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Shi Y.,Huazhong University of Science and Technology | Shi Y.,Shanghai Genome Pilot Institutes for Genomics and Human Health | Shi Y.,Changning Mental Health Center | Li L.,Guangxi Province Tumor Hospital | And 86 more authors.
Nature Genetics | Year: 2013

To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched = 9.69 × 10-9, per-allele odds ratio (OR)stringently matched = 1.26) and 17q12 (rs8067378, Pcombined, stringently matched = 2.00 × 10-8, per-allele ORstringently matched = 1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched = 4.52 × 10-27, per-allele ORstringently matched = 0.75). Our findings provide new insights into the genetic etiology of cervical cancer. © 2013 Nature America, Inc. All rights reserved.


Shi Y.,Shanghai JiaoTong University | Shi Y.,Shanghai GenomePilot Institutes for Genomics and Human Health | Shi Y.,Changning Mental Health Center | Li Z.,Shanghai JiaoTong University | And 51 more authors.
Nature Genetics | Year: 2011

Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10 -10) and 1q24.2 (rs10489202, P = 9.50 × 10 -9). Our findings provide new insights into the pathogenesis of schizophrenia. © 2011 Nature America, Inc. All rights reserved.


Shi Y.,Shanghai JiaoTong University | Shi Y.,Shanghai GenomePilot Institutes for Genomics and Human Health | Shi Y.,Changning Mental Health Center | Zhao H.,Shandong University | And 90 more authors.
Nature Genetics | Year: 2012

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10-8: 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS. © 2012 Nature America, Inc. All rights reserved.


Chen P.,Shanghai JiaoTong University | Pan D.,CAS Shanghai Institute of Applied Physics | Fan C.,Shanghai JiaoTong University | Fan C.,CAS Shanghai Institute of Applied Physics | And 12 more authors.
Nature Nanotechnology | Year: 2011

Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance. © 2011 Macmillan Publishers Limited. All rights reserved.


Luo C.,University of Electronic Science and Technology of China | Zhang X.,University of Electronic Science and Technology of China | Cao X.,Shanghai JiaoTong University | Gan Y.,University of Electronic Science and Technology of China | And 6 more authors.
Frontiers in Aging Neuroscience | Year: 2016

Lateralization of function is an important organization of the human brain. The distribution of intrinsic networks in the resting brain is strongly related to cognitive function, gender and age. In this study, a longitudinal design with 1 year's duration was used to evaluate the cognitive training effects on the lateralization of intrinsic networks among healthy older adults. The subjects were divided into two groups randomly: one with multi-domain cognitive training over 3 months and the other as a wait-list control group. Resting state fMRI data were acquired before training and 1 year after training. We analyzed the functional lateralization in 10 common resting state fMRI networks. We observed statically significant training effects on the lateralization of two important RSNs related to high-level cognition: right- and left- frontoparietal networks (FPNs). The lateralization of the left-FPN was retained especially well in the training group but decreased in the control group. The increased lateralization with aging was observed in the cerebellum network (CereN), in which the lateralization was significantly increased in the control group, although the same change tendency was observed in the training group. These findings indicate that the lateralization of the high-level cognitive intrinsic networks is sensitive to multi-domain cognitive training. This study provides neuroimaging evidence to support the hypothesis that cognitive training should have an advantage in preventing cognitive decline in healthy older adults. © 2016 Luo, Zhang, Cao, Gan, Li, Cheng, Cao, Jiang, Yao and Li.


Qin P.,Chinese Academy of Sciences | Li Z.,Institutes for Genomics and Human Health | Jin W.,Chinese Academy of Sciences | Lu D.,Chinese Academy of Sciences | And 6 more authors.
European Journal of Human Genetics | Year: 2014

Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ∼20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese. Based on genome-wide data, we first confirmed our previous observation of the north-south differentiation in Han Chinese population. Second, we developed a panel of 150 validated SNP AIMs to determine the northern or southern origin of each Han Chinese individual. We further evaluated the performance of our AIMs panel in association studies in simulation analysis. Our results showed that this AIMs panel had sufficient power to discern and control population stratification in Han Chinese, which could significantly reduce false-positive rates in both genome-wide association studies (GWAS) and candidate gene association studies (CGAS). We suggest this AIMs panel be genotyped and used to control and correct population stratification in the study design or data analysis of future association studies, especially in CGAS which is the most popular approach to validate previous reports on genetic associations of diseases in post-GWAS era. © 2014 Macmillan Publishers Limited All rights reserved.

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