The leptin signal is transduced via the JAK2‐STAT3 (Janus kinase 2‐signal transducer and activator of transcription‐3) pathway at the leptin receptor. JAK2 also phosphorylates insulin receptor substrate, integral to insulin and leptin action and is required for optimum adenosine triphosphate–binding cassette transporter A1 (ABCA1)‐dependent transport of lipids from cells to apolipoprotein A‐1 (apoA‐I). We hypothesized that common variation in the JAK2 gene may be associated with body fat, insulin sensitivity, and modulation of the serum lipid profile in the general population. Ten tagging single‐nucleotide polymorphisms (SNPs) spanning the gene were genotyped in 2,760 white female twin subjects (mean age 47.3 ± 12.6 years) from the St Thomas’ UK Adult Twin Registry. Minor allele frequencies were between 0.170 and 0.464. The major allele of rs7849191 was associated with higher central fat (P = 0.030), percentage of central fat (P = 0.014) and waist circumference (P = 0.027) the major allele of rs3780378 with higher serum apoA (P = 0.026), total cholesterol (P = 0.014), low‐density lipoprotein (LDL) cholesterol (P = 0.012) and lower triglyceride (P = 0.023). However, no associations were significant at a level which took account of multiple testing. Although JAK2 is a critical element in leptin and insulin signaling and has a role in cellular cholesterol transport, we failed to establish associations of common SNPs with relevant phenotypes in this human study.