Association of genetic variants rs7759938 (upper panel) and rs314279 (lower panel) with adult metabolic profiles.

<p>All phenotypes were standardized prior to analyses. Two regression models were used: Model A including age as a covariate, and Model B including both the alternative SNP and age as covariates. Subjects using lipid lowering drugs or with lipid levels +/−5 standard deviations (SD) from the mean were excluded from the lipid/lipoprotein analysis. Only subjects with normal glucose tolerance not receiving treatment for diabetes were included in the regression analyses of glucose and serum insulin. The effect allele for both rs7759938 and rs314279 is C. ApoA1 =  Apolipoprotein A1, ApoB  =  Apolipoprotein B, FP  =  Fasting plasma. FS  =  Fasting serum, 2H glucose  =  Plasma glucose concentrations at 2 h after a 75 g oral glucose load. Participants of the oral glucose test were instructed to fast for 10 hours. ^# The variable was logarithm-transformed prior to the analysis.</p

Forest plot of the effect of F_ROHLD on height.

<p>Results of a meta-analysis of the association between F_ROHLD and height are shown for twenty-one population samples. The model was adjusted for age and sex in all samples. Additionally, it was adjusted for genomic kinship in samples with pairs of related individuals (CROATIA-Korčula, CROATIA-Split, CROATIA-Vis, ERF, FINRISK, HBCS, H2000, INGI-CARL, INGI-FVG, INGI-VB, MICROS, NFBC1966, NSPHS, ORCADES and YFS). The plot shows estimated effect sizes (solid squares) for each population, with 95% confidence intervals (horizontal lines). Each sample estimate is weighted by the inverse of the squared standard error of the regression coefficient, so that the smaller the standard error of the study, the greater the contribution it makes to the pooled regression coefficient. The area of the solid squares is proportional to the weighting given to each study in the meta-analysis. Effect sizes in z-score units (with 95% confidence intervals) are: CROATIA-Korčula = −0.02 (−0.09, 0.04); CROATIA-Split = −0.06 (−0.1, −0.002); CROATIA-Vis = −0.07 (−0.1, −0.01); EGCUT = −0.09 (−0.04, 0.2); ERF = −0.08 (−0.1, −0.05); FINRISK = −0.1 (−0.2, −0.07); HBCS = −0.04 (−0.2, 0.1); H2000 = −0.2 (−0.5, 0.04); INGI-CARL = 0.02 (−0.03, 0.07); INGI-FVG = −0.0001 (−0.08, 0.08); INGI-VB = 0.005 (−0.03, 0.04); LBC1921 = −0.1 (−0.3, 0.04); LBC1936 = 0.2 (−0.1, 0.4); MICROS = −0.06 (−0.08, −0.05); NFBC1966 = −0.1 (−0.2, −0.1); NSPHS = −0.07 (−0.07, −0.06); ORCADES = −0.04 (−0.08, 0.001); QIMR = −0.07 (−0.5, 0.3); RS = −0.02 (−0.1, 0.08); SOCCS = −0.05 (−0.4, 0.3); YFS = −0.3 (−1.2, 0.7).</p

Sample details.

1<p>All data were analysed using Illumina SNP arrays. 300 refers to the Illumina HumanHap 300 panel, 370 to the Illumina HumanHap 370 Duo/Quad panels, 610 to the Illumina Human 610 Quad panel and 670 to the Illumina Human 670 Quad panel. In order to harmonise the data, the analysis was conducted using only those SNPs present in the HumanHap 300 panel.</p>2<p>Population-based studies.</p>3<p>Population-based studies in isolated populations.</p>4<p>Birth cohort studies.</p>5<p>Case control studies.</p

Three alternative measures of mean homozygosity, with 95% confidence intervals, by population sample.

<p>(A) shows mean F_ROH by population sample. F_ROH is defined as the percentage of the genotyped autosomal genome in ROH measuring at least 1.5 Mb. Mean values of F_ROH per population (with 95% confidence intervals) are: CROATIA-Korčula = 1.27 (1.18, 1.36); CROATIA-Split = 0.65 (0.59, 0.71); CROATIA-Vis = 0.94 (0.87,1.01); EGCUT = 0.56 (0.54, 0.58); ERF = 1.12 (1.04, 1.20); FINRISK = 0.79 (0.77, 0.82); HBCS = 0.63 (0.60, 0.65); H2000 = 0.84 (0.82, 0.86); INGI-CARL = 0.78 (0.65, 0.91); INGI-FVG = 1.49 (1.40, 1.58); INGI-VB = 0.76 (0.71, 0.81); LBC1921 = 0.30 (0.25, 0.35); LBC1936 = 0.26 (0.24, 0.28); MICROS = 0.93 (0.87, 0.99); NFBC1966 = 1.02 (1.00, 1.04); NSPHS = 2.83 (2.64, 3.02); ORCADES = 0.81 (0.75, 0.87); QIMR = 0.22 (0.21, 0.23); RS = 0.29 (0.28, 0.30); SOCCS = 0.30 (0.28, 0.32); YFS = 0.81 (0.79, 0.83). (B) shows mean F_ROHLD by population sample. F_ROHLD is defined as the percentage of the genotyped autosomal genome in ROH measuring at least 1.0 Mb, derived from a panel of independent SNPs. Mean values of F_ROHLD per population (with 95% confidence intervals) are: CROATIA-Korčula = 0.67 (0.61, 0.73); CROATIA-Split = 0.13 (0.11, 0.15); CROATIA-Vis = 0.48 (0.43, 0.53); EGCUT = 0.10 (0.09, 0.10); ERF = 0.53 (0.48, 0.58); FINRISK = 0.21 (0.20, 0.23); HBCS = 0.13 (0.11, 0.14); H2000 = 0.23 (0.22, 0.24); INGI-CARL = 0.44 (0.34, 0.54); INGI-FVG = 0.93 (0.86, 0.99); INGI-VB = 0.41 (037, 0.45); LBC1921 = 0.05 (0.02, 0.09); LBC1936 = 0.02 (0.01, 0.03); MICROS = 0.47 (0.43, 0.51); NFBC1966 = 0.32 (0.31, 0.33); NSPHS = 1.17 (1.07, 1.27); ORCADES = 0.35 (0.31, 0.39); QIMR = 0.013 (0.011, 0.015); RS = 0.04 (0.01, 0.07); SOCCS = 0.03 (0.02, 0.04); YFS = 0.20 (0.19, 0.21). (C) shows mean F_hom by population sample. F_hom is defined as the percentage of genotyped autosomal SNPs that are homozygous. Mean values of F_hom per population (with 95% confidence intervals) are: CROATIA-Korčula = 65.47 (65.43, 65.51); CROATIA-Split = 65.28 (65.25, 65.31); CROATIA-Vis = 65.61 (65.58, 65.64); EGCUT = 65.69 (65.68, 65.70); ERF = 65.32 (65.29, 65.35); FINRISK = 65.25 (65.23, 65.27); HBCS = 65.13 (65.12, 65.14); H2000 = 65.24 (65.23, 65.25); INGI-CARL = 65.20 (65.14, 65.26); INGI-FVG = 65.53 (65.49, 65.57); INGI-VB = 65.18 (65.16, 65.20); LBC1921 = 65.00 (64.97, 65.03); LBC1936 = 65.00 (64.99, 65.01); MICROS = 65.26 (65.23, 65.29); NFBC1966 = 65.27 (65.26, 65.28); NSPHS = 66.09 (66.01, 66.17); ORCADES = 65.37 (65.34, 65.40); QIMR = 64.75 (64.74, 64.76); RS = 65.00 (64.99, 65.01); SOCCS = 64.97 (64.95, 64.99); YFS = 65.26 (65.25, 65.27).</p

Forty-four WHR_adjBMI loci showing significant sex-differences.

<p>Chr: Chromosome; Pos: position; EAF: Effect Allele Frequency; EA: Effect allele; OA: Other allele</p><p>^a ‘Yes’ if the locus is mentioned as WHR_adjBMI locus for the first time</p><p>^b ‘Yes’ if the sex-difference in the effect on WHR_adjBMI is reported for the first time</p><p>^c Effect allele is according to the WHR_adjBMI increasing allele according to the associated sex.</p><p>The table shows the sex-specific (age-group combined) results, ordered by largest, positive effect in women to largest, negative effect in women. The age- and sex-specific results (four strata), more detailed information on the loci and on the screens for which they were detected are given in <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.s021" target="_blank">S5 Table</a></b>.</p

Age-dependent BMI loci.

<p>Effect estimates (beta ±95CI) per standard deviation in BMI and risk allele for loci showing age-differences in men & women ≤50y compared to men & women >50y. Loci are ordered by greater magnitude of effect in men & women ≤50y compared to men & women >50y. (95%CI: 95% confidence interval; BMI: body mass index; SD: standard deviation, *Newly identified loci).</p