No abstract

Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or recessive models. Of special interest are a missense variant in LOXHD1 (MAF = 1.96%) and a tandem duplication in FBF1 covering 4 exons (MAF = 0.22%) associating with ARHI (OR = 3.7 for homozygotes, P = 1.7 × 10−22 and OR = 4.2 for heterozygotes, P = 5.7 × 10−27, respectively). We constructed an ARHI genetic risk score (GRS) using common variants and showed that a common variant GRS can identify individuals at risk comparable to carriers of rare high penetrance variants. Furthermore, we found that ARHI and tinnitus share genetic causes. This study sheds a new light on the genetic architecture of ARHI, through several rare variants in both Mendelian deafness genes and genes not previously linked to hearing.

Background: General practice systems in the Nordic countries share certain common features. The sector is based on the Nordic model of a tax-financed supply of services with a political objective of equal access for all. The countries also share the challenges of increased political expectations to deliver primary prevention and increased workload as patients from hospital care are discharged earlier. However, within this common framework, primary care is organized differently. This is particularly in relation to the private-public mix, remuneration systems and the use of financial and non-financial incentives. Objective: The objective of this paper is to compare the differences and similarities in primary care among the Nordic countries, to create a mapping of the future plans and reforms linked to remuneration and incentives schemes, and to discuss the pros and cons for these plans with reference to the literature. An additional objective is to identify gaps in the literature and future research opportunities. Results/Conclusions: Despite the many similarities within the Nordic health care systems, the primary care sectors function under highly different arrangements. Most important are the differences in the gate-keeping function, private versus salaried practices, possibilities for corporate ownership, skill-mix and the organisational structure. Current reforms and political agendas appear to focus on the side effects of the individual countries’ specific systems. For example, countries with salaried systems with geographical responsibility are introducing incentives for private practice and more choices for patients. Countries with systems largely based on private practice are introducing more monitoring and public regulation to control budgets. We also see that new governments tends to bring different views on the future organisation of primary care, which provide considerable political tension but few actual changes. Interestingly, Sweden appears to be the most innovative in relation to introducing new incentive schemes, perhaps because decisions are made at a more decentralised level.Published: April 2016.

Only examining mortality effects of society-wide economic conditions may understate the overall effect on cardiovascular health.

Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10 −8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.