Multi-allelic pathogenic locus — both H90P (T>G) and H90R (T>C) disrupt the DYRK1B DH box, causing AOMS3 (early-onset central obesity, type 2 diabetes, hypertension, coronary artery disease) via impaired kinase maturation

Intronic variant in SIRT1 affecting NAD-dependent deacetylase expression and oxidative stress protection

Strongest GWAS thyroid locus — regulatory variant near FOXE1 affecting thyroid development, TSH levels, and differentiated thyroid cancer risk

Promoter variant in FADS2 that increases delta-6 desaturase (D6D) expression via ELK1 transcription factor binding; the minor T allele elevates D6D activity, accelerating conversion of dietary omega-6 and omega-3 precursors to long-chain PUFAs.

Synonymous variant in SPINK5 exon 13 that tags the same risk haplotype as the nearby functional Lys420Glu variant (rs2303067), associated with atopic dermatitis susceptibility through linkage disequilibrium rather than a direct protein-altering effect

Missense variant at position 308 of the orexin receptor 2 protein; the minor Ile308 allele (A) reduces receptor activity, increasing daytime napping tendency, while placing the variant directly at a drug target for orexin antagonist sleep medications

Intronic variant in KDM4A histone demethylase associated with problematic opioid prescription use in a 132,113-participant GWAS

Lactase persistence - ability to digest lactose (milk sugar) in adulthood

Intronic HNF4A tag SNP associated with altered bile acid synthesis regulation through modified HNF4A-driven CYP7A1 expression; linked to primary biliary cholangitis progression in a single Japanese cohort study

Intronic variant in the CST complex component STN1/OBFC1 that influences telomere length; the C allele drives longer telomeres and elevated cancer risk while the A allele predisposes to shorter telomeres and accelerated cellular aging