A two-stage GWAS found the genetic loci behind serum complement C3 and C4 levels — proteins central to the immune system's complement pathway — with an unusually clean match to this page's own variants.
Complement C3 and C4 are proteins central to the complement system, a branch of the immune system that helps clear pathogens and damaged cells. Their blood levels are used clinically to help investigate certain autoimmune and infectious conditions, and — like most blood proteins — vary continuously across the population, shaped partly by genetics.
Yang et al. 2012 ran a two-stage GWAS of serum C3 and C4 levels in 1,999 healthy Chinese men, with replication in 1,496 more. For C3, the study found rs3745567, directly in the C3 gene, and a signal near CFH. For C4, an entire genomic region at 6p21.3 reached significance, spanning eight SNPs: two in the MHC class I region (HLA-A, HLA-C, HLA-B), four in the MHC class II region (HLA-DRA, HLA-DRB, HLA-DQB), and two flanking the C4 gene directly. The study also found that participants positive for hepatitis B surface antigen had significantly lower C3 and C4 levels than those who were negative.
This page's own 7 variants match the paper's own named SNPs one for one: rs3753394 near CFHR1 (the same region as the paper's CFH finding), rs3745567 in C3 itself, rs11575839 in HLA-C, rs2071278 in HLA-DRA, rs3763317 in HLA-DRB, rs241428 in HLA-DQB, and rs2857009 flanking C4 directly.
Complement C3 and C4 are measured directly with a blood test, not estimated from genotype, and no variant on this page is used clinically to interpret a complement test. Complement levels help investigate specific autoimmune and infectious conditions in a clinical setting — a role none of these variants fills.
Complement testing is ordered and interpreted by clinicians investigating specific conditions (such as certain autoimmune diseases or recurrent infections). Nothing on this page changes that clinical workflow.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Complement C3 and C4 Levels comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 7 of 7 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Complement C3 and C4 Levels. MyGeneLog™. https://www.mygenelog.com/conditions/complement-c3-c4-levels
C3 and C4 are proteins central to the complement system, a branch of the immune system that helps clear pathogens and damaged cells. Their blood levels are used clinically to help investigate certain autoimmune and infectious conditions.
In 1,999 Chinese men (replicated in 1,496 more), it found variants in C3 and near CFH associated with C3 levels, and an entire genomic region spanning the HLA genes and flanking the C4 gene associated with C4 levels.
No. Complement testing is a clinical tool used to investigate specific conditions — this page describes population-level genetic contributions to baseline complement levels, not a diagnostic test.
No individual variant does. These are population-level statistical associations, and complement levels are measured directly with a blood test, not estimated from genotype.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.