rs653178

This prospective nested case-control study examined 17 single nucleotide polymorphisms related to free thyroxine (fT4) and thyroid peroxidase antibody (TPO-Ab) levels in 865 breast cancer cases and 3,193 controls from the Malmö Diet and Cancer Study. The main findings identified fT4-related SNPs rs2235544 (DIO1 gene, OR for breast cancer risk in low fT4 women) and rs6485050, as well as TPO-Ab-related SNPs rs11675434, rs3094228, rs1033662, rs301806, and rs2071403 as potentially associated with breast cancer risk. The most promising association was rs2235544 (DIO1), where the C allele was associated with lower fT4 levels and increased breast cancer risk, particularly in women with low fT4 levels, suggesting a potential causal relationship.

This meta-analysis of 22,233 CAD cases and 64,762 controls tested 41 celiac disease-associated SNPs for association with coronary artery disease (CAD). While 58.5% of celiac disease risk alleles showed positive association with CAD (OR 1.001-1.081), this was not significantly different from the 50% expected by chance (p=0.069). Only rs653178 at the SH2B3/ATXN2 locus achieved study-wide statistical significance (OR 1.081, p=2.2×10⁻⁶), likely through pleiotropic effects. The findings provide no convincing evidence that genetic variants associated with celiac disease contribute to CAD risk.

A genome-wide association study (GWAS) of platelet count (PLT) and mean platelet volume (MPV) in 13,582 and 6,291 participants respectively from the eMERGE network identified 5 chromosomal regions associated with PLT and 8 with MPV at genome-wide significance (P<5E-8). Key findings include variants in ARHGEF3 (rs1354034, P=6E-24 for PLT; P=9E-34 for MPV), SH2B3 (rs3184504, P=5E-12), and multiple other loci. The study replicated 20 SNPs for PLT and 22 for MPV from prior meta-analyses and demonstrated pleiotropic effects with myocardial infarction, autoimmune, and hematologic disorders through phenome-wide association study (PheWAS).

Genome-wide association study of plasma beta-2 microglobulin (B2M) levels in 6,738 European Americans identified two genome-wide significant loci: the HLA region on chromosome 6 (rs9264638, p=1.8×10⁻²³) and SH2B3 on chromosome 12 (rs3184504, p=3.1×10⁻⁸). Six index SNPs in the HLA region accounted for 3.2% of log(B2M) variance and their associations were largely explained by imputed classical HLA alleles (HLA-A, HLA-B, HLA-C). The HLA locus was not associated with estimated glomerular filtration rate, while the SH2B3 locus had previously been implicated as an eGFR locus, confirming B2M as a kidney function biomarker.

This meta-analysis of 7 genome-wide association studies identified three novel multiple sclerosis susceptibility loci: rs170934 near EOMES (3p24.1, OR=1.17, P=1.6×10⁻⁸), rs2150702 in MLANA (9p24.1, OR=1.16, P=3.3×10⁻⁸), and rs6718520 near THADA (2p21, OR=1.17, P=3.4×10⁻⁸). The analysis encompassed 5,545 cases and 12,153 controls and identified 10 additional loci with suggestive evidence of association (P<1×10⁻⁶), including IL12B, TAGAP, PLEK, and ZMIZ1, which are shared with other inflammatory diseases.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.