Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Thomson, P. A., 2007 PMID: 16940976
Citation	Thomson, P. A., A. Christoforou, et al. (2007). "Association of Neuregulin 1 with schizophrenia and bipolar disorder in a second cohort from the Scottish population." Mol Psychiatry 12(1): 94-104.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	368 BP patients, 386 SCZ patients and 455 controls
SNP/Region/Marker Size	40 SNPs
Predominant Ethnicity	Caucasian
Population	Scottish
Gender	SCZ (276 male and 110 female), BP (160 male, 208 female), control (237 male, 218 female)

Detail Info

Sample Diagnosis	DSM-IV criteria by using The Schedule for Affective Disorders and Schizophrenia-lifetime version (SADS-L)
Sample Status	Subjects were inpatients or outpatients of hospitals in South East or South Central Scotland, including 368 BP patients and 386 SCZ patients.
Technique	genotyping using Bead Array technology and TaqMan assays
Statistical Method	Case-control association analyses were performed using the Unphased suite of programmes. Haplotypes were estimated in Unphased using an EM algorithm. Single-marker and sliding-window analyses of two- to four- SNP haplotypes were performed using the program Cocaphase. The nominal P-values given are two-tailed and uncorrected for multiple testing. An experiment-wide significance threshold was calculated using the method by Nyholt. P-values meeting this threshold were subsequently subjected to permutation analysis (1000 permutations) using Cocaphase.
Result Summary	Haplotypes in two regions met an experiment-wide significance threshold of P=0.0016 (Nyholt's SpD) and were permuted to correct for multiple testing. Region A overlaps with the Icelandic haplotype and shows nominal association with schizophrenia (P=0.00032), bipolar disorder (P=0.0011), and the combined case group (P=0.0017). This region includes the 5' exon of the NRG1 GGF2 isoform and overlaps the expressed sequence tag (EST) cluster Hs.97362. However, no haplotype in Region A remains significant after permutation analysis (P>0.05). Region B contains a haplotype associated with both schizophrenia (P=0.00014), and the combined case group (P=0.000062), although it does not meet Nyholt's threshold in bipolar disorder alone (P=0.0022). This haplotype remained significant after permutation analysis in both the schizophrenia and combined case groups (P=0.024 and P=0.016, respectively). It spans a approximately 136 kb region that includes the coding sequence of the sensory and motor neuron derived factor (SMDF) isoform and 3' exons of all other known NRG1 isoforms.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 36)

SNP	Related Gene(s)	Statistical Values	Author Comments	Result Category
rs1545961	NRG1	Individual P-value = 0.0895 for BP, Individual P-value = 0.1336 for SCZ and BP		Negative
rs1948098	NRG1	Individual P-value = 0.5504 for BP, Individual P-value = 0.3572 for SCZ and BP		Negative
rs2347501	NRG1 NRG1-IT3	Individual P-value = 0.6884 for BP, Individual P-value = 0.5315 for SCZ and BP		Negative
rs2439286	NRG1	Individual P-value = 0.5884 for BP, Individual P-value = 0.5518 for SCZ and BP		Negative
rs2439300	NRG1	Individual P-value = 0.4668 for BP, Individual P-value = 0.9469 for SCZ and BP		Negative
rs2439305	NRG1	Individual P-value = 0.917 for BP, Individual P-value = 0.752 for SCZ and BP		Negative
rs2919390	NRG1	Individual P-value = 0.0793 for BP, Individual P-value = 0.0105 for SCZ and BP	This marker is nominally significant in the combined sample This marker is nominally significant in the combined sample	Positive
rs327329	NRG1	Individual P-value = 0.8399 for BP, Individual P-value = 0.7353 for SCZ and BP		Negative
rs3757930	NRG1	Individual P-value = 0.16 for BP, Individual P-value = 0.1164 for SCZ and BP	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Negative
rs4298458	NRG1	Individual P-value = 0.454 for BP, Individual P-value = 0.9032 for SCZ and BP		Negative
rs4513929	NRG1	Individual P-value = 0.3258 for BP, Individual P-value = 0.9227 for SCZ and BP		Negative
rs4733132	NRG1	Individual P-value = 0.211 for BP, Individual P-value = 0.2859 for SCZ and BP		Negative
rs4733140	NRG1	Individual P-value = 0.3492 for BP, Individual P-value = 0.8239 for SCZ and BP	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Negative
rs553950	NRG1	Individual P-value = 0.0287 for BP, Individual P-value = 0.0109 for SCZ and BP	This SNP is nominally significant in all three groups: BP, S...... This SNP is nominally significant in all three groups: BP, SCZ and combined. More...	Positive
rs6468099	NRG1	Individual P-value = 0.5127 for BP, Individual P-value = 0.5716 for SCZ and BP		Negative
rs6986716	NRG1	Individual P-value = 0.3505 for BP, Individual P-value = 0.5832 for SCZ and BP		Negative
rs7007662	NRG1 NRG1-IT1	Individual P-value = 0.963 for BP, Individual P-value = 0.7981 for SCZ and BP		Negative
rs6988339	NRG1	Individual P-value = 0.0324 for BP, Individual P-value = 0.0058 for SCZ and BP	This marker is nominally significant in the combined sample This marker is nominally significant in the combined sample	Positive
rs726908	NRG1	Individual P-value = 0.5682 for BP, Individual P-value = 0.5578 for SCZ and BP		Negative
rs7015249	NRG1	Individual P-value = 0.7533 for BP, Individual P-value = 0.3427 for SCZ and BP		Negative
rs9656744	NRG1	Individual P-value = 0.451 for BP, Individual P-value = 0.5984 for SCZ and BP	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Negative
rs901561	NRG1	Individual P-value = 0.9317 for BP, Individual P-value = 0.9163 for SCZ and BP		Negative
rs9886497	NRG1	Individual P-value = 0.5277 for BP, Individual P-value = 0.2653 for SCZ and BP		Negative
rs10091429	NRG1	Individual P-value = 0.3881 for BP, Individual P-value = 0.9077 for SCZ and BP		Negative
rs10103750	NRG1	Individual P-value = 0.7349 for BP, Individual P-value = 0.6566 for SCZ and BP	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Negative
rs10096770	NRG1	Individual P-value = 0.37 for BP, Individual P-value = 0.5636 for SCZ and BP		Negative
rs10095694	NRG1	Individual P-value = 0.039 for BP, Individual P-value = 0.006 for SCZ and BP	This marker is nominally significant in the combined sample This marker is nominally significant in the combined sample	Positive
rs10093464	NRG1	Individual P-value = 0.7516 for BP, Individual P-value = 0.9223 for SCZ and BP		Negative
rs10954842	NRG1	Individual P-value = 0.6394 for BP, Individual P-value = 0.9317 for SCZ and BP		Negative
rs10954811	NRG1	Individual P-value = 0.9292 for BP, Individual P-value = 0.8101 for SCZ and BP		Negative
rs10503932	NRG1	Individual P-value = 0.5448 for BP, Individual P-value = 0.494 for SCZ and BP	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Negative
rs10113797	NRG1	Individual P-value = 0.3788 for BP, Individual P-value = 0.1981 for SCZ and BP		Negative
rs1503491	NRG1	Individual P-value = 0.2371 for BP, Individual P-value = 0.7019 for SCZ and BP		Negative
rs1487141	NRG1	Individual P-value = 0.7254 for BP, Individual P-value = 0.8195 for SCZ and BP		Negative
rs1481762	NRG1 NRG1-IT1	Individual P-value = 0.6521 for BP, Individual P-value = 0.5402 for SCZ and BP		Negative
rs1481747	NRG1	Individual P-value = 0.8464 for BP, Individual P-value = 0.9216 for SCZ and BP		Negative

Haplotypes reported by this study for BD (count: 29)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs10095694 - rs2919390 - rs6988339		NRG1	P-value = 0.0099 for BP, P-value = 0.0002 for SCZ and BP		Positive
rs10095694 - rs2919390		NRG1	P-value = 0.0184 for BP, P-value = 0.0016 for SCZ and BP		Positive
rs2439286 - rs10095694		NRG1	P-value = 0.0274 for BP, P-value = 0.0028 for SCZ and BP		Positive
rs1503491 - rs553950 - rs327329 - rs7007662		NRG1	P-value = 0.0029 for SZ and BP combined		Positive
rs1503491 - rs553950 - rs327329	T-T-T	NRG1	P-value = 0.0017 for SZ and BP combined		Positive
rs1503491 - rs553950		NRG1	P-value = 0.0117 for SZ and BP combined		Positive
rs10954811 - rs1503491 - rs553950 - rs327329		NRG1	P-value = 0.0018 for SZ and BP combined		Positive
rs10954811 - rs1503491 - rs553950		NRG1	P-value = 0.0078 for SZ and BP combined		Positive
rs10113797 - rs10954811 - rs1503491 - rs553950		NRG1	P-value = 0.0071 for SZ and BP combined		Positive
rs10095694 - rs2919390 - rs6988339 - rs3757930		NRG1	P-value = 0.0114 for BP, P-value = 0.0003 for SCZ and BP		Positive
rs2439286 - rs10095694 - rs2919390		NRG1	P-value = 0.0224 for BP, P-value = 0.0017 for SCZ and BP		Positive
rs2439286 - rs10095694 - rs2919390 - rs6988339		NRG1	P-value = 0.0074 for BP, P-value = 0.0002 for SCZ and BP		Positive
rs2439300 - rs2439286 - rs10095694 - rs2919390		NRG1	P-value = 0.0097 for SZ and BP combined		Positive
rs2439305 - rs2439300 - rs2439286 - rs10095694		NRG1	P-value = 0.0098 for SZ and BP combined		Positive
rs2919390 - rs6988339		NRG1	P-value = 0.0143 for BP, P-value = 0.0008 for SCZ and BP		Positive
rs2919390 - rs6988339 - rs3757930		NRG1	P-value = 0.0022 for BP, P-value = 0.0001 for SCZ and BP	the most significant haplotype in SCZ was also nominally sig...... the most significant haplotype in SCZ was also nominally significant in the BP sample; this was the only haplotype to withstand permutation analysis in this study, identifying a new region of association with both schizophrenia and the combined case group in the Scottish population More...	Positive
rs2919390 - rs6988339 - rs3757930 - rs10103750		NRG1	P-value = 0.0019 for BP, P-value = 0.0001 for SCZ and BP		Positive
rs327329 - rs7007662 - rs1481762		NRG1	P-value = 0.0299 for BP		Positive
rs327329 - rs7007662 - rs1481762 - rs726908		NRG1	P-value = 0.0072 for BP		Positive
rs3757930 - rs10103750		NRG1	P-value = 0.0216 for BP		Positive
rs3757930 - rs10103750 - rs10503932		NRG1	P-value = 0.0045 for BP		Positive
rs3757930 - rs10103750 - rs10503932 - rs9656744		NRG1	P-value = 0.0078 for BP		Positive
rs4298458 - SNP8NRG241930 - SNP8NRG243177 - rs10113797		NRG1	P-value = 0.0269 for BP		Positive
rs553950 - rs327329 - rs7007662		NRG1	P-value = 0.0011 for BP, P-value = 0.0034 for SZ and BP combined	the haplotype is nominally associated with BP alone and span...... the haplotype is nominally associated with BP alone and spans LD blocks 3 and 4 More...	Positive
rs553950 - rs327329 - rs7007662 - rs1481762		NRG1	P-value = 0.0064 for BP, P-value = 0.0146 for SZ and BP combined		Positive
rs6988339 - rs3757930		NRG1	P-value = 0.0045 for BP, P-value = 0.0004 for SCZ and BP		Positive
rs6988339 - rs3757930 - rs10103750 - rs10503932		NRG1	P-value = 0.0117 for BP, P-value = 0.002 for SCZ and BP		Positive
rs6988339 - rs3757930 - rs10103750		NRG1	P-value = 0.0044 for BP, P-value = 0.0005 for SCZ and BP		Positive
SNP8NRG221533 - rs4298458 - SNP8NRG241930 - SNP8NRG243177		NRG1	P-value = 0.0045 for BP	In the BP sample, a four-SNP haplotype was nominally signifi...... In the BP sample, a four-SNP haplotype was nominally significant at the individual level More...	Positive

Other variants reported by this study for BD (count: 4)

Variant Name	Related Gene	Type	Statistical Values	Result Category
NRG1 SNP8NRG221132	NRG1	point mutation	Individual P-value = 0.5946 for BP, Individual P-value = 0.7566 for SCZ and BP	Negative
NRG1 SNP8NRG221533	NRG1	point mutation	Individual P-value = 0.9317 for BP, Individual P-value = 0.7929 for SCZ and BP	Negative
NRG1 SNP8NRG241930	NRG1	point mutation	Individual P-value = 0.9192 for BP, Individual P-value = 0.8147 for SCZ and BP	Negative
NRG1 SNP8NRG243177	NRG1	point mutation	Individual P-value = 0.3379 for BP, Individual P-value = 0.5341 for SCZ and BP	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
NRG1	Our study identifies a new of NRG1 region involved in schizophrenia and bipolar disorder in the Scot...... Our study identifies a new of NRG1 region involved in schizophrenia and bipolar disorder in the Scottish population. More...	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
SZ	rs10093464	NRG1	Individual P-value = 0.6394 for SCZ , Individual P-value = 0.9223 for SCZ and BP		Negative
SZ	rs10091429	NRG1	Individual P-value = 0.5259 for SCZ , Individual P-value = 0.9077 for SCZ and BP		Negative
SZ	rs2439286	NRG1	Individual P-value = 0.6369 for SCZ , Individual P-value = 0.5518 for SCZ and BP		Negative
SZ	rs2439300	NRG1	Individual P-value = 0.4052 for SCZ , Individual P-value = 0.9469 for SCZ and BP		Negative
SZ	rs1948098	NRG1	Individual P-value = 0.3353 for SCZ , Individual P-value = 0.3572 for SCZ and BP		Negative
SZ	rs2347501	NRG1 NRG1-IT3	Individual P-value = 0.5084 for SCZ , Individual P-value = 0.5315 for SCZ and BP		Negative
SZ	rs1503491	NRG1	Individual P-value = 0.609 for SCZ , Individual P-value = 0.7019 for SCZ and BP		Negative
SZ	rs1545961	NRG1	Individual P-value = 0.3823 for SCZ , Individual P-value = 0.1336 for SCZ and BP		Negative
SZ	rs1481762	NRG1 NRG1-IT1	Individual P-value = 0.5544 for SCZ , Individual P-value = 0.5402 for SCZ and BP		Negative
SZ	rs1487141	NRG1	Individual P-value = 0.9662 for SCZ , Individual P-value = 0.8195 for SCZ and BP		Negative
SZ	rs10954842	NRG1	Individual P-value = 0.7634 for SCZ , Individual P-value = 0.9317 for SCZ and BP		Negative
SZ	rs1481747	NRG1	Individual P-value = 0.7276 for SCZ , Individual P-value = 0.9216 for SCZ and BP		Negative
SZ	rs10503932	NRG1	Individual P-value = 0.566 for SCZ , Individual P-value = 0.494 for SCZ and BP		Negative
SZ	rs10954811	NRG1	Individual P-value = 0.6247 for SCZ , Individual P-value = 0.8101 for SCZ and BP		Negative
SZ	rs10103750	NRG1	Individual P-value = 0.2753 for SCZ , Individual P-value = 0.6566 for SCZ and BP		Negative
SZ	rs10113797	NRG1	Individual P-value = 0.1911 for SCZ , Individual P-value = 0.1981 for SCZ and BP		Negative
SZ	rs10095694	NRG1	Individual P-value = 0.0087 for SCZ , Individual P-value = 0.006 for SCZ and BP	This marker is nominally significant in the combined sample	Positive
SZ	rs10096770	NRG1	Individual P-value = 0.9176 for SCZ , Individual P-value = 0.5636 for SCZ and BP		Negative
SZ	rs6468099	NRG1	Individual P-value = 0.7519 for SCZ , Individual P-value = 0.5716 for SCZ and BP		Negative
SZ	rs553950	NRG1	Individual P-value = 0.0288 for SCZ , Individual P-value = 0.0109 for SCZ and BP	This SNP is nominally significant in all three groups: BP, SCZ and combined.	Positive
SZ	rs6988339	NRG1	Individual P-value = 0.0103 for SCZ , Individual P-value = 0.0058 for SCZ and BP	This marker is nominally significant in the combined sample	Positive
SZ	rs6986716	NRG1	Individual P-value = 0.991 for SCZ , Individual P-value = 0.5832 for SCZ and BP		Negative
SZ	rs7015249	NRG1	Individual P-value = 0.1964 for SCZ , Individual P-value = 0.3427 for SCZ and BP		Negative
SZ	rs7007662	NRG1 NRG1-IT1	Individual P-value = 0.7023 for SCZ , Individual P-value = 0.7981 for SCZ and BP		Negative
SZ	rs901561	NRG1	Individual P-value = 0.7958 for SCZ , Individual P-value = 0.9163 for SCZ and BP		Negative
SZ	rs726908	NRG1	Individual P-value = 0.6665 for SCZ , Individual P-value = 0.5578 for SCZ and BP		Negative
SZ	rs2919390	NRG1	Individual P-value = 0.0096 for SCZ , Individual P-value = 0.0105 for SCZ and BP	This marker is nominally significant in the combined sample	Positive
SZ	rs2439305	NRG1	Individual P-value = 0.6679 for SCZ , Individual P-value = 0.752 for SCZ and BP		Negative
SZ	rs3757930	NRG1	Individual P-value = 0.2035 for SCZ , Individual P-value = 0.1164 for SCZ and BP		Negative
SZ	rs327329	NRG1	Individual P-value = 0.4418 for SCZ , Individual P-value = 0.7353 for SCZ and BP		Negative
SZ	rs4513929	NRG1	Individual P-value = 0.4213 for SCZ , Individual P-value = 0.9227 for SCZ and BP		Negative
SZ	rs4298458	NRG1	Individual P-value = 0.6152 for SCZ , Individual P-value = 0.9032 for SCZ and BP		Negative
SZ	rs4733140	NRG1	Individual P-value = 0.6035 for SCZ , Individual P-value = 0.8239 for SCZ and BP		Negative
SZ	rs4733132	NRG1	Individual P-value = 0.5628 for SCZ , Individual P-value = 0.2859 for SCZ and BP		Negative
SZ	rs9656744	NRG1	Individual P-value = 0.8711 for SCZ , Individual P-value = 0.5984 for SCZ and BP		Negative
SZ	rs9886497	NRG1	Individual P-value = 0.2086 for SCZ , Individual P-value = 0.2653 for SCZ and BP		Negative

Haplotypes reported by this study for SZ/MDD

Disease	Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Description	Result Category
SZ	rs2919390 - rs6988339		NRG1	P-value = 0.0012 for SZ, P-value = 0.0008 for SCZ and BP		Positive
SZ	rs2439286 - rs10095694 - rs2919390		NRG1	P-value = 0.0017 for SCZ and BP		Positive
SZ	rs2919390 - rs6988339 - rs3757930		NRG1	P-value = 0.0001 for SZ, P-value = 0.0001 for SCZ and BP	the most significant haplotype in SCZ was also nominally significant in the BP sample; this was the only haplotype to withstand permutation analysis in this study, identifying a new region of association with both schizophrenia and the combined case group in the Scottish population	Positive
SZ	rs2439286 - rs10095694 - rs2919390 - rs6988339		NRG1	P-value = 0.0003 for SZ, P-value = 0.0002 for SCZ and BP		Positive
SZ	rs1503491 - rs553950 - rs327329 - rs7007662		NRG1	P-value = 0.0007 for SZ, P-value = 0.0029 for SZ and BP combined		Positive
SZ	rs2439300 - rs2439286 - rs10095694 - rs2919390		NRG1	P-value = 0.0097 for SZ and BP combined		Positive
SZ	rs2439305 - rs2439300 - rs2439286 - rs10095694		NRG1	P-value = 0.0098 for SZ and BP combined		Positive
SZ	rs2439286 - rs10095694		NRG1	P-value = 0.0037 for SZ, P-value = 0.0028 for SCZ and BP		Positive
SZ	rs553950 - rs327329 - rs7007662 - rs1481762		NRG1	P-value = 0.0167 for SZ, P-value = 0.0145 for SZ and BP combined		Positive
SZ	rs1503491 - rs553950		NRG1	P-value = 0.0243 for SZ, P-value = 0.0117 for SZ and BP combined		Positive
SZ	rs6988339 - rs3757930		NRG1	P-value = 0.0014 for SZ, P-value = 0.0004 for SCZ and BP		Positive
SZ	rs1503491 - rs553950 - rs327329	T-T-T	NRG1	P-value = 0.0003 for SZ, P-value = 0.0017 for SZ and BP combined	3-SNP haplotype is nominally significant with SCZ alone, but it does not withstand permutation analysis	Positive
SZ	rs2919390 - rs6988339 - rs3757930 - rs10103750		NRG1	P-value = 0.0003 for SZ, P-value = 0.0001 for SCZ and BP		Positive
SZ	rs10954811 - rs1503491 - rs553950		NRG1	P-value = 0.0146 for SZ, P-value = 0.0078 for SZ and BP combined		Positive
SZ	rs553950 - rs327329 - rs7007662		NRG1	P-value = 0.0099 for SZ, P-value = 0.0034 for SZ and BP combined		Positive
SZ	rs10954811 - rs1503491 - rs553950 - rs327329		NRG1	P-value = 0.0003 for SZ, P-value = 0.0018 for SZ and BP combined		Positive
SZ	rs10095694 - rs2919390 - rs6988339 - rs3757930		NRG1	P-value = 0.0003 for SZ, P-value = 0.0003 for SCZ and BP		Positive
SZ	rs10113797 - rs10954811 - rs1503491 - rs553950		NRG1	P-value = 0.0071 for SZ and BP combined		Positive
SZ	rs6988339 - rs3757930 - rs10103750		NRG1	P-value = 0.002 for SZ, P-value = 0.0005 for SCZ and BP		Positive
SZ	rs10095694 - rs2919390		NRG1	P-value = 0.002 for SZ, P-value = 0.0016 for SCZ and BP		Positive
SZ	rs6988339 - rs3757930 - rs10103750 - rs10503932		NRG1	P-value = 0.0048 for SZ, P-value = 0.002 for SCZ and BP		Positive
SZ	rs10095694 - rs2919390 - rs6988339		NRG1	P-value = 0.0002 for SZ, P-value = 0.0002 for SCZ and BP		Positive

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Result Category
SZ	NRG1 SNP8NRG241930	NRG1	point mutation	Individual P-value = 0.6237 for SCZ , Individual P-value = 0.8147 for SCZ and BP	Negative
SZ	NRG1 SNP8NRG221533	NRG1	point mutation	Individual P-value = 0.7189 for SCZ , Individual P-value = 0.7929 for SCZ and BP	Negative
SZ	NRG1 SNP8NRG221132	NRG1	point mutation	Individual P-value = 0.994 for SCZ , Individual P-value = 0.7566 for SCZ and BP	Negative
SZ	NRG1 SNP8NRG243177	NRG1	point mutation	Individual P-value = 0.8945 for SCZ , Individual P-value = 0.5341 for SCZ and BP	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	NRG1	Our study identifies a new of NRG1 region involved in schizophrenia and bipolar disorder in the Scottish population.	Positive