Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression.
View Article and Find Full Text PDFIn the era of personalized medicine with more and more patient-specific targeted therapies being used, we need reliable, dynamic, faster and sensitive biomarkers both to track the causes of disease and to develop and evolve therapies during the course of treatment. Metabolomics recently has shown substantial evidence to support its emerging role in disease diagnosis and prognosis. Aside from biomarkers and development of therapies, it is also an important goal to understand the involvement of mitochondrial DNA (mtDNA) in metabolic regulation, aging and disease development.
View Article and Find Full Text PDFHistorical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population.
View Article and Find Full Text PDFWe investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (n = 4), genotyping by genome-wide SNP array (n = 34) and whole-genome sequencing (n = 12). We performed genome-wide linkage analysis, family-based association analysis and polygenic risk score estimates.
View Article and Find Full Text PDFNumerous predictive models for the risk of type 2 diabetes mellitus (T2DM) exist, but a minority of them has implemented nutrition data so far, even though the significant effect of nutrition on the pathogenesis, prevention and management of T2DM has been established. Thus, in the present study, we aimed to build a predictive model for the risk of T2DM that incorporates nutrition data and calculates its predictive performance. We analysed cross-sectional data from 1591 individuals from the population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013-14) and used a bootstrap enhanced elastic net penalised multivariate regression method in order to build our predictive model and select among 193 food intake variables.
View Article and Find Full Text PDFPsychosis is a highly heritable and heterogeneous psychiatric condition. Its genetic architecture is thought to be the result of the joint effect of common and rare variants. Families with high prevalence are an interesting approach to shed light on the rare variant's contribution without the need of collecting large cohorts.
View Article and Find Full Text PDFIt has been suggested that mitochondrial dysfunction has an influence on lipid metabolism. The fact that mitochondrial defects can be accumulated over time as a normal part of aging may explain why cholesterol levels often are altered with age. To test the hypothesis whether mitochondrial variants are associated with lipid profile (total cholesterol, LDL, HDL, and triglycerides) we analyzed a total number of 978 mitochondrial single nucleotide polymorphisms (mtSNPs) in a sample of 2,815 individuals participating in the population-based KORA F4 study.
View Article and Find Full Text PDFIt has been suggested that mitochondrial dysfunction plays a role in metabolic disorders including obesity, diabetes, and hypertension. The fact that mitochondrial defects can be accumulated over time as a normal part of aging may explain why some individuals can eat all sorts of foods and remain at normal weight while they are young. However, around the fourth decade of life there is a trend towards "middle-age spread" with weight gain and the body's decreasing ability to metabolize calories efficiently.
View Article and Find Full Text PDFIt has been suggested that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To test whether mitochondrial variants influence the risk of asthma, we analyzed 16,158 mtSNPs in a sample of 372 asthmatic children and 395 healthy children using the DNA pooling technique and genome wide association analysis. Stratified analysis by sex was performed to explain the differences observed between sexes in the etiology of asthma.
View Article and Find Full Text PDFBackground: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic.
View Article and Find Full Text PDFBackground: In the last years GWA studies have successfully identified common SNPs associated with complex diseases. However, most of the variants found this way account for only a small portion of the trait variance. This fact leads researchers to focus on rare-variant mapping with large scale sequencing, which can be facilitated by using linkage information.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
July 2010
We present the findings of a linkage study of bipolar affective disorder (BPAD) that involve the pseudoautosomal region 1 of the human sex chromosomes. We analyzed a substantial subset of pedigrees (89 families of German and Spanish origin; 661 participants; 298 affected individuals) from the large collection of BPAD-affected families with which a genomewide linkage analysis was previously performed and where the pseudoautosomal regions were poorly covered. Nonparametric linkage (Z(lr)) scores were calculated.
View Article and Find Full Text PDFObjectives: Accurate sex-specific genetic maps are essential for gene mapping projects when using multipoint methods, especially for the pseudoautosomal regions (PARs). This paper describes a new sex-specific genetic map for the human PARs.
Methods: We used multipoint linkage analysis, three-generation pedigrees and to date, the largest set of genetic markers to estimate recombination events in the PARs.
Background: With the beginning of the era of genome-wide association studies methods to obtain 'in silico' genotypes have gained importance. In this context, an evaluation of genome-wide power levels of current marker panels and the power gain achievable with imputed genotypes are of high interest.
Methods: Power for single-marker analysis of imputed genotypes is evaluated via a simulation study based on HapMap data.
A role of ATP13A2 in early-onset Parkinsonism (EOP) has been proposed. Conversely, the contribution of this ATPase to late-onset Parkinson's disease (PD) remains unexplored. We therefore conducted a case-control association study in this age-of-onset group with PD.
View Article and Find Full Text PDFWe carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)).
View Article and Find Full Text PDFAge-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data.
View Article and Find Full Text PDFTwo intervals of sequence identity at the tips of X and Y chromosomes, the human pseudoautosomal regions PAR1 and PAR2, have drawn interest from researchers in human genetics, cytogenetics, and evolutionary biology. However, they have been widely ignored in linkage and association studies. The pseudoautosomal regions (PARs) pair and recombine during meiosis like autosomes, but the recombination activity in PAR1 is extremely different between sexes.
View Article and Find Full Text PDFAndrogenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent.
View Article and Find Full Text PDFAlopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis.
View Article and Find Full Text PDFAlcohol dependence is a typical example of a complex trait that is governed by several genes and for which the mode of inheritance is unknown. We analyzed the microsatellite markers and the Affymetrix single-nucleotide polymorphisms (SNPs) for a subset of the Collaborative Study on the Genetics of Alcoholism family sample, 93 pedigrees of Caucasian ancestry comprising 919 persons, 390 of whom are affected according to DSM III-R and Feighner criteria. In particular, we performed parametric single-marker linkage analysis using MLINK of the LINKAGE package (for the microsatellite data), as well as multipoint MOD-score analysis with GENEHUNTER-MODSCORE (for the microsatellite and SNP data).
View Article and Find Full Text PDFAm J Hum Genet
December 2005
We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.
View Article and Find Full Text PDFAndrogenetic alopecia (AGA), or male-pattern baldness, is the most common form of hair loss. Its pathogenesis is androgen dependent, and genetic predisposition is the major requirement for the phenotype. We demonstrate that genetic variability in the androgen receptor gene (AR) is the cardinal prerequisite for the development of early-onset AGA, with an etiological fraction of 0.
View Article and Find Full Text PDFAn investigation of the genetic influences on life span and survival was conducted among elderly African-Americans, Caribbean Hispanics, and Caucasians Medicare recipients (ages 65-104 years). Family history information on 13,161 parents and siblings was obtained. Heritability of life span varied by the age and by ethnic group being lowest for African-Americans.
View Article and Find Full Text PDF