Nyholt Dale R, Gillespie Nathan G, Merikangas Kathleen R, Treloar Susan A, Martin Nicholas G, Montgomery Grant W
Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, QLD, Australia.
Genet Epidemiol. 2009 Feb;33(2):105-13. doi: 10.1002/gepi.20361.
We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12-2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2)=0.17, 95% CI: 0.08-0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes.
我们在已知最大的包含多名经手术确诊患有子宫内膜异位症女性的家系集合中，以及在一个由815对同卵女性双胞胎和457对异卵女性双胞胎组成的独立样本中，研究了偏头痛与子宫内膜异位症的共现情况。在子宫内膜异位症家系中，与未患子宫内膜异位症的女性相比，患子宫内膜异位症的女性出现偏头痛性头痛的风险显著增加（优势比[OR]为1.57，95%置信区间[CI]：1.12 - 2.21，P = 0.009）。双变量遗传力分析表明，没有证据显示存在影响偏头痛或子宫内膜异位症的共同环境因素，但这两种性状都有显著的遗传成分，遗传力估计值分别为69%和49%。重要的是，在偏头痛和子宫内膜异位症之间观察到显著的加性遗传相关性（r(G) = 0.27，95% CI：0.06 - 0.47）和双变量遗传力（h(2)=0.17，95% CI：0.08 - 0.27）。控制人格特质神经质对这种关联影响不大。这些结果证实了先前报道的偏头痛与子宫内膜异位症之间的共病情况，并表明共同的遗传影响完全可以解释它们在个体中的共现。鉴于子宫内膜异位症的药物治疗通常针对激素途径，并且许多研究结果支持激素变化与偏头痛之间的关系，激素相关基因和途径很可能是偏头痛和子宫内膜异位症的共同候选因素。因此，考虑偏头痛和子宫内膜异位症的状况可能为识别其潜在基因提供新的机会。最后，我们提出对这种遗传相关的共病性状进行分析，可以通过使用更特异、同质且可遗传的表型来提高检测遗传风险位点的能力。
