Genome-Wide Association Study Identified Copy Number Variants Important for Appendicular Lean Mass

BackgroundMultiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC.MethodsA genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform. After 16 principal component corrections, univariate and multivariate segmentations followed by association testing were performed on 1830 samples that passed quality assurance tests.ResultsA rare CNV region (CNVR) at chromosome 14q11 (OR=1.92 (95% CI 1.59 to 2.32), p=2.7e-12) encompassing CHD8, and common CNVR at chromosomes 3q13.12 (OR=1.54 (95% CI 1.33 to 1.77), p=2.9e-9) and 12p12.3 (OR=1.69 (95% CI 1.41 to 2.01), p=2.8e-9) encompassing CD47 and RERG/ARHGDIB, respectively, were significantly associated with CRC risk. CNV loci were validated in an independent replication panel using an optimised copy number assay. Whole-genome expression data in matched tumours of a subset of cases demonstrated that copy number loss at CHD8 was significantly associated with dysregulation of several genes that perturb the Wnt, TP53 and inflammatory pathways.ConclusionsA rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis.

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Genome-wide association study between copy number variants and hoof health traits in Holstein dairy cattle

Journal of Dairy Science ◽

10.3168/jds.2020-19879 ◽

2021 ◽

Author(s):

Adrien M. Butty ◽

Tatiane C.S. Chud ◽

Diercles F. Cardoso ◽

Lucas S.F. Lopes ◽

Filippo Miglior ◽

...

Keyword(s):

Dairy Cattle ◽

Association Study ◽

Copy Number ◽

Genome Wide Association Study ◽

Copy Number Variants ◽

Genome Wide Association ◽

Genome Wide

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Genome-wide association study of appendicular lean mass in UK Biobank cohort

10.1101/643536 ◽

2019 ◽

Author(s):

Yu-Fang Pei ◽

Yao-Zhong Liu ◽

Xiao-Lin Yang ◽

Hong Zhang ◽

Gui-Juan Feng ◽

...

Keyword(s):

Association Study ◽

Lean Mass ◽

Genetic Basis ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Phenotypic Variance ◽

Uk Biobank ◽

Appendicular Lean Mass ◽

Gene Sets ◽

Genome Wide

AbstractLean body mass (LBM), an important physiological measure, has a strong genetic determination. To clarify its genetic basis, a large-scale genome-wide association study (GWAS) of appendicular lean mass (ALM) was conducted in 450,580 UK Biobank subjects. A total of 717 variants (p<5×10−9) from 561 loci were identified, which were replicated across genders (achieving p<5×10−5 in both genders). The identified variants explained ~11% phenotypic variance, accounting for one quarter of the total ~40% GWAS-attributable heritability. The identified variants were enriched in gene sets related to musculoskeletal and connective tissue development. Of interest are several genes, including ADAMTS3, PAM, SMAD3 and MEF2C, that either contain multiple significant variants or serve as the hub genes of the associated gene sets. Polygenic score prediction based on the associated variants was able to distinguish subjects of high from low ALM. Overall, our results offered significant findings on the genetic basis of lean mass through an extraordinarily large sample GWAS. The findings are important to not only lean mass per se but also other complex diseases, such as type 2 diabetes and fracture, as our Mendelian randomization analysis showed that ALM is a protective factor for these two diseases.

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Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males

Bone ◽

10.1016/j.bone.2012.08.127 ◽

2012 ◽

Vol 51 (6) ◽

pp. 1000-1007 ◽

Cited By ~ 10

Author(s):

Yingying Han ◽

Yufang Pei ◽

Yaozhong Liu ◽

Lei Zhang ◽

Shuyan Wu ◽

...

Keyword(s):

Compressive Strength ◽

Fatty Acid ◽

Association Study ◽

Lean Mass ◽

Genome Wide Association Study ◽

Fatty Acid Desaturase ◽

Genome Wide Association ◽

Strength Index ◽

Appendicular Lean Mass ◽

Genome Wide

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A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

Cytogenetic and Genome Research ◽

10.1159/000448558 ◽

2016 ◽

Vol 149 (3) ◽

pp. 156-164 ◽

Cited By ~ 2

Author(s):

Yadav Sapkota ◽

Ashok Narasimhan ◽

Mahalakshmi Kumaran ◽

Badan S. Sehrawat ◽

Sambasivarao Damaraju

Keyword(s):

Breast Cancer ◽

Association Study ◽

Copy Number ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Frequency Effect ◽

Potential Candidate ◽

Disease Etiology ◽

Genome Wide ◽

A Genome

Breast cancer (BC) predisposition in populations arises from both genetic and nongenetic risk factors. Structural variations such as copy number variations (CNVs) are heritable determinants for disease susceptibility. The primary objectives of this study are (1) to identify CNVs associated with sporadic BC using a genome-wide association study (GWAS) design; (2) to utilize 2 distinct CNV calling algorithms to identify concordant CNVs as a strategy to reduce false positive associations in the hypothesis-generating GWAS discovery phase, and (3) to identify potential candidate CNVs for follow-up replication studies. We used Affymetrix SNP Array 6.0 data profiled on Caucasian subjects (422 cases/348 controls) to call CNVs using algorithms implemented in Nexus Copy Number and Partek Genomics Suite software. Nexus algorithm identified CNVs associated with BC (731 autosomal CNVs with >5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication.

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