MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls.
MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls.
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DOI：
10.1038/tp.2016.286
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发表时间：
2017-01-24
影响因子：
6.8
通讯作者：
Donohoe G
中科院分区：
文献类型：
--
作者：
Cosgrove D;Harold D;Mothersill O;Anney R;Hill MJ;Bray NJ;Blokland G;Petryshen T;Wellcome Trust Case Control Consortium;Richards A;Mantripragada K;Owen M;O'Donovan MC;Gill M;Corvin A;Morris DW;Donohoe G
Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.
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影响因子：
4.5
作者：
Hill MJ;Donocik JG;Nuamah RA;Mein CA;Sainz-Fuertes R;Bray NJ
通讯作者：
Bray NJ
影响因子：
5.7
作者：
Eickhoff, Simon B.;Heim, Stefan;Amunts, Katrin
通讯作者：
Amunts, Katrin
影响因子：
2.5
作者：
Kelly, Sinead;Morris, Derek W.;Donohoe, Gary
通讯作者：
Donohoe, Gary
影响因子：
14.9
作者：
Cunningham F;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt SE;Janacek SH;Johnson N;Juettemann T;Kähäri AK;Keenan S;Martin FJ;Maurel T;McLaren W;Murphy DN;Nag R;Overduin B;Parker A;Patricio M;Perry E;Pignatelli M;Riat HS;Sheppard D;Taylor K;Thormann A;Vullo A;Wilder SP;Zadissa A;Aken BL;Birney E;Harrow J;Kinsella R;Muffato M;Ruffier M;Searle SM;Spudich G;Trevanion SJ;Yates A;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
4.5
作者：
Cousijn, Helena;Eissing, Marc;Fernandez, Guillen;Fisher, Simon E.;Franke, Barbara;Zwiers, Marcel;Harrison, Paul J.;Arias-Vasquez, Alejandro
通讯作者：
Arias-Vasquez, Alejandro