BackgroundTools for the prediction of atrial fibrillation (AF) may identify high‐risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors.Methods and ResultsIndividual‐level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment—Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5‐year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C‐statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C‐statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, −0.0032; 95% CI, −0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C‐statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C‐statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate.ConclusionA risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.

Background C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We aimed to identify genetic variants that are associated with CRP levels. Methods and Results We performed a genome wide association (GWA) analysis of CRP in 66,185 participants from 15 population-based studies. We sought replication for the genome wide significant and suggestive loci in a replication panel comprising 16,540 individuals from ten independent studies. We found 18 genome-wide significant loci and we provided evidence of replication for eight of them. Our results confirm seven previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2), immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1), or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found significant interaction of body mass index (BMI) with LEPR (p<2.9×10−6). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained approximately 5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. Conclusion We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.

HERITABLE COMPONENT UNderlying atrial fibrillation (AF) has been well demonstrated, [1][2][3][4][5][6] and it is now evident that genetic variants are associated with AF risk. [7][8][9][10] However, the role of familial occurrence across and within generations has received little attention.Several gaps in knowledge exist regarding the association between familial AF and AF risk. Although AF risk appears greater with younger age of AF onset in relatives, 1,2 the magnitude of risk attributable to familial AF has not been characterized across a wide range of AF onset ages in family members. Whereas occurrence of AF in a firstdegree relative is associated with newonset AF, only parental AF has been demonstrated to confer risk independent of other AF risk factors. 1 The association between sibling AF and AF risk after accounting for parental disease has not been examined. Importantly, the extent to which risk conferred by familial AF is mediated by

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