Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Neuron. 2018 May 16;98(4):743-753.e4. doi: 10.1016/j.neuron.2018.04.014. Epub 2018 May 3.
Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.
复杂特征，包括偏头痛，通常在家族中聚集，但这种现象背后的遗传结构尚不清楚。这种聚集可能是由罕见的、外显率高的变异引起的，这些变异根据孟德尔遗传规律分离，也可能是由常见变异的充分多基因积累引起的，每个变异的个体效应都很小，或者是这两种假设的结合。在 1589 个偏头痛家族的 8319 个人中，我们计算了偏头痛多基因风险评分（PRS），并发现家族性病例的常见变异负担显著更高（n=5317，OR=1.76，95%CI=1.71-1.81，p=1.7×10），与来自 FINRISK 队列的人群病例（n=1101，OR=1.32，95%CI=1.25-1.38，p=7.2×10）相比。PRS 解释了人群病例中 1.6%的表型方差和家族性病例中 3.5%的表型方差（包括无先兆偏头痛的 2.9%，有先兆偏头痛的 5.5%，偏瘫性偏头痛的 8.2%）。结果表明，常见多基因变异对偏头痛的家族聚集有显著贡献。
Zotero 插件