Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires: lessons from a pilot study within FinnGen.

Objectives: To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.

Design: Biobank-based recontacting pilot study.

Setting: Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

The human genetic epidemiology of COVID-19.

Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different study designs and multiple disease phenotype definitions to identify several genomic regions associated with COVID-19. Along with a multitude of follow-up studies, these findings have increased our understanding of disease aetiology and provided routes for management of COVID-19.

Reduced reproductive success is associated with selective constraint on human genes.

Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants. Although genes under the strongest selective constraint are highly enriched for associations with Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known. Here we show that genetic variants that damage these genes are associated with markedly reduced reproductive success, primarily owing to increased childlessness, with a stronger effect in males than in females.

The contribution of X-linked coding variation to severe developmental disorders.

Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.

Common genetic variants contribute to risk of rare severe neurodevelopmental disorders.

There are thousands of rare human disorders that are caused by single deleterious, protein-coding genetic variants. However, patients with the same genetic defect can have different clinical presentations, and some individuals who carry known disease-causing variants can appear unaffected. Here, to understand what explains these differences, we study a cohort of 6,987 children assessed by clinical geneticists to have severe neurodevelopmental disorders such as global developmental delay and autism, often in combination with abnormalities of other organ systems.

Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury.

Objectives: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinical studies suggest that vitamin D status influences the recovery after TBI. However, there is no published clinical data on links between vitamin D status and TBI outcomes.