TY - JOUR
T1 - Item-level analyses reveal genetic heterogeneity in neuroticism
AU - Nagel, Mats
AU - Watanabe, Kyoko
AU - Stringer, Sven
AU - Posthuma, Danielle
AU - Van Der Sluis, Sophie
PY - 2018/3/2
Y1 - 2018/3/2
N2 - Genome-wide association studies (GWAS) of psychological traits are generally conducted on (dichotomized) sums of items or symptoms (e.g., case-control status), and not on the individual items or symptoms themselves. We conduct large-scale GWAS on 12 neuroticism items and observe notable and replicable variation in genetic signal between items. Within samples, genetic correlations among the items range between 0.38 and 0.91 (mean r g =.63), indicating genetic heterogeneity in the full item set. Meta-analyzing the two samples, we identify 255 genome-wide significant independent genomic regions, of which 138 are item-specific. Genetic analyses and genetic correlations with 33 external traits support genetic differences between the items. Hierarchical clustering analysis identifies two genetically homogeneous item clusters denoted depressed affect and worry. We conclude that the items used to measure neuroticism are genetically heterogeneous, and that biological understanding can be gained by studying them in genetically more homogeneous clusters.
AB - Genome-wide association studies (GWAS) of psychological traits are generally conducted on (dichotomized) sums of items or symptoms (e.g., case-control status), and not on the individual items or symptoms themselves. We conduct large-scale GWAS on 12 neuroticism items and observe notable and replicable variation in genetic signal between items. Within samples, genetic correlations among the items range between 0.38 and 0.91 (mean r g =.63), indicating genetic heterogeneity in the full item set. Meta-analyzing the two samples, we identify 255 genome-wide significant independent genomic regions, of which 138 are item-specific. Genetic analyses and genetic correlations with 33 external traits support genetic differences between the items. Hierarchical clustering analysis identifies two genetically homogeneous item clusters denoted depressed affect and worry. We conclude that the items used to measure neuroticism are genetically heterogeneous, and that biological understanding can be gained by studying them in genetically more homogeneous clusters.
UR - http://www.scopus.com/inward/record.url?scp=85042877381&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042877381&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042877381&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29500382
U2 - https://doi.org/10.1038/s41467-018-03242-8
DO - https://doi.org/10.1038/s41467-018-03242-8
M3 - Article
C2 - 29500382
SN - 2041-1723
VL - 9
SP - 1
EP - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 905
ER -