Genetic Associations with Subjective Well-Being Also Implicate Depression and Neuroticism

We conducted a genome-wide association study of subjective well-being (SWB) in 298,420 individuals. We also performed auxiliary analyses of depressive symptoms ("DS";N= 161,460) and neuroticism (N= 170,910), both of which have a substantial genetic correlation with SWB (ρ≈-0.8). We identify three SNPs associated with SWB at genome-wide significance. Two of them are significantly associated with DS in an independent sample. In our auxiliary analyses, we identify 13 additional genome-wide-significant associations: two with DS and eleven with neuroticism, including two inversion polymorphisms. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are enriched. The discovery of genetic loci associated with the three phenotypes we study has proven elusive; our findings illustrate the payoffs from studying them jointly.

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A genome-wide association study identifies susceptibility loci for primary central nervous system lymphoma at 6p25.3 and 3p22.1: a LOC Network study

Neuro-Oncology ◽

10.1093/neuonc/noz088 ◽

2019 ◽

Vol 21 (8) ◽

pp. 1039-1048 ◽

Cited By ~ 4

Author(s):

Karim Labreche ◽

Mailys Daniau ◽

Amit Sud ◽

Philip J Law ◽

Louis Royer-Perron ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

B Cell ◽

Association Study ◽

Genome Wide Association Study ◽

Central Nervous System Lymphoma ◽

Genome Wide Association ◽

Non Hodgkin Lymphoma ◽

Genome Wide ◽

A Genome

AbstractBackgroundPrimary central nervous system lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin lymphoma. PCNSL is a distinct subtype of non-Hodgkin lymphoma, with over 95% of tumors belonging to the diffuse large B-cell lymphoma (DLBCL) group. We have conducted a genome-wide association study (GWAS) on immunocompetent patients to address the possibility that common genetic variants influence the risk of developing PCNSL.MethodsWe performed a meta-analysis of 2 new GWASs of PCNSL totaling 475 cases and 1134 controls of European ancestry. To increase genomic resolution, we imputed >10 million single nucleotide polymorphisms using the 1000 Genomes Project combined with UK10K as reference. In addition we performed a transcription factor binding disruption analysis and investigated the patterns of local chromatin by Capture Hi-C data.ResultsWe identified independent risk loci at 3p22.1 (rs41289586, ANO10, P = 2.17 × 10−8) and 6p25.3 near EXOC2 (rs116446171, P = 1.95 x 10−13). In contrast, the lack of an association between rs41289586 and DLBCL suggests distinct germline predisposition to PCNSL and DLBCL. We found looping chromatin interactions between noncoding regions at 6p25.3 (rs11646171) with the IRF4 promoter and at 8q24.21 (rs13254990) with the MYC promoter, both genes with strong relevance to B-cell tumorigenesis.ConclusionTo our knowledge this is the first study providing insight into the genetic predisposition to PCNSL. Our findings represent an important step in defining the contribution of common genetic variation to the risk of developing PCNSL.

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Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.1000 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 1000-1000 ◽

Cited By ~ 24

Author(s):

B. P. Schneider ◽

L. Li ◽

K. Miller ◽

D. Flockhart ◽

M. Radovich ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genetic Associations ◽

Genome Wide ◽

A Genome

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Genetics of fasting and postprandial metabolite levels are overlapping

Physiological Genomics ◽

10.1152/physiolgenomics.00101.2017 ◽

2018 ◽

Vol 50 (4) ◽

pp. 235-236

Author(s):

Ruifang Li-Gao ◽

Renée de Mutsert ◽

Frits R. Rosendaal ◽

Ko Willems van Dijk ◽

Dennis O. Mook-Kanamori

Keyword(s):

Association Study ◽

Human Body ◽

Genetic Basis ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genetic Associations ◽

Mixed Meal ◽

Genome Wide ◽

A Genome ◽

Metabolite Concentrations

In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a nonfasting state for the greater part of the day, and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were identified with significant changes after the meal, for which 38 gene-metabolite associations were analyzed. Of these 38 associations, 31 gene-metabolite associations were replicated with postprandial metabolite concentrations. These data indicate that the genetics of fasting and postprandial metabolite levels are significantly overlapping.

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Genome-wide Association Study of Pulmonary Function in Europeans and Africans from the UK Biobank Identifies Distinct Variants

10.1101/2022.01.07.22268836 ◽

2022 ◽

Author(s):

Musalula Sinkala ◽

Samar S. M. Elsheikh ◽

Mamana Mbiyavanga ◽

Joshua Cullinan ◽

Nicola Mulder

Keyword(s):

Pulmonary Function ◽

Genome Wide Association Study ◽

Well Being ◽

Genome Wide Association ◽

Significant Finding ◽

Uk Biobank ◽

Chromosome 11 ◽

Genome Wide ◽

A Genome ◽

The Uk

Pulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. FEV1, FVC, and PEF are quantitively used to assess pulmonary function. We conducted a genome-wide association analysis of pulmonary function in 383,471 individuals of European and 5,978 African descent represented in the UK Biobank. Here, we report 817 variants in Europeans and 3 in Africans associated (p-values < 5 x 10-8) with three pulmonary function parameters; FEV1, FVC and PEF. In addition to 377 variants in Europeans previously reported to be associated with phenotypes related to pulmonary function, we identified 330 novel loci, including an ISX intergenic variant rs369476290 on chromosome 22 in Africans and a KDM2A intron variant rs12790261 on chromosome 11 in Europeans. Remarkably, we find no shared variants among Africans and Europeans. Enrichment analyses of variants separately for each ancestry background revealed significant enrichment for terms related to pulmonary phenotypes in Europeans but not Africans. Further analysis of studies of pulmonary phenotypes revealed individuals of European background are disproportionally overrepresented in datasets compared to Africans, with the gap widening over the past five years. Our findings offer a better understanding of the different variants that modify pulmonary function in Africans and Europeans, a significant finding for future GWAS studies and medicine.

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A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases

Cell Discovery ◽

10.1038/s41421-020-00239-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xiaomin Liu ◽

Shanmei Tang ◽

Huanzi Zhong ◽

Xin Tong ◽

Zhuye Jie ◽

...

Keyword(s):

Gut Microbiome ◽

Genome Wide Association Study ◽

Association Studies ◽

Copy Number Variations ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genetic Associations ◽

Association Analyses ◽

Genome Wide ◽

A Genome

AbstractThe gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no <20% genetic contribution to the gut microbiota. Using common variants-, rare variants-, and copy number variations-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological, and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top two loci explaining 11% of the Prevotella–Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Our two-stage metagenome genome-wide association studies on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.

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A genome-wide association study finds novel genetic associations with broadly-defined headache in UK Biobank (N = 223,773)

10.1101/217786 ◽

2017 ◽

Author(s):

Weihua Meng ◽

Mark J Adams ◽

Harry L Hebert ◽

Ian J Deary ◽

Andrew M McIntosh ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Genome Wide Association ◽

Uk Biobank ◽

Genetic Associations ◽

Psychological Traits ◽

Genome Wide ◽

A Genome ◽

The Uk

AbstractHeadache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort. We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls. We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 × 10−8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 × 10−47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 × 10−15 in the LINC02210-CRHR1 gene was the top SNP.Positive relationships (P < 0.001) between multiple brain tissues and genetic associations were identified through tissue expression analysis, whereas no vascular related tissues showed significant relationships. We identified several significant positive genetic correlations between headache and other psychological traits including neuroticism, depressive symptoms, insomnia, and major depressive disorder.Our results suggest that brain function is closely related to broadly-defined headache. In addition, we also found that many psychological traits have genetic correlations with headache.

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Genome-Wide Association Study Reveals Genomic Region Associated with Mite-Recruitment Phenotypes in the Domesticated Grapevine (Vitis vinifera)

Genes ◽

10.3390/genes12071013 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1013

Author(s):

Erika R. LaPlante ◽

Margaret B. Fleming ◽

Zoë Migicovsky ◽

Marjorie Gail Weber

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Plant Traits ◽

Leaf Shape ◽

Common Garden ◽

Genome Wide Association ◽

Genetic Associations ◽

Predacious Mites ◽

Genome Wide ◽

A Genome

Indirect defenses are plant phenotypes that reduce damage by attracting natural enemies of plant pests and pathogens to leaves. Despite their economic and ecological importance, few studies have investigated the genetic underpinnings of indirect defense phenotypes. Here, we present a genome-wide association study of five phenotypes previously determined to increase populations of beneficial (fungivorous and predacious) mites on grape leaves (genus Vitis): leaf bristles, leaf hairs, and the size, density, and depth of leaf domatia. Using a common garden genetic panel of 399 V. vinifera cultivars, we tested for genetic associations of these phenotypes using previously obtained genotyping data from the Vitis9kSNP array. We found one single nucleotide polymorphism (SNP) significantly associated with domatia density. This SNP (Chr5:1160194) is near two genes of interest: Importin Alpha Isoform 1 (VIT_205s0077g01440), involved in downy mildew resistance, and GATA Transcription Factor 8 (VIT_205s0077g01450), involved in leaf shape development. Our findings are among the first to examine the genomic regions associated with ecologically important plant traits that facilitate interactions with beneficial mites, and suggest promising candidate genes for breeding and genetic editing to increase naturally occurring predator-based defenses in grapevines.

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A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)

EBioMedicine ◽

10.1016/j.ebiom.2018.01.023 ◽

2018 ◽

Vol 28 ◽

pp. 180-186 ◽

Cited By ~ 21

Author(s):

Weihua Meng ◽

Mark J. Adams ◽

Harry L. Hebert ◽

Ian J. Deary ◽

Andrew M. McIntosh ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Uk Biobank ◽

Genetic Associations ◽

Genome Wide ◽

A Genome

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Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank

10.1101/130229 ◽

2017 ◽

Cited By ~ 2

Author(s):

Lynsey S. Hall ◽

Mark J. Adams ◽

Aleix Arnau-Soler ◽

Toni-Kim Clarke ◽

David M. Howard ◽

...

Keyword(s):

Multiple Testing ◽

Well Being ◽

Subjective Well Being ◽

Uk Biobank ◽

Genetic Associations ◽

Sample Sizes ◽

Genome Wide ◽

Generation Scotland ◽

A Genome ◽

Significant Locus

AbstractFew replicable genetic associations for Major Depressive Disorder (MDD) have been identified. However recent studies of depression have identified common risk variants by using either a broader phenotype definition in very large samples, or by reducing the phenotypic and ancestral heterogeneity of MDD cases. Here, a range of genetic analyses were applied to data from two large British cohorts, Generation Scotland and UK Biobank, to ascertain whether it is more informative to maximize the sample size by using data from all available cases and controls, or to use a refined subset of the data - stratifying by MDD recurrence or sex. Meta-analysis of GWAS data in males from these two studies yielded one genome-wide significant locus on 3p22.3. Three associated genes within this region (CRTAP, GLB1, and TMPPE) were significantly associated in subsequent gene-based tests. Meta-analyzed MDD, recurrent MDD and female MDD were each genetically correlated with 6 of 200 health-correlated traits, namely neuroticism, depressive symptoms, subjective well-being, MDD, a cross-disorder phenotype and Bipolar Disorder. Meta-analyzed male MDD showed no statistically significant correlations with these traits after correction for multiple testing. Whilst stratified GWAS analysis revealed a genome-wide significant locus for male MDD, the lack of independent replication, the equivalent SNP-based heritability estimates and the consistent pattern of genetic correlation with other health-related traits suggests that phenotypic stratification in currently available sample sizes is currently weakly justified. Based upon existing studies and our findings, the strategy of maximizing sample sizes is likely to provide the greater gain.

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