Dataset Information

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

ABSTRACT: It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects???65 years of age than among those?>?65 years (interaction p-value?=?4.0?×?10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value?=?1.7?×?10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

SUBMITTER: Weng LC

PROVIDER: S-EPMC5595875 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

Weng Lu-Chen LC Lunetta Kathryn L KL Müller-Nurasyid Martina M Smith Albert Vernon AV Thériault Sébastien S Weeke Peter E PE Barnard John J Bis Joshua C JC Lyytikäinen Leo-Pekka LP Kleber Marcus E ME Martinsson Andreas A Lin Henry J HJ Rienstra Michiel M Trompet Stella S Krijthe Bouwe P BP Dörr Marcus M Klarin Derek D Chasman Daniel I DI Sinner Moritz F MF Waldenberger Melanie M Launer Lenore J LJ Harris Tamara B TB Soliman Elsayed Z EZ Alonso Alvaro A Paré Guillaume G Teixeira Pedro L PL Denny Joshua C JC Shoemaker M Benjamin MB Van Wagoner David R DR Smith Jonathan D JD Psaty Bruce M BM Sotoodehnia Nona N Taylor Kent D KD Kähönen Mika M Nikus Kjell K Delgado Graciela E GE Melander Olle O Engström Gunnar G Yao Jie J Guo Xiuqing X Christophersen Ingrid E IE Ellinor Patrick T PT Geelhoed Bastiaan B Verweij Niek N Macfarlane Peter P Ford Ian I Heeringa Jan J Franco Oscar H OH Uitterlinden André G AG Völker Uwe U Teumer Alexander A Rose Lynda M LM Kääb Stefan S Gudnason Vilmundur V Arking Dan E DE Conen David D Roden Dan M DM Chung Mina K MK Heckbert Susan R SR Benjamin Emelia J EJ Lehtimäki Terho T März Winfried W Smith J Gustav JG Rotter Jerome I JI van der Harst Pim P Jukema J Wouter JW Stricker Bruno H BH Felix Stephan B SB Albert Christine M CM Lubitz Steven A SA

Scientific reports 20170912 1

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent st ...[more]

PMID: 28900195

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Project description:RationaleObesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity.MethodsWe used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate.ResultsThis cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m2. The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of -0.03 mmol/L in bicarbonate for each 1 kg/m2 increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status.ConclusionContrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.

Dataset Information

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

Publications

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

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