Longitudinal characteristics of the MDC Study participants (N = 2,943).

<p>BMI - body mass index; HDL-C - high density lipoprotein cholesterol; IQR - interquartile range; LDL-C - low density lipoprotein cholesterol; SD - standard deviation; TC - total cholesterol; TG - triglyceride.</p><p>*Only median is reported for TG, as the trait's distribution is not Gaussian.</p

Nominally significant SNPs from the longitudinal models in the GLACIER Study (N = 3,495 for ΔTC; N = 2,211 for ΔTG).

<p>95% CI–95% confidence interval; β - beta coefficient; ΔTC - total cholesterol change; ΔTG - triglyceride change; EA - effect allele; EAF - effect allele frequency; FDR - false discovery rate; SE - standard error; SNP - single nucleotide polymorphism</p><p><i>P</i> values are based on linear regression models. SNP associations were tested by fitting the previously associated individual variants (additive model) as the independent variables with lipid trait changes as dependent variables. We adjusted the raw <i>P</i> values for multiple-testing using Benjamini-Hochberg's FDR.</p

TC and TG level changes (95% CI) over 10-yr follow-up by wGRS quartiles.

<p>The TC wGRS was robustly associated with TC changes over follow-up (β = 0.02 mmol/l per allele per follow-up, 95% CI =  0.01, 0.03, SE = 0.003, <i>P</i> = 9.8*10⁻¹⁸) (<b>A</b>). The TG wGRS was robustly associated with TG changes over follow-up (β = 0.03 mmol/l per allele per follow-up, 95% CI =  0.02, 0.04, SE = 0.005, <i>P</i> = 6.5*10⁻¹¹) (<b>B</b>).</p

Replication of lipid associations in MDC (N = 2,943).

<p>95% CI–95% confidence interval; β - beta coefficient; ΔHDL-C - high density lipoprotein cholesterol change; ΔLDL-C - low density lipoprotein cholesterol change; ΔTC - total cholesterol change; ΔTG - triglyceride change; EA - effect allele; EAF - effect allele frequency; SE - standard error; SNP - single nucleotide polymorphism</p><p><i>P</i> values for lipid changes are based on linear regression models, marginal effects were tested by fitting the previously statistically nominally significantly associated single variants (additive model) as the independent variables with lipid trait changes as dependent variables.</p

Pairwise differences between ROC AUC curves and classification statistics in relation to hyperlipidemia in GLACIER (N = 1,257 for TC; N = 1,660 for TG).

<p>NPV - negative predictive value; PPV - positive predictive value; ROC AUC - receiver operating characteristics area under the curve; TC - total cholesterol; TG - triglyceride.</p><p><i>P</i> values are calculated by a chi squared test comparing two ROC AUC curves.</p><p>Model 1  =  age,age²;sex,BMI; Model 2 =  Model 1+ trait specific GRS; Model 3 =  Model 1+ traditional risk factors (cholesterol intake, trans fat intake, saturated fat intake, carbohydrate intake, alcohol intake, physical activity); Model 4 =  Model 1+ trait specific GRS + traditional risk factors.</p

Longitudinal characteristics of the GLACIER Study participants (N = 3,495 for TC; N = 2,211 for TG).

<p>BMI - body mass index; IQR - interquartile range; SD - standard deviation; TC - total cholesterol; TG - triglyceride.</p><p>*Only median is reported for TG, as the trait's distribution is not Gaussian.</p

Baseline characteristics of the GLACIER Study participants (N = 5,862).

<p>BMI - body mass index; HDL-C - high density lipoprotein cholesterol; IQR - interquartile range; LDL-C - low density lipoprotein cholesterol; SD - standard deviation; TC - total cholesterol; TG - triglyceride.</p><p>*Only median is reported for TG, as the trait's distribution is not Gaussian.</p

The pedigree included in the current study.

<p>Affected individuals are indicated in black, unaffected in white. An obligate carrier of the chromosome 1 putative scoliosis risk haplotype (denoted by blue bars) is marked with a black dot. All numbered individuals have been genotyped and included in the linkage analysis. All putative non-risk haplotypes are denoted by white bars. The two exome-sequenced individuals are marked with asterisks. Carriers of the rare <i>CELSR2</i> variant identified by exome sequencing are marked by a green box.</p

Schematic of the structure of the <i>CELSR2</i> protein.

<p>Shown are the cadherin, EGF-like, and laminin-G-like domains. Also the transmembrane (TM) 7-pass domain and the evolutionarily conserved GAIN domain. The GAIN domain contains within it a GPS domain and is the site of autoproteolytic cleavage of <i>CELSR2</i>. The rare V2287I variant and more common R2060R tagging variant are both located within the GAIN domain.</p

Genetic linkage peak on chromosome 1, indicating sharing in all affected individuals.

<p>The maximum K&C non-parametric LOD (NPL) score was attained through the exponential model. The x-axis shows the position on the chromosome (in cM), the y-axis shows the NPL score.</p