Evaluating the role of common risk variation in the recurrence risk of schizophrenia in multiplex schizophrenia families.
Evaluating the role of common risk variation in the recurrence risk of schizophrenia in multiplex schizophrenia families.
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DOI：
10.1038/s41398-022-02060-3
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发表时间：
2022-07-21
影响因子：
6.8
通讯作者：
Riley BP
中科院分区：
文献类型：
--
作者：
Ahangari M;Gentry AE;Irish Schizophrenia Genomics Consortium;Nguyen TH;Kirkpatrick R;Verrelli BC;Bacanu SA;Kendler KS;Webb BT;Riley BP
与散发病例的家族相比，多重家族有更高的精神分裂症复发风险，但这种复发风险增加的来源尚不清楚。我们使用精神分裂症全基因组关联研究数据（N = 156，509）构建了来自257个多重精神分裂症家族、2114个祖先匹配的散发病例和2205个人群对照的1005个个体的多基因风险评分（PRS），以评估PRS增加是否可以解释多重家族中精神分裂症复发风险高于祖先匹配的散发病例。使用混合效应logistic回归，将家族结构建模为随机效应，我们发现家族性病例的SCZ PRS与有或无精神病家族史（FH）的散发病例无显著差异（所有散发病例p = 0.90，FH+病例p = 0.88，FH−病例p = 0.82）。这些结果表明，增加负担的常见精神分裂症的风险变化，目前SCZ PRS指数，是不太可能占较高的复发风险的精神分裂症在多重家庭。在没有PRS升高的情况下，罕见的风险变异或家庭特有的环境影响的分离可能解释了家族复发风险的增加。这些研究结果也进一步验证了遗传影响的精神病谱，所示的共同SCZ风险变异负担的持续增加，从未受影响的亲属精神分裂症的情况下，在多重家庭。最后，这些结果表明，共同的风险变异负荷是不太可能的指数先证者的家庭精神分裂症复发风险的预测，和遗传风险的其他组成部分，必须加以确定，包括以提高复发风险的预测。
Multiplex families have higher recurrence risk of schizophrenia compared to the families of sporadic cases, but the source of this increased recurrence risk is unknown. We used schizophrenia genome-wide association study data (N = 156,509) to construct polygenic risk scores (PRS) in 1005 individuals from 257 multiplex schizophrenia families, 2114 ancestry-matched sporadic cases, and 2205 population controls, to evaluate whether increased PRS can explain the higher recurrence risk of schizophrenia in multiplex families compared to ancestry-matched sporadic cases. Using mixed-effects logistic regression with family structure modeled as a random effect, we show that SCZ PRS in familial cases does not differ significantly from sporadic cases either with, or without family history (FH) of psychotic disorders (All sporadic cases p = 0.90, FH+ cases p = 0.88, FH− cases p = 0.82). These results indicate that increased burden of common schizophrenia risk variation as indexed by current SCZ PRS, is unlikely to account for the higher recurrence risk of schizophrenia in multiplex families. In the absence of elevated PRS, segregation of rare risk variation or environmental influences unique to the families may explain the increased familial recurrence risk. These findings also further validate a genetically influenced psychosis spectrum, as shown by a continuous increase of common SCZ risk variation burden from unaffected relatives to schizophrenia cases in multiplex families. Finally, these results suggest that common risk variation loading are unlikely to be predictive of schizophrenia recurrence risk in the families of index probands, and additional components of genetic risk must be identified and included in order to improve recurrence risk prediction.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1073/pnas.1424958112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Ament, Seth A.;Szelinger, Szabolcs;Roach, Jared C.
通讯作者：
Roach, Jared C.
影响因子：
--
作者：
Cannon, TD;Kaprio, J;Koskenvuo, M
通讯作者：
Koskenvuo, M
影响因子：
11
作者：
Homann, O. R.;Misura, K.;DeLisi, L. E.
通讯作者：
DeLisi, L. E.