scholarly journals Clustering by phenotype and genome-wide association study in autism

2019 ◽  
Author(s):  
Akira Narita ◽  
Masato Nagai ◽  
Satoshi Mizuno ◽  
Soichi Ogishima ◽  
Gen Tamiya ◽  
...  
Keyword(s):  
Association Study ◽  
Complex Disease ◽  
Genome Wide Association Study ◽  
Autism Spectrum ◽  
Genome Wide Association ◽  
Second Step ◽  
Cluster Number ◽  
Genome Wide ◽  
Preliminary Study ◽  
Chromosomal Loci

AbstractBackgroundAutism spectrum disorder (ASD) has phenotypically and genetically heterogeneous characteristics. A simulation study demonstrated that attempts to categorize patients with a complex disease into more homogeneous subgroups could have more power to elucidate hidden heritability.MethodsWe conducted cluster analyses using the k-means algorithm with a cluster number of 15 based on phenotypic variables from the Simons Simplex Collection (SSC). As a preliminary study, we conducted a conventional genome-wide association study (GWAS) with a dataset of 597 ASD cases and 370 controls. In the second step, we divided cases based on the clustering results and conducted GWAS in each of the subgroups vs controls (cluster-based GWAS). We also conducted cluster-based GWAS on another SSC dataset of 712 probands and 354 controls in the replication stage.ResultsIn the preliminary study, we observed no significant associations. In the second step of cluster-based GWASs, we identified 65 chromosomal loci, which included 30 intragenic loci located in 21 genes and 35 intergenic loci that satisfied the threshold of P<5.0×10−8. Some of these loci were located within or near previously reported candidate genes for ASD: CDH5, CNTN5, CNTNAP5, DNAH17, DPP10, DSCAM, FOXK1, GABBR2, GRIN2A5, ITPR1, NTM, SDK1, SNCA and SRRM4. Of these 65 significant chromosomal loci, rs11064685 located within the SRRM4 gene had a significantly different distribution in the cases vs. controls in the replication cohort.ConclusionsThese findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies. Further cluster validation and replication studies are warranted in larger cohorts.

Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations

2015 ◽  
Vol 9 (3) ◽  
pp. 340-349 ◽  
Author(s):  
Xiaoxi Liu ◽  
Takafumi Shimada ◽  
Takeshi Otowa ◽  
Yu-Yu Wu ◽  
Yoshiya Kawamura ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Association Study ◽  
Genome Wide Association Study ◽  
East Asian ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Genome Wide Association ◽  
Asian Populations ◽  
Genome Wide

scholarly journals Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

2021 ◽  
Author(s):  
Tarunveer S Ahluwalia ◽  
Bram P Prins ◽  
Mohammadreza Abdollahi ◽  
Nicola J Armstrong ◽  
Stella Aslibekyan ◽  
...  
Keyword(s):  
Association Study ◽  
Interleukin 6 ◽  
Fixed Effects ◽  
Complex Disease ◽  
Genome Wide Association Study ◽  
Heritability Estimate ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
Increased Risk

Abstract Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

scholarly journals A sex-stratified genome-wide association study of tuberculosis using a multi-ethnic genotyping array

2018 ◽  
Author(s):  
Haiko Schurz ◽  
Craig J Kinnear ◽  
Chris Gignoux ◽  
Genevieve Wojcik ◽  
Paul D van Helden ◽  
...  
Keyword(s):  
Association Study ◽  
X Chromosome ◽  
Complex Disease ◽  
Genome Wide Association Study ◽  
Interaction Analysis ◽  
Genome Wide Association ◽  
Genotyping Array ◽  
Association Testing ◽  
Genome Wide ◽  
A Genome

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis, is a complex disease with a known human genetic component. Males seem to be more affected than females and in most countries the TB notification rate is twice as high in males as in females. While socio-economic status, behaviour and sex hormones influence the male bias they do not fully account for it. Males have only one copy of the X chromosome, while diploid females are subject to X chromosome inactivation. In addition, the X chromosome codes for many immune-related genes, supporting the hypothesis that X-linked genes could contribute to TB susceptibility in a sex-biased manner. We report the first TB susceptibility genome-wide association study (GWAS) with a specific focus on sex-stratified autosomal analysis and the X chromosome. Individuals from an admixed South African population were genotyped using the Illumina Multi Ethnic Genotyping Array, specifically designed as a suitable platform for diverse and admixed populations. Association testing was done on the autosome and X chromosome in a sex stratified and combined manner. SNP association testing was not statistically significant using a stringent cut-off for significance but revealed likely candidate genes that warrant further investigation. A genome wide interaction analysis detected 16 significant interactions. Finally, the results highlight the importance of sex-stratified analysis as strong sex-specific effects were identified on both the autosome and X chromosome.

scholarly journals Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138695 ◽  
Author(s):  
Po-Hsiu Kuo ◽  
Li-Chung Chuang ◽  
Mei-Hsin Su ◽  
Chia-Hsiang Chen ◽  
Chien-Hsiun Chen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Genome Wide Association ◽  
Han Population ◽  
Genome Wide
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