Asset Details
Do you wish to reserve the book?
Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways
Do you wish to request the book?
Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways
2018
Overview
Neuroticism is an important risk factor for psychiatric traits, including depression
1
, anxiety
2
,
3
, and schizophrenia
4
–
6
. At the time of analysis, previous genome-wide association studies
7
–
12
(GWAS) reported 16 genomic loci associated to neuroticism
10
–
12
. Here we conducted a large GWAS meta-analysis (
n
= 449,484) of neuroticism and identified 136 independent genome-wide significant loci (124 new at the time of analysis), which implicate 599 genes. Functional follow-up analyses showed enrichment in several brain regions and involvement of specific cell types, including dopaminergic neuroblasts (
P
= 3.49 × 10
−8
), medium spiny neurons (
P
= 4.23 × 10
−8
), and serotonergic neurons (
P
= 1.37 × 10
−7
). Gene set analyses implicated three specific pathways: neurogenesis (
P
= 4.43 × 10
−9
), behavioral response to cocaine processes (
P
= 1.84 × 10
−7
), and axon part (
P
= 5.26 × 10
−8
). We show that neuroticism’s genetic signal partly originates in two genetically distinguishable subclusters
13
(‘depressed affect’ and ‘worry’), suggesting distinct causal mechanisms for subtypes of individuals. Mendelian randomization analysis showed unidirectional and bidirectional effects between neuroticism and multiple psychiatric traits. These results enhance neurobiological understanding of neuroticism and provide specific leads for functional follow-up experiments.
A meta-analysis of genome-wide association studies for neuroticism identifies novel loci, pathways and potential drug targets. Further analysis implicates specific brain regions and evaluates genetic overlap with other neuropsychiatric traits.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Animal Genetics and Genomics
/ Anxiety Disorders - genetics
/ Biomedical and Life Sciences
/ Brain
/ Cocaine
/ Female
/ Genes
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study - methods
/ Genomes
/ Genomics
/ Humans
/ Letter
/ Male
/ Neurons
/ Neurosis
/ Polymorphism, Single Nucleotide
/ Power
