An Atlas of Genetic Correlations across Human Diseases and Traits

Bulik-Sullivan, Brendan; Finucane, Hilary; Anttila, Verneri; Gusev, Alexander; Day, Felix R.; Duncan, Laramie; Perry, John R. B.; Patterson, Nick; Robinson, Elise; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

doi:10.1101/014498

Cited by 1,104 publications

(2,076 citation statements)

References 75 publications

Supporting

Mentioning

1,963

Contrasting

Unclassified

Order By: Relevance

“…Based on previously identified genetic links between restless legs syndrome (RLS) and insomnia symptoms 9,10 , we tested a GRS of 20 SNPs for RLS 34 and found association with frequent insomnia symptoms (OR=1.03 (1.02-1.04) per RLS risk allele, p=5.69x10 -53 ; Supplementary Table 18). To test the proportion of variance frequent insomnia symptoms shares with other traits based on genetic overlap, we performed genome-wide genetic correlation analyses between our frequent insomnia symptoms GWAS and 233 traits with public GWAS summary statistics 25,26,35,36 . We found and strong positive genetic correlations (p≤2x10 -3 ) between frequent insomnia symptoms and adiposity traits, coronary artery disease, neuroticism, smoking behavior and depressive symptoms and disorder.…”

mentioning

confidence: 99%

Biological and clinical insights from genetics of insomnia symptoms

Lane

Jones

Dashti

et al. 2018

Preprint

View full text Add to dashboard Cite

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.

show abstract

mentioning

confidence: 99%

Biological and clinical insights from genetics of insomnia symptoms

Lane

Jones

Dashti

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…20 We here show that customized population-specific arrays for imputation-based GWA testing can be a valuable tool to generate high quality GWA results. a Since the imputation of minor alleles is dependent on the platform data, we choose the minor allele frequency of the 1000G population to be the value determining the MAF category.…”

Section: Discussionmentioning

confidence: 84%

A method to customize population-specific arrays for genome-wide association testing

et al. 2016

View full text Add to dashboard Cite

As an example of optimizing population-specific genotyping assays using a whole-genome sequence reference set, we detail the approach that followed to design the Axiom-NL array which is characterized by an improved imputation backbone based on the Genome of the Netherlands (GoNL) reference sequence and, compared with earlier arrays, a more comprehensive inclusion of SNPs on chromosomes X, Y, and the mitochondria. Common variants on the array were selected to be compatible with the Illumina Psych Array and the Affymetrix UK Biobank Axiom array. About 3.5% of the array (23 977 markers) represents SNPs from the GWAS catalog, including SNPs at FTO, APOE, Ion-channels, killer-cell immunoglobulin-like receptors, and HLA. Around 26 000 markers associated with common psychiatric disorders are included, as well as 6705 markers suggested to be associated with fertility and twinning. The platform can thus be used for risk profiling, detection of new variants, as well as ancestry determination. Results of coverage tests in 249 unrelated subjects with GoNL-based sequence data show that after imputation with 1000G as a reference, the median concordance between original and imputed genotypes is above 98%. The median imputation quality R 2 for MAF thresholds of 0.001, 0.01, 0.05, and 40.05 are 0.05, 0.28, 0.80, 0.99, respectively, for the 1000G imputed SNPs, with a similar quality for the autosomes and X chromosome, showing a good genome-wide coverage for association studies after imputation. 3,4 to hormones, 5 personality, 6 educational attainment, 7 and lifestyle characteristics. [8][9][10] The major technology behind these successes is the relatively cheap genotyping, in comparison with full genome sequencing, of DNA samples on genotyping arrays with 300 K-5 M single-nucleotide polymorphisms (SNPs), followed by imputation of the unmeasured SNPs. Initially, the contents of these arrays were determined by the manufacturers, but recently companies also allow researchers to select the variants on an array. Here, we focus on the Axiom array, a genotyping solution from Affymetrix, Inc., which provides a high throughput platform for high-density SNP genotyping on a diverse range of sample types. This array has been used for several large population-wide genome-screening projects including the UK biobank 11 and the GERA cohorts. 12 We describe a similar custommade Axiom array for the Netherlands population, the Axiom-NL that allows good imputation and enhances association, and risk score analysis on DNA samples collected within Dutch Biobanks, such as the large number of Biobanks collaborating in BBMRI-NL. 13 Notwithstanding the application to this specific population, the SNP selection procedures and coverage testing can provide a general guideline for customizing the Axiom array in other populations for which valid reference sequence genomes are available. MATERIALS AND METHODS SNP selection for the Axiom-NL arrayAn overview of the SNP selection is provided in Figure 1, a stepwise procedure of the selection is given in the Supple...

show abstract

“…Last, GREML and LDSC can be used to explore the genetic correlation of traits 14,15 . This may be due to pleiotropy of variants, to close proximity and linkage of multiple variants that have an impact on different traits, or to long-range gametic phase dis equilibrium caused by cross-trait assortative mating.…”

mentioning

confidence: 99%

“…This may be due to pleiotropy of variants, to close proximity and linkage of multiple variants that have an impact on different traits, or to long-range gametic phase dis equilibrium caused by cross-trait assortative mating. Bivariate analyses have been used to clarify expected genetic correlations between traits, for instance, hypertension and type 2 diabetes mellitus 14 or high-density lipoprotein (HDL) and triglyceride levels 15 . However, these approaches have also highlighted genetic correlations that may have been previously unexpected, for instance, substantial positive genetic correlations among bipolar disorder, major depression and schizophrenia 10,15 .…”

mentioning

confidence: 99%

Using partitioned heritability methods to explore genetic architecture

Evans

2018

Nat Rev Genet

View full text Add to dashboard Cite

An Atlas of Genetic Correlations across Human Diseases and Traits

Cited by 1,104 publications

References 75 publications

Biological and clinical insights from genetics of insomnia symptoms

Biological and clinical insights from genetics of insomnia symptoms

A method to customize population-specific arrays for genome-wide association testing

Using partitioned heritability methods to explore genetic architecture

Contact Info

Product

Resources

About