Dataset Information

Investigation of gene-environment interactions in relation to tic severity.

ABSTRACT: Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

SUBMITTER: Abdulkadir M

PROVIDER: S-EPMC8536549 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Abstract Objectives A genetic variant in peroxisome proliferator-activated receptor-gamma (PPARG2 Pro12Ala; rs1801282) has been linked to both carcinogenesis and lifestyle factors such as energy balance and fat intake and identified as modifiers of risk in several different cancers. However, to date, no systematic review has been conducted. We conducted a systematic literature review to summarize the current evidence on whether associations between lifestyle factors and risk of cancer are modified by the PPARG2 Pro12Ala variant. Methods We conducted a systematic literature review of studies published before July 2019 using the PubMed database. We included observational studies that: 1) included diet, anthropometrics and physical activity as lifestyle factors; 2) had the risk of incident cancer in any site as an outcome; 3) included controls (participants free of cancer); and 4) reported a statistical significance of interaction effects between the PPARG2 variant and lifestyle factors. Results After applying the inclusion criteria to 3424 identified abstracts, 14 studies of cancers in colon/rectum (n = 6), breast (n = 3), prostate (n = 3), pancreas (n = 1) and endometrium (n = 1) were selected, which included a total of 22,267 participants with 9290 cancer cases. Alcohol consumption had a statistically significant interaction with the PPARG2 variant in all three studies of colorectal and breast cancers investigating this interaction. Dietary factors such as fried food intake, refined grain intake, dietary vitamin A intake, lutein intake and Prudent dietary pattern significantly interacted with the PPARG2 variant, whereas other dietary factors such as dietary fat and meat intakes did not. Body mass index, waist-to-hip ratio and physical activity level did not significantly interact with the PPARG2 variant in all six studies of colorectal, breast, prostate, pancreatic and endometrial cancers, except for one study on body mass index and prostate cancer. Conclusions Our systematic review shows statistically significant, although inconsistent, interactions between PPARG2 Pro12Ala variant and lifestyle factors on cancer risk. This suggests that lifestyle recommendations for cancer prevention may need to be tailored based on genetic factors such as PPARG2 Pro12Ala variant. Funding Sources This study was funded by the OHSU/OSU Cancer Prevention and Control Initiative.

Dataset Information

Investigation of gene-environment interactions in relation to tic severity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets