Identification of genomewide single-nucleotide polymorphisms associated with presummer, summer and autumn bolls in upland cotton

Presummer, summer, and autumn bolls (PSB, SB and AB, respectively) in cotton are related to both maturity and yield. Therefore, studying their genetic basis is important for breeding purposes. In this study, we developed an association analysis panel consisting of 169 upland cotton accessions. The panel was phenotyped for PSB, SB and AB across four environments and genotyped using a Cotton SNP80K array. Single-nucleotide polymorphisms (SNPs) associated with these three traits were identified by a genomewide association study. A total of 53,848 high-quality SNPs were screened, and 91 significant trait-associated SNPs were detected. Of the 91 SNPs 33 were associated with PSB, 21 with SB and 37 with AB. Three SNPs for PSB (TM10410, TM13158 and TM21762) and five for AB (TM13730, TM13733, TM13834, TM29666 and TM43214) were repeatedly detected in two environments or by two methods. These eight SNPs exhibited high phenotypic variation of more than 10%, thus allowing their use formarker-assisted selection. The candidate genes for target traits were also identified. These findings provide a theoretical basis for the improvement of early maturity and yield in cotton breeding programmes.

Genetic underpinnings of lung function and COPD

Spirometry based measurement of lung function is a global initiative for chronic obstructive lung disease (GOLD) standard to diagnose chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality worldwide. Theenvironmental and behavioural risk factors for COPD includes tobacco smoking, air pollutants and biomass fuel exposure, which can induce one or more abnormal lung function patterns. While smoking remains the primary risk factor, only 15–20% smokers develop COPD, indicating that the genetic factors are also likely to play a role. According to the study of Global Burden of Disease 2015, ∼174 million people across the world have COPD. From a comprehensive literature search conducted using the ‘PubMed’ and ‘GWAS Catalogue’ databases, and reviewing the literature available, only a limited number of studies were identified which hadattempted to investigate the genetics of COPD and lung volumes, implying a huge research gap. With the advent of genomewide association studies several genetic variants linked to lung function and COPD, like HHIP, HTR4, ADAM19 and GSTCD etc., have been found and validated in different population groups, suggesting their potential role in determining lung volume and risk for COPD. This article aims at reviewing the present knowledge of the genetics of lung function and COPD

Genomewide association study for C-reactive protein in Indians replicates known associations of common variants

Elevated C-reactive protein (CRP) serves as an independent biomarker for acute and chronic inflammation, and is also associated with metabolic diseases. Genomewide loci regulating CRP level in Indian population, a high-risk group for metabolic illness, is unexplored. Therefore, we aimed to discover common polymorphisms associated with plasma CRP level in 4493 Indians of Indo-European origin using genomewide association study. Genomewide strong associations of two known intronic variants in hepatocyte nuclear factor-1 α gene (HNF1A)were identified among Indian subjects. We also detected prior associations of several variants in/near metabolic and inflammatory process genes: APOC1, LEPR, CRP, HNF4A, IL6R and APOE with modest associations. This study confirms that Indians from Indo-European origin display similar core universal genetic factors for CRP levels.

Genomewide association study of C-peptide surfaces key regulatory genes in IndiansC

Insulin is a commonly used measure of pancreatic β-cell function but exhibits a short half-life in the human body. During biosynthesis, insulin release is accompanied by C-peptide at an equimolar concentration which has a much higher plasma half-life and is therefore projected as a precise measure of β-cell activity than insulin. Despite this, genetic studies of metabolic traits haveneglected the regulatory potential of C-peptide for therapeutic intervention of type-2 diabetes. The present study is aimed to search genomewide variants governing C-peptide levels in genetically diverse and high risk population for metabolic diseases—Indians. We performed whole genome genotyping in 877 healthy Indians of Indo-European origin followed by replication of variants with P ≤ 1 × 10−3 in an independent sample-set of 1829 Indians. Lead-associated signals were also tested in-silico in 773 Hispanics. To secure biological rationale for observed association, we further carried out DNA methylation quantitative trait loci analysis in 233 Indians and publicly available regulatory data was mined. We discovered novel lncRNA gene AC073333.8 with the strongest association with C-peptide levels in Indians that however missed genomewide significance. Also, noncoding genes, RP1-209A6.1 and RPS3AP5; protein gene regulators, ZNF831 and ETS2; and solute carrier protein gene SLC15A5 retained robust association with C-peptide after meta-analysis. Integration of methylation data revealed ETS2 and ZNF831 single-nucleotide polymorphisms as significant meth-QTLs in Indians. All genes showed reasonable expression in the human lung, signifying alternate important organs for C-peptide biology. Our findings mirror polygenic nature of C-peptide where multiple small-effect size variants in the regulatory genome principally govern the trait biology.

Advances in the genetics of moyamoya disease / 国际脑血管病杂志

Moyamoya disease is a rare cerebrovascular disease.Its incidence is higher in the East Asia.The pathogenesis of MMD remains unclear at present,but the epidemiological research both at home and abroad suggests that the genetic factors play an important role in the onset of MMD.This article briefly reviews the recent progress in research on MMD related genes.

Genome-wide Association Study Identification of a New Genetic Locus with Susceptibility to Osteoporotic Fracture in the Korean Population

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genomewide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=1.27x10(-5)) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.

KARE Genomewide Association Study of Blood Pressure Using Imputed SNPs

The imputation of untyped SNPs enables researchers to validate association findings across SNP arrays and also enables them to test a large number of SNPs to reveal the fine structure of the association peak, facilitating interpretation of the results and the location of causal polymorphisms. In this study, we applied the imputation method to a genomewide association study and recapitulated the previously associated gene loci of blood pressure traits in Korean cohorts. A total of 1,827,004 SNPs were imputed by the IMPUTE program, and we conducted a genomewide association study for systolic and diastolic blood pressure. While no SNPs passed the Bonferroni correction p-value (p=2.74x10-8 for 1,827,004 SNPs), 12 novel loci for systolic blood pressure and 16 novel loci for diastolic blood pressure were detected by imputed SNPs, with 10-5

Genome-Wide Association Analyses on Blood Pressure Using Three Different Phenotype Definitions

Hypertension is the most prevalent disease worldwide and is itself a risk factor for cerebral, cardiac, and renal diseases. The inconsistency of candidate genes suggested by previous genomewide association studies (GWASs) may be due to not only differences in study design and genetic or environmental background but also the difference in the power of analysis between continuous traits and discrete traits. We analyzed 352,228 single nucleotide polymorphisms (SNPs) in 8842 unrelated Koreans obtained from Ansan and Ansung cohorts. We performed a series of GWA analyses using three different phenotype models; young hypertensive cases (278 subjects) versus elderly normotensive controls (680 subjects); the upper 25% (2211 hypertensive cases) versus the lower 25% of the SBP distribution (2211 hypotensive controls); and finally SBP and DBP as continuous traits (8842 subjects). The numbers of young hypertensive cases and elderly normotensive controls were not large enough to achieve genomewide significance. The model comparing the upper 25% subjects to the lower 25% of subjects showed a power that was approximate to that of QTL analysis. Two neighboring SNPs of the ATP2B1 gene, rs17249754 (SBP, p=2.53-10; DBP, p=1.28x10-8) and rs7136259 (SBP, p=1.30x10-9; DBP, p=6.41x10-8), were associated with both SBP and DBP. Interestingly, a SNP of the RPL6 gene, rs11066280, revealed a significant genomewide association with SBP in men only (p=3.85x10-8), and four SNPs located near the MAN2A1 gene showed a strong association with DBP only in elderly men aged 60-70 years (e.g., rs6421827, p=4.86x10-8). However, we did not observe any gene variant attaining genome-wide significance consistently in the three phenotype models except for the ATP2B1 gene variants. In general, the association signal with blood pressure was stronger in women than in men. Genes identified in GWASs are expected to open the way for prevention, early diagnosis, and personalized treatment of hypertension.