title: Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.
abstract: Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: Fullerton
authors.forename: Matthew
authors.initials: M
authors.lastname: Cubin
authors.forename: Hemant
authors.initials: H
authors.lastname: Tiwari
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wang
authors.forename: Amarjit
authors.initials: A
authors.lastname: Bomhra
authors.forename: Stuart
authors.initials: S
authors.lastname: Davidson
authors.forename: Sue
authors.initials: S
authors.lastname: Miller
authors.forename: Christopher
authors.initials: C
authors.lastname: Fairburn
authors.forename: Guy
authors.initials: G
authors.lastname: Goodwin
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.forename: Simon
authors.initials: S
authors.lastname: Fiddy
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000328:Adult; D002874:Chromosome Mapping / Q000379:methods*; D004739:England; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009497:Neurotic Disorders / Q000235:genetics; D010552:Personality Assessment; D010554:Personality Disorders / Q000235:genetics*; D040641:Quantitative Trait Loci; D012044:Regression Analysis; D035781:Siblings; D011795:Surveys and Questionnaires
chemical_list: D005819:Genetic Markers