The top 20 interaction terms after case-control studies in RS-I, RS-II and RS-III separate and combined.

<p>The interactions are sorted based on the <i>p</i>-value of the β_int after the case-control study in the combined data set of RS-I, RS-II and RS-III. The HDL levels are adjusted for sex and age, the residuals are not scaled around zero. Number of cases: 416 (RS-I), 244 (RS-II) and 447 (RS-III). Number of controls: 2996 (RS-I), 1602 (RS-II) and 1621 (RS-III). *1–*4 mark the interaction terms that are in high LD with each other: <i>R</i>²>0.913.</p><p>The top 20 interaction terms after case-control studies in RS-I, RS-II and RS-III separate and combined.</p

The forest plots for β_int of the four most significant interaction terms after meta-analysis of the replication cohorts: rs2315598-rs2853228 (a), rs6848132-rs7863451 (b), rs3756856-rs11758333 (c) and rs4596126-rs11676467 (d).

<p>Although the analysis in the discovery and the filtering was done with scaled phenotypes, for these forest plots, the HDL levels are not scaled in the Rotterdam Study cohorts.</p

The overlap between the interaction terms with <i>p</i>-value<3.03 · 10⁻⁷ after a GWIS with GLIDE in RS-I only and after a GWIS with GLIDE in RS-I, RS-II and RS-III combined.

<p>The overlap between the interaction terms with <i>p</i>-value<3.03 · 10⁻⁷ after a GWIS with GLIDE in RS-I only and after a GWIS with GLIDE in RS-I, RS-II and RS-III combined.</p

The smallest detectable effect with the current sample size of 2,996 individuals at 80% (a), 50% (b) and 1% (c) power levels.

<p>The smallest detectable effect with the current sample size of 2,996 individuals at 80% (a), 50% (b) and 1% (c) power levels.</p

Flow diagram overview of the analysis plan.

<p>Flow diagram overview of the analysis plan.</p

The top 20 interaction terms after replication.

<p>The interactions are sorted based on the <i>p</i>-value of the interaction term β_int. The HDL levels are adjusted for sex and age. The phenotypes of the Rotterdam Study are not scaled around zero.</p><p>*Interaction terms in LD with each other (<i>R</i>²>0.872).</p><p>**order of the directions: AGES, ARIC, CHS, ERF, FHS, NFBC-66, RS-I, RS-II, RS-III. The meta-analysis was done with fixed effects.</p><p>The top 20 interaction terms after replication.</p

Baseline characteristics for discovery and replication cohorts.

<p>Baseline characteristics for discovery and replication cohorts.</p

Novel loci for glycaemic and obesity-related traits achieving genome-wide significance (<i>p</i><5x10^-8).

<p>Novel loci for glycaemic and obesity-related traits achieving genome-wide significance (<i>p</i><5x10^-8).</p

Broad category functional annotation (A) and cell-type specific annotation (B) of credible set variants.

<p>On the x-axis is each category of broad functional annotation (A) or cell-type specific annotation (B). The fraction of credible set variants that overlap with each category is shown on y-axis. The overlapping variants are further broken down into either variants that exist in both the 1000 Genomes and HapMap reference panel (green) or those that exist only in the 1000 Genomes reference panel (red). TFBS, transcription factor binding site; ncRNA, non-coding RNA; UTR, untranslated regions; GM12878, lymphoblastoid cell line from European ancestry female; hESC, H1 human embryonic stem cells; hASC(t1), human pre-adipocytes; hASC(t4), mature human adipocytes; HepG2, liver carcinoma cell-line; HMEC, human mammary epithelial cells; HSMM, human skeletal muscle myoblasts; HUVEC, human umbilical vein endothelial cells; K562, human myelogenous leukemia cell-line; NHEK, normal human epidermal keratinocytes; NHLF, normal human lung fibroblasts.</p

Loci with multiple distinct signals of association with glycaemic and obesity-related traits achieving “locus-wide” significance in conditional analysis (<i>p</i>_COND<10⁻⁵).

<p>Loci with multiple distinct signals of association with glycaemic and obesity-related traits achieving “locus-wide” significance in conditional analysis (<i>p</i>_COND<10⁻⁵).</p