A genome-wide association study identifies a new variant associated with word reading fluency in Chinese children

Reading disability exhibited defects in different cognitive domains, including word reading fluency, word reading accuracy, phonological awareness, rapid automatized naming and morphological awareness. To identify the genetic basis of Chinese reading disability, we conducted a genome-wide association study (GWAS) of the cognitive traits related to Chinese reading disability in 2284 unrelated Chinese children. Among the traits analyzed in the present GWAS, we detected one genome-wide significant association (p < 5 × 10⁻⁸) on word reading fluency for one SNP on 4p16.2, within EVC genes (rs6446395, p = 7.33 × 10⁻¹⁰). Rs6446395 also showed significant association with Chinese character reading accuracy (p = 2.95 × 10⁻⁴), phonological awareness (p = 7.11 × 10⁻³) and rapid automatized naming (p = 4.71 × 10⁻³), implying multiple effects of this variant. The eQTL data showed that rs6446395 affected EVC expression in the cerebellum. Gene-based analyses identified a gene (PRDM10) to be associated with word reading fluency at the genome-wide level. Our study discovered a new candidate susceptibility variant for reading ability and provided new insights into the genetics of developmental dyslexia in Chinese children.     

Identification of genetic loci associated with growth traits at weaning in yak through a genome-wide association study

A multilocus GWAS was performed to explore the genetic architecture of four growth traits in yak. In total, 354 female yaks for which measurements of body weight (BW), withers height (WH), body length (BL) and chest girth (CG) at weaning were available underwent genotyping with the Illumina BovineHD BeadChip (770K). After quality control, we retained 98 688 SNPs and 354 animals for GWAS analysis. We identified seven, 18, seven and nine SNPs (corresponding to seven, 17, seven and eight candidate genes) associated with BW, WH, BL and CG at weaning respectively. Interestingly, most of these candidate genes were reported to be involved in growth-related processes such as muscle formation, lipid deposition, feed efficiency, carcass composition and development of the central and peripheral nervous system. Our results offer novel insight into the molecular architecture underpinning yak growth traits. Further functional analyses are thus warranted to explore the molecular mechanisms whereby these genes affect these traits of interest.     

Genetic variation rs10484761 on 6p21.1 derived from a genome-wide association study is associated with gastric cancer survival in a Chinese population

A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P = 0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR = 1.41, 95% CI = 1.08–1.84 for cardia cancer and HR = 1.64, 95% CI = 1.14–2.37 for intestinal-type), tumor size ≤ 5 cm (HR = 1.41, 95% CI = 0.56–0.99), T1 depth invasion (HR = 2.34, 95% CI = 1.20–4.56), lymph node metastasis (HR = 1.51, 95% CI = 1.19–1.96), no distant metastasis (HR = 1.33, 95% CI = 1.05–1.68), TNM stage III + IV (HR = 1.50, 95% CI = 1.13–1.98), and with chemotherapy (HR = 1.53, 95% CI = 1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.     

Schizophrenia is not associated with the ERBB3 gene in a Han Chinese population sample: Results from case-control and family-based studies

ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3), encoding a receptor of neuregulin-1 (NRG1), has been considered a functional candidate gene for schizophrenia susceptibility. In order to investigate a relationship between ERBB3 gene and schizophrenia in the Chinese population, case-control and family-based studies were carried out in 470 cases matched by controls, and in 532 family trios. Our results failed to show any evidence of significant association between the ERBB3 rs2292238 polymorphism and schizophrenia.     

Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women

In the present study, we tested the association between the estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes with bone mineral density (BMD). A total of 649 healthy Chinese women, classified as pre-menopausal (N=388) and post-menopausal (N=261) groups, were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI sites. BMDs at the lumbar spine (L(1)-L(4)) and total hip were measured by dual-energy X-ray absorptiometry. For the VDR ApaI locus, AA carriers had lower spine BMD than Aa (p=0.02) and aa carriers (p<0.01) in the pre-menopausal group. For the ER-alpha gene, carriers of haplotype px had lower spine BMD than the non-carriers (p=0.03) in the pre-menopausal group. Furthermore, we observed significant interaction between the ER-alpha and VDR genes in the post-menopausal group: with AA genotype (or A allele) at the VDR ApaI locus, pX carriers had higher spine BMD than the non-carriers (p=0.02), and PX carriers had lower hip BMD than the non-carriers (p=0.04). Our data suggest that the ER-alpha and VDR genes may be associated with the BMD variation in Chinese women.     

A genome‐wide association study of coping behaviors suggests FBXO45 is associated with emotional expression

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health‐related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome‐wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi‐Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant‐level association evidence into gene‐level evidence using a gene‐based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability‐scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10^?6) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene‐based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10^?6). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene‐based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.     

A genome-wide survey of maize lipid-related genes: candidate genes mining,digital gene expression profiling and co-location with QTL for maize kernel oil

Lipids play an important role in plants due to their abundance and their extensive participation in many metabolic processes. Genes involved in lipid metabolism have been extensively studied in Arabidopsis and other plant species. In this study, a total of 1003 maize lipid-related genes were cloned and annotated, including 42 genes with experimental validation, 732 genes with full-length cDNA and protein sequences in public databases and 229 newly cloned genes. Ninety-seven maize lipid-related genes with tissue-preferential expression were discovered by in silico gene expression profiling based on 1984483 maize Expressed Sequence Tags collected from 182 cDNA libraries. Meanwhile, 70 QTL clusters for maize kernel oil were identified, covering 34.5% of the maize genome. Fifty-nine (84%) QTL clusters co-located with at least one lipid-related gene, and the total number of these genes amounted to 147. Interestingly, thirteen genes with kernel-preferential expression profiles fell within QTL clusters for maize kernel oil content. All the maize lipid-related genes identified here may provide good targets for maize kernel oil QTL cloning and thus help us to better understand the molecular mechanism of maize kernel oil accumulation.     

The C1167T polymorphism of the catalase gene and polymorphic markers D11S907 and D11S2008 located in its vicinity are associated with diabetes mellitus type 2

To study the contribution of the catalase (CAT) gene in diabetes mellitus (DM) type 2, the allele and genotype frequencies of internal (polymorphism C1167T) and two neighboring (minisatellites D11S907 and D11S2008) polymorphic markers were studied in 132 healthy individuals and 154 patients from Moscow. Allele C and genotype CC of the C1167T polymorphism proved associated with a higher risk of DM type 2. Seven D11S907 alleles containing 14 to 20 dinucleotide repeats were found. The frequencies of alleles 15 and 16 and genotype 18/20 were significantly higher and those of allele 18 and genotypes 17/18 and 18/19 were lower in patients than in controls. Eight D11S2008 alleles containing 15 to 22 tetranucleotide repeats were found. The frequencies of alleles 17 and 18 and genotype 18/20 in patients were significantly higher than in controls. An association of the three polymorphic loci and DM type 2 was suggested.     

A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population

Polyunsaturated fatty acids (PUFAs) have a major impact on human health. Recent genome-wide association studies (GWAS) have identified several genetic loci that are associated with plasma levels of n-3 and n-6 PUFAs in primarily subjects of European ancestry. However, the relevance of these findings has not been evaluated extensively in other ethnic groups. The primary aim of this study was to evaluate for genetic loci associated with n-3 and n-6 PUFAs and to validate the role of recently identified index loci using data from a Singaporean Chinese population. Using a GWAS approach, we evaluated associations with plasma concentrations of three n-3 PUFAs [alphalinolenic acid (ALA), eicosapentaenoic acid and docosahexaenoic acid], four n-6 PUFAs [linoleic acid (LA), gammalinolenic acid, dihomogammalinolenic acid (DGLA) and arachidonic acid], and estimates of delta-5 desaturase and delta-6 desaturase activities among the participants (N = 1361) of the Singaporean Chinese Health Study. Our results reveal robust genome-wide associations (p value <5 × 10⁻⁸) with ALA, all four n-6 PUFAs, and delta-6 desaturase activity at the FADS1/FADS2 locus. We further replicated the associations between common index variants at the NTAN1/PDXDC1 locus and n-6 PUFAs LA and DGLA, and between the JMJD1C locus and n-6 PUFA LA (p value between 0.0490 and 9.88 × 10⁻⁴). These associations were independent of dietary intake of PUFAs. In aggregate, we show that genetic loci that influence plasma concentrations of n-3 and n-6 PUFAs are shared across different ethnic groups.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0502-2) contains supplementary material, which is available to authorized users.     

Genomic variants associated with the number and diameter of muscle fibers in pigs as revealed by a genome-wide association study

Muscle fiber characteristics comprise a set of complex traits that influence the mea quality and lean meat production of livestock. However, the genetic and biological mechanisms regulating muscle fiber characteristics are largely unknown in pigs. Based on a genome-wide association study (GWAS) performed on 421 Large White × Min pig F2 individuals presenting well-characterized phenotypes, this work aimed to detect genome variations and candidate genes for five muscle fiber characteristics: percentage of type I fibers (FIB1P), percentage of type IIA fibers (FIB2AP), percentage of type IIB fibers (FIB2BP), diameter of muscle fibers (DIAMF) and number of muscle fibers per unit area (NUMMF). The GWAS used the Illumina Porcine SNP60K genotypic data, which were analyzed by a mixed model. Seven and 10 single nucleotide polymorphisms (SNPs) were significantly associated with DIAMF and NUMMF, respectively (P < 1.10E-06); no SNP was significantly associated with FIB1P, FIB2AP or FIB2B. For DIAMF, the significant SNPs on chromosome 4 were located in the previously reported quantitative trait loci (QTL) interval. Because the significant SNPs on chromosome 6 were not mapped in the previously reported QTL interval, a putative novel QTL was suggested for this locus. None of the previously reported QTL intervals on chromosomes 6 and 14 harbored significant SNPs for NUMMF; thus, new potential QTLs on these two chromosomes are suggested in the present work. The most significant SNPs associated with DIAMF (ALGA0025682) and NUMMF (MARC0046984) explained 12.02% and 11.59% of the phenotypic variation of these traits, respectively. In addition, both SNPs were validated as associated with DIAMF and NUMMF in Beijing Black pigs (P < 0.01). Some candidate genes or non-coding RNAs, such as solute carrier family 44 member 5 and miR-124a-1 for DIAMF, and coiled-coil serine rich protein 2 for NUMMF, were identified based on their close location to the significant SNPs. This study revealed some genome-wide association variants for muscle fiber characteristics, and it provides valuable information to discover the genetic mechanisms controlling these traits in pigs.     

Alpha-defensin DEFA1A3 gene copy number variation in Asians and its genetic association study in Chinese systemic lupus erythematosus patients

Neutrophil extracellular traps (NETs) were closely associated with activation of type I interferon (IFN) pathway in systemic lupus erythematosus (SLE). We aimed to study the genetic basis of NETs-DEFA1A3 copy number variations (CNV) in SLE and HapMap CHB + JPT populations by quantitative real-time PCR and whole genome sequences data. DEFA1A3 CNs did not differ significantly between SLE patients and controls. DEFA1A3 CNs ranged from 3 to 11 in CHB and 4 to 16 in JPT. The median of DEFA1A3 CNV of CHB (6 copies) was significantly lower than that of JPT (9 copies). Associations of genotype of tag SNP rs2738113 with DEFA1A3 CNs and mRNA expression of IFNα were observed in CHB and JPT populations. Our data provided a genetic reference of DEFA1A3 CNV for further studies and suggested that the genetic pathogenesis of NETs, as well as DEFA1A3 in SLE should be further evaluated, specially in different populations.     

Habitat availability and gene flow influence diverging local population trajectories under scenarios of climate change: a place‐based approach

Ecological niche theory holds that species distributions are shaped by a large and complex suite of interacting factors. Species distribution models (SDMs) are increasingly used to describe species’ niches and predict the effects of future environmental change, including climate change. Currently, SDMs often fail to capture the complexity of species’ niches, resulting in predictions that are generally limited to climate‐occupancy interactions. Here, we explore the potential impact of climate change on the American pika using a replicated place‐based approach that incorporates climate, gene flow, habitat configuration, and microhabitat complexity into SDMs. Using contemporary presence–absence data from occupancy surveys, genetic data to infer connectivity between habitat patches, and 21 environmental niche variables, we built separate SDMs for pika populations inhabiting eight US National Park Service units representing the habitat and climatic breadth of the species across the western United States. We then predicted occurrence probability under current (1981–2010) and three future time periods (out to 2100). Occurrence probabilities and the relative importance of predictor variables varied widely among study areas, revealing important local‐scale differences in the realized niche of the American pika. This variation resulted in diverse and – in some cases – highly divergent future potential occupancy patterns for pikas, ranging from complete extirpation in some study areas to stable occupancy patterns in others. Habitat composition and connectivity, which are rarely incorporated in SDM projections, were influential in predicting pika occupancy in all study areas and frequently outranked climate variables. Our findings illustrate the importance of a place‐based approach to species distribution modeling that includes fine‐scale factors when assessing current and future climate impacts on species’ distributions, especially when predictions are intended to manage and conserve species of concern within individual protected areas.