Evidence of linkage and association on 18p11.2 for psychosis

Abstract

The genetic basis of bipolar disorder (BPD) and schizophrenia (SCZ) has been established through numerous clinical and molecular studies. Although often considered separate nosological entities, evidence now suggests that the two syndromes may share some genetic liability. Recent studies have used a composite phenotype (psychosis) that includes BPD, SCZ, psychosis not otherwise specified, and schizoaffective disorder, to identify shared susceptibility loci. Several chromosomal regions are reported to be shared between these syndromes (18p, 6q, 10p, 13q, 22q). As a part of our endeavor to scan these regions, we report a positive linkage and association finding at 18p11.2 for psychosis. Two-point linkage analysis performed on a series of 52 multiplex pedigrees with 23 polymorphic markers yielded a LOD score of 2.02 at D18S37. An independent set of 159 parent offspring trios was used to confirm this suggestive finding. The TDT analysis yielded support for association between the marker D18S453 and the disease allele (chi2 = 4.829, P < 0.028). This region has been implicated by several studies on BPD [Sjoholt et al. (2004); Mol Psychiatry 9(6):621-629; Washizuka et al. (2004); Biol Psychiatry 56(7):483-489; Pickard et al. (2005); Psychiatr Genet 15(1):37-44], SCZ [Kikuchi et al. (2003); J Med Dent Sci 50(3):225-229; Babovic-Vuksanovic et al. (2004); Am J Med Genet 124(3):318-322] and also as a shared region between the two diseases [Ishiguro et al. (2001); J Neural Transm 108(7):849-854; Reyes et al. (2002); Mol Psychiatry 7(4):337-339; Craddock et al. (2005); J Med Genet 42(3):193-204]. Our findings provide an independent validation of the above reports, and suggest the presence of susceptibility loci for psychoses in this region.

A genome-wide linkage study of bipolar disorder and co-morbid migraine: Replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11

“…The search was performed in pub med for every chromosome separately with the key words: “Bipolar disorder, genetics, linkage, chromosome 1…X” and “Migraine, genetics, linkage, chromosome 1…X”, Table 3 displays all linkage loci that have been significantly or suggestively found in migraine linkage studies (Gardner et al, 1997; Nyholt et al, 1998a,b, 2000; Jones et al, 2001; Carlsson et al, 2002; Wessman et al, 2002; Lea et al, 2002; Björnsson et al, 2003; Soragna et al, 2003; Cader et al, 2003; Nyholt et al, 2005; Russo et al, 2005; Lea et al, 2005; Anttila et al, 2006), and the bipolar linkage studies (Savitz et al, 2007; Jamra et al, 2007; Zandi et al, 2007; Goes et al, 2007; Cassidy et al, 2007; Kerner et al, 2007; Jones et al, 2007; Etain et al, 2006; Marcheco-Teruel et al, 2006; Tomàs et al, 2006; Mukherjee et al, 2006; Schumacher et al, 2005; Hamshere et al, 2005; Lambert et al, 2005; McQueen et al, 2005; Kealey et al, 2005; Lin et al, 2005; Macgregor et al, 2004; Middleton et al, 2004; Fallin et al, 2004; Curtis et al, 2003; McInnis et al, 2003; Willour et al, 2003; Ewald et al, 2003; Ekholm et al, 2003; Ewald et al, 2002; Ekholm et al, 2002; Bailer et al, 2002; Dick et al, 2002; Cichon et al, 2001; Kelsoe et al, 2001; Radhakrishna et al, 2001; Detera-Wadleigh et al, 1999; Morissette et al, 1999; Ginns et al, 1998; Ewald et al, 1998; Detera-Wadleigh et al, 1997; Edenberg et al, 1997; Blackwood et al, 1996; Turecki et al, 1995; Pekkarinen et al, 1995) that have demonstrated overlapping or closely related linkage to these migraine loci. In addition we compared linkage studies in BPAD to the identified genes in FHM, and the BPAD (Jamra et al, 2007; Zandi et al, 2007; Hamshere et al, 2005; Middleton et al, 2004; Fallin et al, 2004; …”

Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes

“…Some of the families in the cohort have been on follow up for longer than 10 years. We have previously noted evidence of linkage in psychosis at chromosome 18p11.2, and the sex‐specific association to the DISC1 gene using a case–control study design in samples taken from this cohort. For the current study, eight families (A through H) with high loading of SMI (SCZ, BD, and psychosis in the context of these eight pedigrees; Fig.…”

Regulation of pituitary adenylyl cyclase-activating polypeptide (PACAP, ADCYAP1: adenylyl cyclase-activating polypeptide 1) in the treatment of schizophrenia

“…Many studies reported that susceptibility genes may be present on chromosome 18p where the PACAP gene is located [86][87][88][89][90][91] . A possible linkage of certain psychiatric diseases with the PACAP gene Adcyap1 has been suggested.…”