American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2012
Genome-wide association uncovers shared genetic effects among personality traits and mood states.
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Luciano Michelle, Huffman Jennifer E, Arias-Vásquez Alejandro, Vinkhuyzen Anna A E, Middeldorp Christel M, Giegling Ina, Payton Antony, Davies Gail, Zgaga Lina, Janzing Joost, Ke Xiayi, Galesloot Tessel, Hartmann Annette M, Ollier William, Tenesa Albert, Hayward Caroline, Verhagen Maaike, Montgomery Grant W, Hottenga Jouke-Jan, Konte Bettina, Starr John M, Vitart Veronique, Vos Pieter E, Madden Pamela A F, Willemsen Gonneke, Konnerth Heike, Horan Michael A, Porteous David J, Campbell Harry, Vermeulen Sita H, Heath Andrew C, Wright Alan, Polasek Ozren, Kovacevic Sanja B, Hastie Nicholas D, Franke Barbara, Boomsma Dorret I, Martin Nicholas G, Rujescu Dan, Wilson James F, Buitelaar Jan, Pendleton Neil, Rudan Igor, Deary Ian J
Аннотация
Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 × 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 × 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits.