Genome-wide analyses of self-reported empathy: correlations with autism, schizophrenia, and anorexia nervosa

AbstractAnorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using unbiased genome-wide methods, recent studies have associated a variety of genes with the disorder. We characterized these genes by projecting them into aggregated gene expression data from reference transcriptomic atlases of the prenatal and adult human brain. We found that genes from an induced stem cell study of anorexia nervosa are expressed at higher levels in the lateral parabrachial and the ventral tegmental areas. The adult expression enrichment of the lateral parabrachial is confirmed with genes from two independent genetic studies. In the fetal brain, enrichment of the ventral tegmental area is also observed for the six genes near the only common variant associated with the disorder (rs4622308). We also observed signals in the adult and fetal pontine raphe, but they were not observed when using the genes from the genetic studies. In addition to signals related to calcitonin gene-related peptide neurons and the tachykinin, we found more than the expected number of microglia marker genes within the gene sets. Using mouse transcriptomic data, we identified several anorexia nervosa associated genes that are differentially expressed during food deprivation. While these genes that respond to fasting are not enriched in the gene sets, we highlightRPS26which is proximal to rs4622308. We did not observe expression enrichment in the cingulate cortex or hypothalamus suggesting other targets for deep brain stimulation should be considered for severe cases. This work improves our understanding of the neurobiological causes of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Nature Genetics ◽

10.1038/s41588-019-0439-2 ◽

2019 ◽

Vol 51 (8) ◽

pp. 1207-1214 ◽

Cited By ~ 141

Author(s):

Hunna J. Watson ◽

◽

Zeynep Yilmaz ◽

Laura M. Thornton ◽

Christopher Hübel ◽

...

Keyword(s):

Anorexia Nervosa ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide

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DNA methylation in individuals with anorexia nervosa and in matched normal-eater controls: A genome-wide study

International Journal of Eating Disorders ◽

10.1002/eat.22374 ◽

2015 ◽

Vol 48 (7) ◽

pp. 874-882 ◽

Cited By ~ 36

Author(s):

Linda Booij ◽

Kevin F. Casey ◽

Juliana M. Antunes ◽

Moshe Szyf ◽

Ridha Joober ◽

...

Keyword(s):

Dna Methylation ◽

Anorexia Nervosa ◽

Genome Wide ◽

A Genome ◽

Genome Wide Study

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One size does not fit all. Genomics differentiates among binge-eating disorder, bulimia nervosa, and anorexia nervosa

10.1101/2020.03.24.20042648 ◽

2020 ◽

Author(s):

Christopher Hübel ◽

Mohamed Abdulkadir ◽

Moritz Herle ◽

Ruth J.F. Loos ◽

Gerome Breen ◽

...

Keyword(s):

Eating Disorders ◽

Anorexia Nervosa ◽

Eating Disorder ◽

Bulimia Nervosa ◽

Binge Eating ◽

Binge Eating Disorder ◽

Association Studies ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Polygenic Scores

AbstractObjectiveGenome-wide association studies have identified multiple genomic regions associated with anorexia nervosa. Relatively few or no genome-wide studies of other eating disorders, such as bulimia nervosa and binge-eating disorder, have been performed, despite their substantial heritability. Exploratively, we aimed to identify traits that are genetically associated with binge-type eating disorders.MethodWe calculated genome-wide polygenic scores for 269 trait and disease outcomes using PRSice v2.2 and their association with anorexia nervosa, bulimia nervosa, and binge-eating disorder in up to 640 cases and 17,050 controls from the UK Biobank. Significant associations were tested for replication in the Avon Longitudinal Study of Parents and Children (up to 217 cases and 3018 controls).ResultsIndividuals with binge-type eating disorders had higher polygenic scores than controls for other psychiatric disorders, including depression, schizophrenia, and attention deficit hyperactivity disorder, and higher polygenic scores for body mass index.DiscussionOur findings replicate some of the known comorbidities of eating disorders on a genomic level and motivate a deeper investigation of shared and unique genomic factors across the three primary eating disorders.

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An Atlas of Genetic Correlations across Human Diseases and Traits

10.1101/014498 ◽

2015 ◽

Cited By ~ 25

Author(s):

Brendan Bulik-Sullivan ◽

Hilary K Finucane ◽

Verneri Anttila ◽

Alexander Gusev ◽

Felix R Day ◽

...

Keyword(s):

Anorexia Nervosa ◽

Educational Attainment ◽

Genetic Correlation ◽

Complex Traits ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Significant Snps ◽

Modeling Framework ◽

Genome Wide ◽

Meta Analyses

Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use our method to estimate 300 genetic correlations among 25 traits, totaling more than 1.5 million unique phenotype measurements. Our results include genetic correlations between anorexia nervosa and schizophrenia/ body mass index and associations between educational attainment and several diseases. These results highlight the power of a polygenic modeling framework, since there currently are no genome-wide significant SNPs for anorexia nervosa and only three for educational attainment.

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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.17.15.18 ◽

2020 ◽

Author(s):

Watson HJ ◽

Yilmaz Z ◽

Thornton LM ◽

Hübel C ◽

Coleman JR ◽

...

Keyword(s):

Anorexia Nervosa ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide

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ANGI — Anorexia Nervosa Genetics Initiative

Twin Research and Human Genetics ◽

10.1017/thg.2020.24 ◽

2020 ◽

Vol 23 (2) ◽

pp. 135-136

Author(s):

Cynthia Bulik ◽

Martin Kennedy ◽

Tracey Wade

Keyword(s):

Anorexia Nervosa ◽

Genetic Variants ◽

Large Scale ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Genome Wide Association ◽

Life Threatening Illness ◽

Genome Wide ◽

Life Threatening

AbstractIdentification of genetic variants associated with eating disorders is underway. The Anorexia Nervosa Genetics Initiative, an initiative of the Klarman Family Foundation, has contributed to advancing the field, yielding a large-scale genome-wide association study published in Nature Genetics. Eight genetic variants significantly associated with anorexia nervosa were identified, along with patterns of genetic correlations that suggest both psychiatric and metabolic origins of this serious and life-threatening illness. This article details the role of Professor Nick Martin in contributing to this important collaboration.

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Erratum: A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

Scientific Reports ◽

10.1038/s41598-017-06409-3 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 2

Author(s):

Dong Li ◽

◽

Xiao Chang ◽

John J. Connolly ◽

Lifeng Tian ◽

...

Keyword(s):

Anorexia Nervosa ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Leptin Signaling ◽

Genome Wide ◽

A Genome ◽

Risk Locus

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Epigenetic modifications in anorexia nervosa patients and remitters compared to healthy control women

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.856 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S30-S31 ◽

Cited By ~ 1

Author(s):

N. Ramoz ◽

J. Clarke ◽

P. Gorwood

Keyword(s):

Anorexia Nervosa ◽

Candidate Genes ◽

Major Gene ◽

Small Samples ◽

Genome Wide ◽

Limited Effectiveness ◽

Healthy Control ◽

High Heritability ◽

Competing Interest ◽

Epigenetic Signatures

IntroductionAnorexia nervosa (AN) is the most severe in terms of morbidity psychiatric illness with the highest mortality rate increased by 23 fold. Treatments are limited effectiveness. AN has a strong genetic component with heritability at 70% but despite ∼ 200 studies no major gene was identified. Epigenetics, such as DNA methylation, is another component of heritability that could explain the high heritability. Methylation is poorly studied in AN from small samples, and is focused on few candidate genes among publications. Under publication, a first genome-wide methylation study investigated 10 restrictive type AN patients, 19 binging/purging type of AN patients and 15 normal eaters using DNAs from whole blood (Booij, 2015). Of the 480K CpG sites that can be methylated of Infinium Human Methylation450 BeadChip Kit, authors focused on 24,000 sites located close to genes and they identified candidate genes with a different profile of methylation between AN and controls.ObjectivesOur work is to replicate the results of Booji and also to investigate the AN remitters.AimsOur goal is to identify epigenetic signatures of the AN disorder and the prognostic of remission.MethodsTwenty-four AN patients, 24 AN remitters will be compared to 48 healthy control women for methylation using the Infinium Human Methylation450.ResultsAs Booji et al., we will compare methylation for 24,000 sites located close to genes for 24 AN, 24 remitters and 48 controls.ConclusionsWe expected to replicate the published results of Booji and to identify genes with a methylation signature specific of the AN remission.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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