Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies

現在，統合失調症を含んだcommon disease のゲノムワイド相関研究(genome-wide association study:GWAS) が盛んに行われている．統合失調症に関しては，七つのGWAS が施行された．その後，さらに対象を増やしたGWAS のfollow-up 研究も行われた．これらのGWAS とfollow-up により，統合失調症と以下の遺伝子の相関が検出された：1) 12 番染色体上のCACNA1C 遺伝子(P＝1.2×10-8)，2) 2 番染色体上のZNF804A 遺伝子(P＝4.1×10-13)．1) は対象数57,213 人，2) は対象数59,949 人で確認された．今後は，GWAS とfollow-up で得られた所見を基に，さらなる研究が進められていくと思われる．

Genome-wide Association Study

Genetic Association

10.4264/numa.73.106

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Supplementary Figure 1 from Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry

Alexandra R. Harris Gatikrushna Panigrahi Huaitian Liu Vishal N. Kopardé Maeve Bailey‐Whyte

<p>Supplemental Figure 1. Quantified genetic ancestry in TCGA participants by self-reported race. Using published ancestry annotations from Carrot-Zhang et al1, quantified genetic ancestry was compared to self-reported race (SRR). For 111/112 TCGA samples used in our study, genetic ancestry consensus was concordant with SRR. Genetic ancestry consensus classification of African or admixed African ancestry captured 100% of TCGA participants who self-identified as “Black or African American”. Genetic ancestry consensus classification of EUR ancestry captured 98.7% of TCGA participants who self-identified as “White”; in one case, a participant that self-identified as White demonstrated a higher proportion of admixed American genetic ancestry. Among TCGA participants who self-identified as Black or African American, the average percentage of African ancestry was 83.2%, which is comparable to the quantified genetic ancestry estimates for the human cell lines used in this study that were classified as African American-derived (average African ancestry of 79.5%). Among TCGA participants who self-identified as White, the average percentage of European ancestry was 96.7%, which is comparable to the quantified genetic ancestry estimates for the human cell lines used in this study that were classified as European American-derived (average European ancestry of 93.0%).</p>

Genetic genealogy

Genetic admixture

Ancestry-informative marker

White (mutation)

10.1158/2767-9764.24250522

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Evaluating three strategies of genome‐wide association analysis for integrating data from multiple populations

Animal Genetics (2024)

Zhanming Zhong Guangzhen Li Zhiting Xu Haonan Zeng Jinyan Teng

Abstract In livestock, genome‐wide association studies (GWAS) are usually conducted in a single population (single‐GWAS) with limited sample size and detection power. To enhance the detection power of GWAS, meta‐analysis of GWAS (meta‐GWAS) and mega‐analysis of GWAS (mega‐GWAS) have been proposed to integrate data from multiple populations at the level of summary statistics or individual data, respectively. However, there is a lack of comparison for these different strategies, which makes it difficult to guide the best practice of GWAS integrating data from multiple study populations. To maximize the comparison of different association analysis strategies across multiple populations, we conducted single‐GWAS, meta‐GWAS, and mega‐GWAS for the backfat thickness of 100 kg (BFT_100) and days to 100 kg (DAYS_100) within each of the three commercial pig breeds (Duroc, Yorkshire, and Landrace). Based on controlling the genome inflation factor to one, we calculated corrected p ‐values ( p C ). In Yorkshire, with the largest sample size, mega‐GWAS, meta‐GWAS and single‐GWAS detected 149, 38 and 20 significant SNPs ( p C < 1E‐5) associated with BFT_100, as well as 26, four, and one QTL, respectively. Among them, p C of SNPs from mega‐GWAS was the lowest, followed by meta‐GWAS and single‐GWAS. The correlation of p C among the three GWAS strategies ranged from 0.60 to 0.75 and the correlation of SNP effect values between meta‐GWAS and mega‐GWAS was 0.74, all showing good agreement. Collectively, even though there are differences in the integration of individual data or summary statistics, integrating data from multiple populations is an effective means of genetic argument for complex traits, especially mega‐GWAS versus single‐GWAS.

Genome-wide Association Study

Genetic Association

SNP

10.1111/age.13394

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Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses

Alcoholism Clinical and Experimental Research (2015)

Amy Hart Henry R. Kranzler

Background Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) have improved the detection of specific loci associated with complex traits, including AD. However, findings from GWAS explain only a small proportion of phenotypic variance, and alternative methods have been proposed to investigate the associations that do not meet strict genome-wide significance criteria. Methods This review summarizes all published AD GWAS and post-GWAS analyses that have sought to exploit GWAS data to identify AD-associated loci. Results Findings from AD GWAS have been largely inconsistent, with the exception of variants encoding the alcohol-metabolizing enzymes. Analyses of GWAS data that go beyond standard association testing have demonstrated the polygenic nature of AD and the large contribution of common variants to risk, nominating novel genes and pathways for AD susceptibility. Conclusions Findings from AD GWAS and post-GWAS analyses have greatly increased our understanding of the genetic etiology of AD. However, it is clear that larger samples will be necessary to detect loci in addition to those that encode alcohol-metabolizing enzymes, which may only be possible through consortium-based efforts. Post-GWAS approaches to studying the genetic influences on AD are increasingly common and could greatly increase our knowledge of both the genetic architecture of AD and the specific genes and pathways that influence risk.

Genome-wide Association Study

Genetic Association

Missing heritability problem

10.1111/acer.12792

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A genome-wide association study (GWAS) for myopia susceptibility in chicks

Investigative Ophthalmology & Visual Science (2017)

Yu Huang Chea‐su Kee Shea Ping Yip Jeremy A. Guggenheim

Genome-wide Association Study

Genetic Association

Association (psychology)

Source

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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Nature Genetics (2022)

Kazuyoshi Ishigaki Saori Sakaue Chikashi Terao Yang Luo Kyuto Sonehara

Genome-wide Association Study

Genetic genealogy

Genetic Association

Genetic architecture

1000 Genomes Project

10.1038/s41588-022-01213-w

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Citations (181)

Trans-ancestry genome-wide association study identifies novel genetic mechanisms in rheumatoid arthritis

medRxiv (Cold Spring Harbor Laboratory) (2021)

Kazuyoshi Ishigaki Saori Sakaue Chikashi Terao Yang Luo Kyuto Sonehara

Abstract Trans-ancestry genetic research promises to improve power to detect genetic signals, fine-mapping resolution, and performances of polygenic risk score (PRS). We here present a large-scale genome-wide association study (GWAS) of rheumatoid arthritis (RA) which includes 276,020 samples of five ancestral groups. We conducted a trans-ancestry meta-analysis and identified 124 loci ( P < 5 × 10 -8 ), of which 34 were novel. Candidate genes at the novel loci suggested essential roles of the immune system (e.g., TNIP2 and TNFRSF11A ) and joint tissues (e.g., WISP1 ) in RA etiology. Trans-ancestry fine mapping identified putatively causal variants with biological insights (e.g., LEF1 ). Moreover, PRS based on trans-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between European and East Asian populations. Our study provides multiple insights into the etiology of RA and improves genetic predictability of RA.

Genome-wide Association Study

Genetic Association

Genetic genealogy

Genetic architecture

Candidate gene

10.1101/2021.12.01.21267132

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Citations (14)

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Xiangrui Meng Georgina Navoly Olga Giannakopoulou Daniel F. Levey Dóra Koller

Abstract Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with ≤5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

Genome-wide Association Study

Genetic genealogy

Genetic Association

Ancestry-informative marker

1000 Genomes Project

10.1101/2022.07.20.500802

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Genome-wide studies of primary open-angle glaucoma

Russian Annals of Ophthalmology (2020)

Natalya Eliseeva Mikhail Churnosov

Genome-wide Association Study