Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function.
ABSTRACT Several aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition.
700 Subjects (schizophrenia spectrum disorder, n=190, bipolar disorder n=157 and healthy individuals n=353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions.
Four SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p=1.55×10(-8); rs11056571, p=1.68×10(-8); and rs2300290, p=1.09×10(-8)). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p=4.32×10(-8)). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p=7.6×10(-14)).
We identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed.
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ABSTRACT: The purpose of this study is to characterize the expression profile of a novel gene WDR72 in laying hens. Sixty-week old Hy-line Brown layers with similar laying sequence, egg weight, and shell strength, were selected and divided into 5 groups. The oviduct segments, such as magnum, white isthmus, and uterus, were sampled from each group of hens which were killed at 3 h post-oviposition (3 h P.O.), 4.15-4.5 h P.O., 8.5-9 h P.O., 12 h P.O. and 18 h P.O., respectively. To the 8.5-9 h P.O. hens, additional organs were also sampled besides oviduct tissues. Moreover, another group of hens with weak shell strength were selected and their oviduct segments were sampled at 12 h P.O. Then the expression profile of WDR72 was analyzed using real-time quantitative RT-PCR. The results showed as follows. (1) WDR72 transcripts specifically distributed in parts of organs investigated. At 8.5-9 h P.O., WDR72 appeared to be much more abundantly expressed in hens' oviduct sections, then followed in turn by brain, kidney, lung, glandular stomach and spleen. However, there were almost no WDR72 transcripts expressed in pectoral muscle, liver, heart and jejunum. (2) During the process of an "egg" passing through an oviduct, the expression of WDR72 in the magnum was greatly superior to that in the other two oviduct segments at 3 h P.O., 8.5-9 h P.O., and 12 h P.O.; while it was white isthmus in which WDR72 transcript levels were the highest at 4.15-4.5 h P.O. and 18 h P.O. (3) To any oviduct segment, not only uterus but also magnum and white isthmus, the expression of WDR72 in which was significantly up-regulated at the stages of active calcification. (4) WDR72 transcript levels in any oviduct segments of strong-shell hens were significantly higher than that of weak-shell layers (P < 0.01), which arose the possibility that WDR72 was positively associated with chicken eggshell strength. In conclusion, the expression profile of WDR72 gene in laying hens has been characterized, which would facilitate to further probe into its functions.Molecular Biology Reports 05/2013; · 2.51 Impact Factor
Dataset: Froestl 2013 Part2
Dataset: Froestl 2013 Part2