Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea

Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10^-8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition.