Upstream promoter variant that reduces ADIPOQ transcription, lowering circulating adiponectin and increasing risk of type 2 diabetes under additive and dominant models

Synonymous CYP2D6 variant that causes allele dropout in standard CYP2D6*3 genotyping assays, potentially masking co-inherited non-functional alleles

Intronic variant in FADS2 that reduces delta-6 desaturase activity, impairing the first step of the PUFA desaturation cascade and lowering circulating EPA, DHA, and arachidonic acid while raising linoleic acid and ALA precursors

Promoter region variant affecting sex hormone-binding globulin levels, with the A allele increasing SHBG by 15-25% and influencing free testosterone and estradiol bioavailability

Upstream promoter-region ACE variant on a separate LD block from the I/D polymorphism — the C allele is associated with young-onset hypertension and sits in a haplotype context linked to higher cardiovascular and renal risk independent of ACE enzyme activity

Synonymous exon 2 variant that influences baseline C-reactive protein expression and inflammatory phenotypes

Gain-of-function missense variant in PCSK9 that increases intracellular LDL receptor degradation, causing autosomal dominant familial hypercholesterolemia

Intronic GPNMB variant that acts as a brain eQTL; the A allele increases GPNMB expression in cortex and putamen, conferring genome-wide significant Parkinson's disease risk and implicating lysosomal integrity and senescent cell biology in neurological aging

Intronic regulatory variant in IVD (isovaleryl-CoA dehydrogenase) associated with altered IVD expression, isovalerylcarnitine levels, and modest pulmonary fibrosis susceptibility

Intronic FBN1 variant associated with elevated thoracic aortic dissection risk through altered fibrillin-1 microfibril structure and TGF-β1 bioavailability