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 con...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Society of Human Genetics
2003
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| Subjects: |
| _version_ | 1797092821849604096 |
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| author | Fullerton, J Cubin, M Tiwari, H Wang, C Bomhra, A Davidson, S Miller, S Fairburn, C Goodwin, G Neale, M Fiddy, S Mott, R Allison, D Flint, J |
| author_facet | Fullerton, J Cubin, M Tiwari, H Wang, C Bomhra, A Davidson, S Miller, S Fairburn, C Goodwin, G Neale, M Fiddy, S Mott, R Allison, D Flint, J |
| author_sort | Fullerton, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:51:31Z |
| format | Journal article |
| id | oxford-uuid:c16e3469-900b-4641-b942-59291ecc4355 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:51:31Z |
| publishDate | 2003 |
| publisher | American Society of Human Genetics |
| record_format | dspace |
| spelling | oxford-uuid:c16e3469-900b-4641-b942-59291ecc43552022-03-27T06:01:26ZLinkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticismJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c16e3469-900b-4641-b942-59291ecc4355PsychiatryGenetics (medical sciences)EnglishOxford University Research Archive - ValetAmerican Society of Human Genetics2003Fullerton, JCubin, MTiwari, HWang, CBomhra, ADavidson, SMiller, SFairburn, CGoodwin, GNeale, MFiddy, SMott, RAllison, DFlint, JSeveral 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. |
| spellingShingle | Psychiatry Genetics (medical sciences) Fullerton, J Cubin, M Tiwari, H Wang, C Bomhra, A Davidson, S Miller, S Fairburn, C Goodwin, G Neale, M Fiddy, S Mott, R Allison, D Flint, J Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title | Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title_full | Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title_fullStr | Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title_full_unstemmed | Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title_short | Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism |
| title_sort | linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci that influence variation in the human personality trait neuroticism |
| topic | Psychiatry Genetics (medical sciences) |
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