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Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevención con Dieta Mediterránea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDAS-derived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altman's analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P < 0.001) to HDL-cholesterol (HDL-C) and inversely (P < 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P < 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.