scholarly journals BMI prediction within a Korean population

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3510 ◽  
Author(s):  
Jin Sol Lee ◽  
Hyun Sub Cheong ◽  
Hyoung-Doo Shin
Keyword(s):  
Cross Validation ◽  
Genome Wide Association Study ◽  
Korean Population ◽  
Risk Scores ◽  
Link Type ◽  
Genome Wide ◽  
Clinical Trait ◽  
Validation Set ◽  
Fold Cross Validation

Background Body Mass Index (BMI) is widely regarded as an important clinical trait for obesity and other diseases such as Type 2 diabetes, coronary heart disease, and osteoarthritis. Methods This study uses 6,011 samples of genotype data from ethnic Korean subjects. The data was retrieved from the Korea Association Resource. To identify the BMI-related markers within the Korean population, we collected genome-wide association study (GWAS) markers using a GWAS catalog and also obtained other markers from nearby regions. Of the total 6,011 samples, 5,410 subjects were used as part of a single nucleotide polymorphism (SNP) selection set in order to identify the overlapping BMI-associated SNPs within a 10-fold cross validation. Results We selected nine SNPs (rs12566985 (FPGT-TNNI3K), rs6545809 (ADCY3), rs2943634 (located near LOC646736), rs734597 (located near TFAP2B), rs11030104 (BDNF), rs7988412 (GTF3A), rs2241423 (MAP2K5), rs7202116 (FTO), and rs6567160 (located near LOC105372152) to assist in BMI prediction. The calculated weighted genetic risk scores based on the selected 9 SNPs within the SNP selection set were applied to the final validation set consisting of 601 samples. Our results showed upward trends in the BMI values (P < 0.0001) within the 10-fold cross validation process for R2 > 0.22. These trends were also observed within the validation set for all subjects, as well as within the validation sets divided by gender (P < 0.0001, R2 > 0.46). Discussion The set of nine SNPs identified in this study may be useful for prospective predictions of BMI.

scholarly journals Prediction of cholesterol ratios within a Korean population

2018 ◽  
Vol 5 (1) ◽  
pp. 171204
Author(s):  
Jin Sol Lee ◽  
Hyun Sub Cheong ◽  
Hyoung Doo Shin
Keyword(s):  
Genetic Risk ◽  
Cross Validation ◽  
Density Lipoprotein ◽  
Risk Scores ◽  
Genotype Data ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Regression Slopes ◽  
Validation Set ◽  
Fold Cross Validation

Cholesterol ratios (total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c) and triglyceride (TG)/HDL-c) have been suggested as better indicators to predict various clinical features such as insulin resistance and heart disease. Therefore, we aimed to build a single nucleotide polymorphism (SNP) set to predict constitutional lipid metabolism. The genotype data of 7795 samples were obtained from the Korea Association Resource. Among the total of 7795 samples, 7016 subjects were used to perform 10-fold cross-validation. We selected the SNPs that showed significance constantly throughout all 10 cross-validation sets; another 779 samples were used as the final validation set. After performing the 10-fold cross-validation, the six SNPs ( rs4420638 ( APOC1 ), rs12421652 ( BUD13 ) , rs17411126 ( LPL ) , rs6589566 ( ZPR1 ) , rs16940212 ( LOC101928635 ) and rs10852765 ( ABCA8 )) were finally selected for predicting cholesterol ratios. The weighted genetic risk scores (wGRS) were calculated based on the regression slopes of the six selected SNPs. Our results showed upward trends of wGRS for both the TC/HDL-c and TG/HDL-c ratios within the 10-fold cross-validation. Similarly, the wGRS of the six SNPs also showed upward trends in analyses using the SNP selection set and final validation set. The selected six SNPs can be used to explain both the TC/HDL-c and TG/HDL-c ratios. Our results may be useful for the prospective predictions of cholesterol-related diseases.

The First Genome-Wide Association Study (GWAS) for Type 2 Diabetes in Youth from the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1703-P ◽  
Author(s):  
SHYLAJA SRINIVASAN ◽  
JENNIFER TODD ◽  
LING CHEN ◽  
JASMIN DIVERS ◽  
SAM GIDDING ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Diabetes Genetics ◽  
Diabetes In Youth

scholarly journals Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
José Jaime Martínez-Magaña ◽  
Alma Delia Genis-Mendoza ◽  
Jorge Ameth Villatoro Velázquez ◽  
Marycarmen Bustos-Gamiño ◽  
Isela Esther Juárez-Rojop ◽  
...  
Keyword(s):  
Substance Use ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Logistic Models ◽  
Genome Wide Association ◽  
Risk Scores ◽  
Multinomial Models ◽  
Gamma Receptor ◽  
Genome Wide ◽  
A Genome

AbstractThe combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e−05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

scholarly journals A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Juliette Coignard ◽  
◽  
Michael Lush ◽  
Jonathan Beesley ◽  
Tracy A. O’Mara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Genome Wide Association Study ◽  
Brca2 Mutation ◽  
Risk Scores ◽  
Genetic Modifiers ◽  
Mutation Carriers ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
Brca1 Brca2

AbstractBreast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

scholarly journals Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

2021 ◽  
Vol 118 (12) ◽  
pp. e2005753118
Author(s):  
Aditya Ambati ◽  
Ryan Hillary ◽  
Smaranda Leu-Semenescu ◽  
Hanna M. Ollila ◽  
Ling Lin ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Genome Wide Association Study ◽  
Perinatal Outcomes ◽  
Case Control ◽  
Risk Scores ◽  
Circadian Regulation ◽  
Genetic Associations ◽  
Imaging Studies ◽  
Genome Wide

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case−control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10−9) within the 3′region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10−22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

scholarly journals Genome-Wide Association Study Identifies an Immune-Related Etiology for Severe Aplastic Anemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1224-1224
Author(s):  
Sharon A. Savage ◽  
Mathias Viard ◽  
Weiyin Zhou ◽  
Meredith Yeager ◽  
Shengchao Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Association Study ◽  
Research Funding ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Class I ◽  
Severe Aplastic Anemia ◽  
Genome Wide ◽  
Validation Set

Introduction. Acquired severe aplastic anemia (SAA) is a life-threatening disorder characterized by severe progressive pancytopenia and hypocellular bone marrow. The etiology of acquired SAA is not understood but believed to be related to abnormal immune responses to environmental exposures. We conducted a genome-wide association study (GWAS) to identify common germline variants associated with SAA. Methods. We identified 895 patients with SAA who underwent related or unrelated hematopoietic cell transplant (HCT) with clinical data and pre-HCT blood samples available in the Center for International Blood and Marrow Transplant Research (CIBMTR) database and biorepository. Pre-HCT DNA was extracted from blood of patients with SAA and genome-wide genotyping was conducted using the Illumina OmniExpress array. We excluded 93 inherited bone marrow failure cases. The SAA cases were grouped cases into discovery and validation sets based on time of batch sample receipt. Analyses were limited to patients of European ancestry based on principal component analyses to minimize the potential effect of population stratification. Controls were genomically matched and selected from previously scanned cancer-free subjects at the Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, NCI. The final analysis included 534 acquired SAA cases (359 in the discovery set and 175 in the validation set), and 2,455 controls (1,396 in the discovery set, and 1,059 in the validation set). Results. Patients with SAA in this study received HCT between 1989-2015 at a median age of 21 years, 56% were male, and the median time between SAA diagnosis and HCT was 11 months. Strong genome-wide association signals were identified across the human leukocyte antigen (HLA) genes encoded at the major histocompatibility complex (MHC) on chromosome 6p21 (Figure 1). The top SNP was located in the P4 binding pocket of the HLA class II gene HLA-DPB1(rs1042151A>G, p.Met105Val, pooled-odds ratio [OR]=1.75, 95% confidence interval [CI]=1.50-2.03, p=1.94x10-13). The expression of HLA-DP in CD19+ cells from 175 healthy donors was significantly different by rs1042151 A>G genotype (p=2.04x10-6) (Figure 2). A second SNP near HLA-B, rs28367832G>A, also reached genome-wide significance (pooled-OR=1.49, 95% CI=1.22-1.78, p=7.27x10-9). Copy-number variant analysis and next generation sequencing also identified somatic, clonal copy-neutral loss-of-heterozygosity affecting class I HLA genes in 8.6% of the SAA cases and none of the controls. Conclusion. This SAA GWAS identified strong association signals between common germline genetic variants in HLA class I and II genes and SAA. The main SNP is associated with changes in HLA-DP expression suggesting a key role for this locus in SAA etiology. This study adds further evidence to the connection between SAA and immune dysregulation. Disclosures Cerhan: Janssen: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; Celgene: Research Funding. Lee:Incyte: Research Funding; Syndax: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Kadmon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; AstraZeneca: Research Funding.

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