risk in non-APOE4 carriers. (R)
• CT was associated with both ADHD and Intellectual disability, and the C allele was significantly associated with ADHD. (R)
• Depressed patients who had CT or TT showed significantly increased risk of suicidal behavior.
• The T allele causes higher risk of alcohol related depression. (R)
• The T allele increases bipolar risk, but Ts respond better to treatment. (R)
• The T alleles recalled lower percentage of positive words in childhood. (R)
• Non-significant: Meta-analysis 6% increased risk for depression TT vs CC. 3% decreased risk comparing CT with CC genotypes. (R)
• T allele carriers are particularly sensitive to Childhood adversity. The T allele had less gray matter compared to CCs with childhood adversity.
• The T allele had higher heart disease related depression. (R)
• Carriers of the T allele showed a significantly reduced HPA axis/stress response to psychosocial stressors compared with individuals with the CC genotype. (R)
• TT had significantly lower N-acetyl aspartate and Glutamate metabolic ratios compared with CC. BDNF may exert its observed effects on NAA via its influence on the glutamate system.(R)

Mechanism

• The T allele is associated with abnormal packaging of the precursor of BDNF and decreased mature BDNF production in cells [R, R].

The T (minor) allele is associated with:

• Lower BMI compared to the two other genotypes (TT) [R].

• Lower systolic blood pressure [R].

• Lower susceptibility to degenerative neurological disorders like Parkinsons, Huntingtons, Lupus, MS [R, R2].

• Protection against depression when subjected to repeated defeat [R].

• Lower incidence of decreased sexual desire (OR = 0.32, p = 0.01) as compared to the CC [R].

• Preserved gray matter volume in MS [R].

• Decreased hippocampal volume in some cases but not all [R].

• More anxiety (TT) [R].

• Introversion, depression resistant, impaired motor skills learning (TT) [R].

• Introversion [R, R2]: the T allele is prevalent amongst Asians, which might explain increased introversion amongst Asians. [R].

• Impaired learning and memory [R].

• Worsened motor skills and increased likelihood of getting into a car accident [R].

• Lengthened recovery time for stroke victims [R].

• Increased likelihood of binge eating after dietary restriction [R].

• Reduced overall performance in the verbal learning memory test, although not statistically significant [R].

• Significantly lower N-acetyl-aspartate and Glutamate metabolic ratios compared with CC (TT). The difference between CT and CC was negligible. BDNF may exert its observed effects on NAA via its influence on the glutamate system [R].

• A 33% increased risk of developing eating disorders, while also having a 21% protective effect in substance-related disorders (CT and TT). TT showed a 19% increased risk of schizophrenia compared to AG [R].

• Poorer executive functioning in OCD [R].

• Higher Alzheimer’s risk in non-APOE4 carriers [R].

• Increased risk of suicidal behavior in depressed patients who had CT or TT.

• Higher risk of alcohol-related depression [R].

• Increased bipolar risk, although T responds better to treatment [R].

• Recollection of a lower percentage of positive words in childhood [R].

• Non-significant: Meta-analysis 6% increased the risk for depression TT vs CC. 3% decreased risk comparing CT with CC genotypes [R].

• Sensitivity to Childhood adversity. The T allele has less gray matter compared to CCs with childhood adversity.

• Higher heart disease-related depression [R].

• Significantly reduced HPA axis/stress response to psychosocial stressors compared with individuals with the CC genotype [R].

• Significantly lower N-acetyl-aspartate and Glutamate metabolic ratios compared with CC (TT). BDNF may exert its observed effects on NAA via its influence on the glutamate system [R].

• Increased exercise participation due to positive attitiudes, increased motivation,and a reduced desire to stop once exercising [R, R].

The C (major) allele is associated with:

• 20 minutes more slow-wave sleep (stage ¾) and increased sleep intensity compared to CT (CC) [R].

• Double the EEG alpha waves (9.75-11.75 Hz) compared to the CT genotype subjects (both in a rested and also a sleep-deprived state)  (CC) [R].

• The slowest wave activity in the first slow wave cycle. Slow wave activity tended to decline more in CC compared to CT in subsequent cycles (CC) [R].

• Better response accuracy than T on a verbal 2-back working memory task (CC) [R].

• 19.3 of BDNF in CC compared to 17.0 of BDNF in TT and CT, not too significant of a difference [R]. Other factors of BDNF are also altered.

• Higher performance in digital working memory and spatial localization than TT in Chinese (CC) [R].

• Higher mean intelligence [R].

• Better response to repetitive transcranial magnetic stimulation, with drug-resistant depression (CC) [R].

• Seeking positive emotions (e.g., happy faces) and having a stronger reaction to negative emotions (e.g., angry, fearful, and sad faces) compared to CT (CC) [R].

• Reduced stress-induced anxiety-like behavior (CC) compared to TT [R]. 

• Higher scores on trait-anxiety and neuroticism (not significant) compare to CT or TT (CC) [R], although other studies have not found an association with Neuroticism [R].

• Higher risk of depression (1.7X) [R].

• Higher risk for allergies (CC). Increased levels of BDNF in blood, lung fluid, and nose fluid positively correlate with disease activity and severity in patients with allergic rhinitis [AR], asthma and atopic eczema [R].

• ADHD while CT is associated with both ADHD and intellectual disability [R].

• Twice the risk of being an overweight male compared to those with a T allele (CC). Women with CC were 50% less likely to be overweight than people with a T allele were [R].

• The lower weight of men who consumed more PUFA (more than 8.76% of calories) (CC) [R]. 

• The lower weight of women who consumed more PUFA (more than 8.76% of calories), although not statistically significant (CC) [R].

• A greater increase in salivary cortisol than CT in response to stress in men (CC) [R].

• Depression in individuals with higher levels of cortisol in CC but not CT [R].