Suchergebnisse

AbstractAssociation studies, comparing elite athletes with sedentary controls, have reported a number of genes that may be related to athlete status. The present study reports the first genome wide linkage scan for athlete status. Subjects were 4488 adult female twins from the TwinsUK Adult Twin Registry (793 monozygotic [MZ] and 1000 dizygotic [DZ] complete twin pairs, and single twins). Athlete status was measured by asking the twins whether they had ever competed in sports and what was the highest level obtained. Twins who had competed at the county or national level were considered elite athletes. Using structural equation modeling in Mx, the heritability of athlete status was estimated at 66%. Seven hundred DZ twin pairs that were successfully genotyped for 1946 markers (736 microsatellites and 1210 SNPs) were included in the linkage analysis. Identical-by-descent probabilities were estimated in Merlin for a 1 cM grid, taking into account the linkage disequilibrium of correlated SNPs. The linkage scan was carried out in Mx using the-approach. Suggestive linkages were found on chromosomes 3q22-q24 and 4q31-q34. Both areas converge with findings from previous studies using exercise phenotypes. The peak on 3q22-q24 was found at the SLC9A9 gene. The region 4q31-q34 overlaps with the region for which suggestive linkages were found in two previous linkage studies for physical fitness (FABP2 gene; Bouchard et al., 2000) and physical activity (UCP1 gene; Simonen et al., 2003). Future association studies should further clarify the possible role of these genes in athlete status.

AbstractSusceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.

AbstractTwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King's College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several 'omic' technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the 'TwinsUK' resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.

Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene–environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol,rs2483058in an intron ofSRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P= 3.98 × 10−8). We followed up the association in further genotyped monozygotic twins (N= 1,261), which showed a moderate association for the variant (P= 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P= 4.03 × 10−8).