Meta-analysis and prioritization of human skin pigmentation-associated GWAS-SNPs using ENCODE data-based web-tools

Area of Science:

• Genetics
• Human Biology
• Genomics

Background:

• Human skin pigmentation is a complex trait with wide population variations.
• The genetic underpinnings and functional roles of variants influencing skin pigmentation remain largely unknown.
• Genome-Wide Association Studies (GWAS) have identified numerous genomic variants associated with skin pigmentation, but their functional implications are often unclear.

Purpose of the Study:

• To analyze and prioritize 519 non-coding and 24 3'UTR Single-Nucleotide Polymorphisms (SNPs) associated with human skin pigmentation.
• To annotate potential pigmentation-related functionalities to these prioritized SNPs.
• To advance the understanding of the molecular basis of human skin pigmentation variation.

Main Methods:

• Utilized data from 14 human skin pigmentation-related GWAS.
• Employed ENCODE-based web tools, including rSNPBase, RegulomeDB, and HaploReg, for SNP analysis.
• Incorporated experimentally validated evidence into the prioritization and annotation process.

Main Results:

• Successfully prioritized pigmentation-associated GWAS-SNPs using an in-silico approach.
• Annotated potential pigmentation-related functions for the analyzed SNPs.
• Identified key SNPs that may play a role in modulating skin pigmentation phenotype.

Conclusions:

• This study provides a prioritized list of SNPs and their potential functional annotations related to human skin pigmentation.
• The findings pave the way for deeper investigation into the molecular mechanisms underlying skin color diversity.
• This work represents a significant step towards elucidating the genetic architecture of human skin pigmentation.