Duo Shared Genomic Segment analysis identifies a genome-wide significant risk locus at 18q21.33 in myeloma pedigrees

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we performed a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identified a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 x 10-8; KMT5B). We also identified a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N=1287) at 6p21.32 (rs3916765; P = 1.51 x 10 -10; HLA). Our results inform on AML etiology by identifying putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

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Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Nature Communications ◽

10.1038/s41467-021-26551-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wei-Yu Lin ◽

Sarah E. Fordham ◽

Eric Hungate ◽

Nicola J. Sunter ◽

Claire Elstob ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Association Studies ◽

Significant Risk ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome ◽

Risk Locus ◽

Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

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Abstract P629: Genome-Wide Association Study of Individuals of Native Hawaiian Ancestry Reveals Unique Genetic Risk Factors for Stroke and Myocardial Infarction

Stroke ◽

10.1161/str.52.suppl_1.p629 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Stacy C Brown ◽

Cameron Both ◽

Julian N Acosta ◽

Natalia Szejko ◽

Victor Torres ◽

...

Keyword(s):

Myocardial Infarction ◽

Ischemic Stroke ◽

Association Study ◽

Genome Wide Association Study ◽

Native Hawaiian ◽

European Ancestry ◽

Intronic Region ◽

Genome Wide ◽

A Genome ◽

Risk Locus

Background: Several genetic susceptibility risk loci for ischemic stroke have been identified. However, the relative dearth of genetic data from populations of non-European ancestry has the potential to create disparities in access to genomics-based precision medicine strategies. Individuals of Native Hawaiian ancestry represent a particularly understudied group in stroke genomics research despite facing high rates of cerebrovascular disease. Hypothesis: Genetic variants associated with stroke differ between Native Hawaiians and previously studied groups of predominantly European ancestry. Methods: We conducted a genome-wide (GW) association study of stroke and myocardial infarction (MI) in an adult population of Native Hawaiian ancestry, using data from the Multiethnic Cohort study (MEC). Genetic information was ascertained via genome-wide array genotyping using the AB OpenArray and TaqMan platforms followed by imputation to 1000 Genomes reference panels. We pursued replication of variants that were GW significant (p<5x10 -8 ) or yielded suggestive associations (p<5x10 -7 ) in the prior stroke GW association study MEGASTROKE. Results: We identified 2,104 individuals (1,089 [51.8%] female) of Native Hawaiian ancestry, including 173 cases and 1,931 controls. We identified one novel susceptibility risk locus at a narrow intronic region located at chromosome q26.2 (top associated SNP 3:169096251, OR 2.48, 95%CI 1.81-3.41; p=1.93x10 -8 ), overlying the MECOM gene. We also identified 9 other suggestive risk loci at p<5x10 -7 . When replicating in MEGASTROKE, q26.2 did not have available counterpart variants to analyze, and 3 out of 9 suggestive signals were associated with ischemic stroke subtypes at p<0.05. Conclusions: We report the first GW association study of ischemic stroke and myocardial infarction in a Native Hawaiian population. We identified one susceptibility risk locus at q26.2, located in a narrow intronic region of MECOM, a gene that codes for a histone-lysine N-methyltransferase that has transcriptional regulation and oncoprotein functions. The lack of available replication data for this locus in the large MEGASTROKE collaboration emphasizes the importance of developing genomic resources across ancestral groups.

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A significant risk locus on 19q13 for bipolar disorder identified using a combined genome-wide linkage and copy number variation analysis

BioData Mining ◽

10.1186/s13040-015-0076-y ◽

2015 ◽

Vol 8 (1) ◽

Author(s):

Magnus Lekman ◽

Robert Karlsson ◽

Lisette Graae ◽

Ola Hössjer ◽

Ingrid Kockum

Keyword(s):

Bipolar Disorder ◽

Copy Number Variation ◽

Copy Number ◽

Significant Risk ◽

Variation Analysis ◽

Copy Number Variation Analysis ◽

Genome Wide ◽

Number Variation ◽

Risk Locus

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Tu1943a A Genome-Wide Association Study Identifies DSE-FAM26F As a Risk Locus for Ulcerative Colitis

Gastroenterology ◽

10.1016/s0016-5085(14)63198-x ◽

2014 ◽

Vol 146 (5) ◽

pp. S-878

Author(s):

Javier P. Gisbert ◽

Antonio Julià ◽

Maria Chaparro ◽

Valle García-Sánchez ◽

Fernando Gomollon ◽

...

Keyword(s):

Ulcerative Colitis ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Risk Locus

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Genome-wide association study implicates CHRNA2 in cannabis use disorder

10.1101/237321 ◽

2017 ◽

Cited By ~ 5

Author(s):

Ditte Demontis ◽

Veera Manikandan Rajagopal ◽

Thomas D. Als ◽

Jakob Grove ◽

Jonatan Pallesen ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Significant Risk ◽

The United States ◽

Cannabis Use ◽

Genome Wide Association ◽

Cannabis Use Disorder ◽

Genome Wide ◽

Independent Population ◽

A Genome

Introductory paragraphCannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.

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Identification of a Risk Locus at 7p22.3 for Schizophrenia and Bipolar Disorder in East Asian Populations

Frontiers in Genetics ◽

10.3389/fgene.2021.789512 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenqiang Li ◽

Chu-Yi Zhang ◽

Jiewei Liu ◽

Fanglin Guan ◽

Minglong Shao ◽

...

Keyword(s):

Bipolar Disorder ◽

Whole Blood ◽

Genome Wide Association Study ◽

East Asian ◽

Mrna Level ◽

Risk Genes ◽

Genome Wide ◽

A Genome ◽

Risk Snps ◽

Risk Locus

Background: Shared psychopathological features and mechanisms have been observed between schizophrenia (SZ) and bipolar disorder (BD), but their common risk genes and full genetic architectures remain to be fully characterized. The genome-wide association study (GWAS) datasets offer the opportunity to explore this scientific question using combined genetic data from enormous samples, ultimately allowing a better understanding of the onset and development of these illnesses.Methods: We have herein performed a genome-wide meta-analysis in two GWAS datasets of SZ and BD respectively (24,600 cases and 40,012 controls in total, discovery sample), followed by replication analyses in an independent sample of 4,918 SZ cases and 5,506 controls of Han Chinese origin (replication sample). The risk SNPs were then explored for their correlations with mRNA expression of nearby genes in multiple expression quantitative trait loci (eQTL) datasets.Results: The single nucleotide polymorphisms (SNPs) rs1637749 and rs3800908 at 7p22.3 region were significant in both discovery and replication samples, and exhibited genome-wide significant associations when combining all East Asian SZ and BD samples (29,518 cases and 45,518 controls). The risk SNPs were also significant in GWAS of SZ and BD among Europeans. Both risk SNPs significantly predicted lower expression of MRM2 in the whole blood and brain samples in multiple datasets, which was consistent with its reduced mRNA level in the brains of SZ patients compared with normal controls. The risk SNPs were also associated with MAD1L1 expression in the whole blood sample.Discussion: We have identified a novel genome-wide risk locus associated with SZ and BD in East Asians, adding further support for the putative common genetic risk of the two illnesses. Our study also highlights the necessity and importance of mining public datasets to explore risk genes for complex psychiatric diseases.

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