Children’s Greenness Exposure and IQ-Associated DNA Methylation: A Prospective Cohort Study

Abstract

Epigenetics is known to be involved in regulatory pathways through which greenness exposure influences child development and health. We aimed to investigate the associations between residential surrounding greenness and DNA methylation changes in children, and further assessed the association between DNA methylation and children’s intelligence quotient (IQ) in a prospective cohort study. We identified cytosine-guanine dinucleotide sites (CpGs) associated with cognitive abilities from epigenome- and genome-wide association studies through a systematic literature review for candidate gene analysis. We estimated the residential surrounding greenness at age 2 using a geographic information system. DNA methylation was analyzed from whole blood using the HumanMethylationEPIC array in 59 children at age 2. We analyzed the association between greenness exposure and DNA methylation at age 2 at the selected CpGs using multivariable linear regression. We further investigated the relationship between DNA methylation and children’s IQ. We identified 8743 CpGs associated with cognitive ability based on the literature review. Among these CpGs, we found that 25 CpGs were significantly associated with greenness exposure at age 2, including cg26269038 (Bonferroni-corrected p ≤ 0.05) located in the body of SLC6A3, which encodes a dopamine transporter. DNA methylation at cg26269038 at age 2 was significantly associated with children’s performance IQ at age 6. Exposure to surrounding greenness was associated with cognitive ability-related DNA methylation changes, which was also associated with children’s IQ. Further studies are warranted to clarify the epigenetic pathways linking greenness exposure and neurocognitive function.

Residential green space in association with the methylation status in a CpG site within the promoter region of the placental serotonin receptor HTR2A

“…[1][2][3] However, as described by the hypothesis of Developmental Origins of Health and Diseases" (DoHaD), some of these observed associations could already originate during fetal development [4][5][6][7] , which is considered an important phase in which the brain develops and neurocognitive maturation takes place. [8,9] A proposed way through which green space could influence child (neuro)development is by affecting epigenetic mechanisms [10,11] , such as DNA methylation, thereby shaping early-life conditions and development. [12][13][14] For example, a recent study by Lee et al (2021) provided evidence for an association between residential green space and cognitive ability-related DNA methylation in children.…”

“…[8,9] A proposed way through which green space could influence child (neuro)development is by affecting epigenetic mechanisms [10,11] , such as DNA methylation, thereby shaping early-life conditions and development. [12][13][14] For example, a recent study by Lee et al (2021) provided evidence for an association between residential green space and cognitive ability-related DNA methylation in children. [10] Given this knowledge it is particularly interesting to investigate the epigenetics that take place within the placenta, as they can be readily influenced by the maternal environment.…”

“…[12][13][14] For example, a recent study by Lee et al (2021) provided evidence for an association between residential green space and cognitive ability-related DNA methylation in children. [10] Given this knowledge it is particularly interesting to investigate the epigenetics that take place within the placenta, as they can be readily influenced by the maternal environment. [15][16][17] The placenta is a key mediator during intrauterine development.…”

“…[23,24] The serotonergic pathway is closely involved in fetal neurodevelopment [20,25,26] , and placental methylation changes in this serotonin receptor have been associated with infant neurobehavioral outcomes. [27] Considering green space is similarly closely involved in neuralrelated health outcomes and has been associated with cognitive ability-associated DNA methylation changes [10] , we hypothesize that green space exposure is capable of modifying the methylation status of an important target for cognitive development at an earlier time as measurable within placental tissue. To our knowledge, we are the first to investigate the association between green space and the placental methylation and hope to motivate future research into this field.…”

Early life exposure to residential green space impacts cognitive functioning in children aged 4 to 6 years

“…For instance, long-term exposure to green space was associated with a decreased risk of childhood-associated behavioral problems concerning emotion, conduct and hyperactivity ( Amoly et al, 2014 , Bijnens et al, 2020 , Markevych et al, 2014 ) and associated with a lower risk of psychiatric disorders as found in a large-scale study covering more than 900,000 Danish individuals ( Engemann et al, 2019 ). Additionally, studies found that children residing in an environment surrounded with more green could better memorize, were more attentive and had a higher intelligence quotient ( Bijnens et al, 2020 , Dadvand et al, 2017 , Lee et al, 2021 ). However, most studies investigating cognitive function and green space examined school-aged children aged six to 12, whereas observable differences in cognitive capabilities are already present at the preschool age, which is an important developmental stage in children ( National Research et al, 2000 ).…”