Nash MW, Huezo-Diaz P, Williamson RJ, Sterne A, Purcell S, Hoda F et al. Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships. Hum Mol Genet 13: 2173-2182

MRC Social, Genetic and Developmental Psychiatry Research Centre, Section of Epidemiology, Institute of Psychiatry, King's College, London, UK.
Human Molecular Genetics (Impact Factor: 6.39). 11/2004; 13(19):2173-82. DOI: 10.1093/hmg/ddh239
Source: PubMed


There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34,371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller--but statistically powerful--sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.

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    • "Most studies indicate little evidence for association of this locus as confirmed by a meta-analysis of the marker SNP rs6295 (Ló pez-Leó n et al. 2008). The serotonin receptor 1B gene (HTR1B) maps to human chromosome 6q13, a region for which sex-specific (male) linkage to depression and/or anxiety has been reported (Holmans et al. 2004 ; Nash et al. 2004). The variant G861C (rs6296) is a functional polymorphism (Maura et al. 1993) ; however, no significant association has been found directly with MDD although it has been suggested that rs6296 may only be associated with a more severe (i.e. "
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    • "Briefly, depression cases (18 years or older) of Caucasian origin with a recurrent depressive disorder were recruited from 3 sites in the UK (London, Cardiff and Birmingham). Control subjects were selected from the UK general practice based GENESiS study [21] and were included in the study if they were of Caucasian origin with no past or current psychiatric disorder. All subjects gave written informed consent. "
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    ABSTRACT: Migraine is a common disorder that often coexists with depression. While a functional polymorphism in methyleneterahydrofolate reductase gene (MTHFR C677T) has been implicated in depression; the evidence to support an association of MTHFR with migraine has been inconclusive. We aim to investigate the effect of this variant on propensity for migraine and to perform a systematic review and meta-analysis of studies of MTHFR and migraine to date. Individuals with migraine (n = 447) were selected from the Depression Case Control (DeCC) study to investigate the association between migraine and MTHFR C677T single nucleotide polymorphism (SNP) rs1801133 using an additive model compared to non-migraineurs adjusting for depression status. A meta-analysis was performed and included 15 studies of MTHFR and migraine. MTHFR C677T polymorphism was associated with migraine with aura (MA) (OR 1.31, 95% CI 1.01-1.70, p = 0.039) that remained significant after adjusting for age, sex and depression status. A meta-analysis of 15 case-control studies showed that T allele homozygosity is significantly associated with MA (OR = 1.42; 95% CI, 1.10-1.82) and total migraine (OR = 1.37; 95% CI, 1.07-1.76), but not migraine without aura (OR = 1.16; 95% CI, 0.36-3.76). In studies of non-Caucasian population, the TT genotype was associated with total migraine (OR= 3.46; 95% CI, 1.22-9.82), whereas in studies of Caucasians this variant was associated with MA only (OR = 1.28; 95% CI, 1.002-1.63). MTHFR C677T is associated with MA in individuals selected for depression study. A meta-analysis of 15 studies supports this association and demonstrated effects across ethnic groups.
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    • "Several genetic studies of neuroticism not involving the advance specification of candidate genes also have been conducted. Genome-wide linkage studies, which use large numbers of markers selected from across the genome to examine patterns of inheritance within families, have not yielded consistent findings (Fullerton et al., 2003; Nash et al., 2004), perhaps partly because of limitations in the statistical power of linkage studies (Risch & Merikangas, 1996). A more powerful recent genome-wide association study of unrelated individuals failed to find significant associations between single nucleotide polymorphisms (SNPs) and neuroticism (Shifman et al., 2008), but another recent study found associations of neuroticism and SNPs in MAMDC1 (van den Oord et al., 2008). "
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