Mean change in central retinal thickness.

<p>Effect of bevacizumab (n = 161, blue) versus ranbizumab (n = 166, red) on the change of retinal thickness over time. Data are presented as mean ±95% CI. A mixed linear model was used for this graph.</p

Adverse events by organ system.

<p>Adverse events by organ system.</p

Serious adverse events.

<p>Serious adverse events.</p

Outcome Measures at 12 months.

<p>Outcome Measures at 12 months.</p

In- and exclusion criteria.

<p>In- and exclusion criteria.</p

Baseline Characteristics.

<p>Baseline Characteristics.</p

Consort flow chart.

<p>Consort flow chart.</p

Mean change in BCVA from baseline.

<p>Mean change in BCVA per group. A mixed linear model was used for this graph. This type of analysis shows a mean gain of 5.9 letters in the bevacizumab group and a mean gain of 6.7 letters in the ranibizumab group (p = 0.56).</p

Rare and low-frequency coding variants alter human adult heigh

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways