Single-nucleotide polymorphism (SNP)

A single-nucleotide polymorphism (SNP, pronounced "snip") is a germline variation at a single base-pair position where two or more nucleotide alleles occur at a population frequency above 1%. The human genome contains roughly 4–5 million common SNPs — on average one per 500–1,000 base pairs — genotyped using microarray chips querying hundreds of thousands of positions. SNPs are the primary markers in genome-wide association studies (GWAS), testing hundreds of thousands of variants against a trait or disease across tens or hundreds of thousands of participants — a statistical scan rather than mechanistic proof of causation. Because nearby SNPs are inherited together in blocks of high linkage disequilibrium (LD), a single tag SNP can proxy an entire haplotype, reducing genotyping cost without sacrificing discovery power, as demonstrated by the Phase II HapMap (Frazer et al., 2007). In aging genetics, common SNPs with individually small effects aggregate into polygenic risk scores explaining a meaningful fraction of lifespan variance — Yashin et al. (2012) identified 27 SNPs with consistent additive effects on life span across independent cohorts, implicating cell-growth, apoptosis, and other biological pathways. SNPs differ from rare variants (minor allele frequency below 1%), which GWAS arrays mostly miss and are better captured by whole-genome or whole-exome sequencing. Whether rare variants account for the heritability unexplained by common SNPs ("missing heritability") remains an open question.