Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.
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.
Fullerton
Jan
J
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Cubin
Matthew
M
Tiwari
Hemant
H
Wang
Chenxi
C
Bomhra
Amarjit
A
Davidson
Stuart
S
Miller
Sue
S
Fairburn
Christopher
C
Goodwin
Guy
G
Neale
Michael C
MC
Fiddy
Simon
S
Mott
Richard
R
Allison
David B
DB
Flint
Jonathan
J
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
D005819:Genetic Markers