Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts.

There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091).

Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time.

Activated partial thromboplastin time (aPTT) is associated with risk of thrombosis and coagulation disorders. We conducted a genome-wide association study for aPTT and identified significant associations with SNPs in three coagulation cascade genes, F12 (rs2731672, combined p = 2.16 x 10(-30)), KNG1 (rs710446, combined p = 9.

Variation in the uric acid transporter gene (SLC2A9) and memory performance.

Understanding human cognitive ageing is important to improve the health of an increasing elderly population. Serum uric acid levels have been linked to many ageing illnesses and are also linked to cognitive functioning, though the direction of the association is equivocal. SLC2A9, a urate transporter, influences uric acid levels.

White matter integrity in the splenium of the corpus callosum is related to successful cognitive aging and partly mediates the protective effect of an ancestral polymorphism in ADRB2.

It has recently been reported that the evolutionarily ancestral alleles of two functional polymorphisms in the beta(2)-adrenergic receptor gene (ADRB2) were related to higher cognitive ability in the 70 year old participants of the Lothian Birth Cohort 1936 (LBC1936). One emerging important factor in cognitive aging is the integrity of white matter tracts in the brain. Here, we used diffusion tensor MRI-based tractography to assess the integrity of eight white matter tracts in a subsample of the LBC1936.

Association of existing and new candidate genes for anxiety, depression and personality traits in older people.

Genetic variants that have previously been associated with personality traits and/or psychological distress, or inflammatory marker levels were investigated for their relationship to self-rated personality traits, anxiety, and depression in two elderly Scottish cohorts. Ten genes (29 SNPs) were investigated in the Lothian Birth Cohort 1936 (approximately 70 years, N = 1,091). Four of these genes and seven others (35 SNPs) were tested in the Lothian Birth Cohort 1921 who were measured on the same traits and states on two occasions (approximately 80 years, N = 550; 87 years, N = 229).

Age-associated cognitive decline.

Introduction: Age-associated cognitive decline-or normal (non-pathological, normative, usual) cognitive ageing-is an important human experience which differs in extent between individuals. The determinants of the differences in age-related cognitive decline are not fully understood. Progress in the field is taking place across many areas of biomedical and psychosocial sciences.

Selected summaries from the XVI World Congress of Psychiatric Genetics, Osaka, Japan, 11-15 October 2008.

The XVI World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics took place in Osaka, Japan, October 2008. Approximately 600 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illnesses, including schizophrenia, bipolar disorder, major depression, alcohol and drug abuse, autism, and attention-deficit disorder. Recently, the field has advanced considerably and includes new genome-wide association studies with the largest numbers of individuals screened and density of markers to date, as well as newly uncovered genetic phenomena, such as copy number variation that may prove to be relevant for specific brain disorders.

A case-control association study and family-based expression analysis of the bipolar disorder candidate gene PI4K2B.

Bipolar disorder, schizophrenia and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15-p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study.

A Functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly.

Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species.

Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

Background: Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22).