A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes

Majumdar, Arunabha and Patel, Preksha and Pasaniuc, Bogdan and et al, . (2022) A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes. European Journal of Human Genetics, 30 (5). pp. 547-554. ISSN 1018-4813

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In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic association signals between 5-HTTLPR and psychiatric phenotypes, however, have been inconsistent across many studies. Since the polymorphism cannot be tested via available SNP arrays, we had previously proposed an efficient machine learning algorithm to predict the genotypes of 5-HTTLPR based on the genotypes of eight nearby SNPs, which requires access to individual-level genotype and phenotype data. To utilize the advantage of publicly available GWAS summary statistics obtained from studies with very large sample sizes, we develop a GWAS summary-statistics-based approach for testing the variable number of tandem repeat (VNTR) associations with various phenotypes. We first cross-verify the accuracy of the summary-statistics-based approach for 61 phenotypes in the UK Biobank. Since we observed a strong similarity between the predicted individual-level 5-HTTLPR genotype-based approach and the summary-statistics-based approach, we applied our method to the available neurobehavioral GWAS summary statistics data obtained from large-scale GWAS. We found no genome-wide significant evidence for association between 5-HTTLPR and any of the neurobehavioral traits. We did observe, however, genome-wide significant evidence for association between this locus and human adult height, BMI, and total cholesterol. Our summary-statistics-based approach provides a systematic way to examine the role of VNTRs and related types of genetic polymorphisms in disease risk and trait susceptibility of phenotypes for which large-scale GWAS summary statistics data are available. © 2021, The Author(s).

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IITH Creators:
IITH CreatorsORCiD
Majumdar, Arunabhahttps://orcid.org/0000-0002-5609-075X
Item Type: Article
Additional Information: This study was supported by funding R01 MH115676 (BP and RAO) and RF1 AG058484 (RAO)
Uncontrolled Keywords: psychiatric disorders, pre-genome-wide association study (GWAS), serotonin transporter (SLC6A4) promoter polymorphism,a 43-base-pair insertion/deletion polymorphism
Subjects: Others > Psychology
Divisions: Department of Mathematics
Depositing User: . LibTrainee 2021
Date Deposited: 30 Jun 2022 07:03
Last Modified: 01 Jul 2022 09:42
URI: http://raiith.iith.ac.in/id/eprint/9437
Publisher URL: http://doi.org/10.1038/s41431-021-00996-6
OA policy: https://v2.sherpa.ac.uk/id/publication/1639
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