Suchergebnisse

The Avera Twin Register (ATR) aims to study environmental and genetic influences on health and disease using a longitudinal repository of biological specimens, survey data, and health information provided by multiples and their family members. The ATR is located in Sioux Falls, South Dakota, which is a rural and frontier area in the Midwestern United States with a density of four people per square kilometer. The target area of the ATR is South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota, and Nebraska. Enrollment of twins and higher-order multiples of all ages and their family members started on May 18, 2016. A description of the first 13 months of enrollment in this longitudinal register will be provided. The ATR will collect longitudinal data on lifestyle, including diet and activity levels, aging, complex traits, and diseases. Upon registration, all participants are genotyped on the Illumina Global Screening Array (GSA) and twins and higher order multiples receive information on their zygosity. The ATR aims to contribute to large international GWAS consortia and collaborates closely with the Netherlands Twin Register, allowing for the comparison of collected data and analyses of results. In addition, the ATR will address twin-specific questions.

We identified the genetic variants for eye color by Genome-Wide Association Study (GWAS) in a Dutch Caucasian family-based population sample and examined the genetic correlation between hair and eye color using data from unrelated participants from the Netherlands Twin Register. With the Genome-wide Complex Trait Analysis software package, we found strong genetic correlations between various combinations of hair and eye colors. The strongest positive correlations were found for blue eyes with blond hair (0.87) and brown eyes with dark hair (0.71), whereas blue eyes with dark hair and brown eyes with blond hair showed the strongest negative correlations (-0.64 and -0.94, respectively). Red hair with green/hazel eyes showed the weakest correlation (-0.14). All analyses were corrected for age and sex, and we explored the effects of correcting for principal components (PCs) that represent ancestry and describe the genetic stratification of the Netherlands. When including the first three PCs as covariates, the genetic correlations between the phenotypes disappeared. This is not unexpected since hair and eye colors strongly indicate the ancestry of an individual. This makes it difficult to separate the effects of population stratification and the true genetic effects of variants on these particular phenotypes.

AbstractThe aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members' biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.

AbstractTwin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FSTvalues) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.

Objective: The human gut microbiota has been demonstrated to be associated with a number of host phenotypes, including obesity and a number of obesity-associated phenotypes. This study is aimed at further understanding and describing the relationship between the gut microbiota and obesity-associated measurements obtained from human participants. Subjects/Methods: Here, we utilize genetically informative study designs, including a four-corners design (extremes of genetic risk for BMI and of observed BMI; N = 50) and the BMI monozygotic (MZ) discordant twin pair design (N = 30), in order to help delineate the role of host genetics and the gut microbiota in the development of obesity. Results: Our results highlight a negative association between BMI and alpha diversity of the gut microbiota. The low genetic risk/high BMI group of individuals had a lower gut microbiota alpha diversity when compared to the other three groups. Although the difference in alpha diversity between the lean and heavy groups of the BMI-discordant MZ twin design did not achieve significance, this difference was observed to be in the expected direction, with the heavier participants having a lower average alpha diversity. We have also identified nine OTUs observed to be associated with either a leaner or heavier phenotype, with enrichment for OTUs classified to the Ruminococcaceae and Oxalobacteraceae taxonomic families. Conclusion: Our study presents evidence of a relationship between BMI and alpha diversity of the gut microbiota. In addition to these findings, a number of OTUs were found to be significantly associated with host BMI. These findings may highlight separate subtypes of obesity, one driven by genetic factors, the other more heavily influenced by environmental factors.

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10−8) and gene-based (p = 1.48 × 10−7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.

AbstractHere we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.

AbstractThe Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources — the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping — allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.

With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individuals age. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP) micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data). Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (R2 > 99%) between co-twins from 43 MZ pairs. For 75 dizygotic (DZ) pairs, R2 was ≈65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (R2 ≈ 90%) and duplications (R2 ≈ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (R2 ≈ 50–60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.