%0 Journal Article %J Br J Nutr %D 2018 %T Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function. %A Xu, Jiayi %A Bartz, Traci M %A Chittoor, Geetha %A Eiriksdottir, Gudny %A Manichaikul, Ani W %A Sun, Fangui %A Terzikhan, Natalie %A Zhou, Xia %A Booth, Sarah L %A Brusselle, Guy G %A de Boer, Ian H %A Fornage, Myriam %A Frazier-Wood, Alexis C %A Graff, Mariaelisa %A Gudnason, Vilmundur %A Harris, Tamara B %A Hofman, Albert %A Hou, Ruixue %A Houston, Denise K %A Jacobs, David R %A Kritchevsky, Stephen B %A Latourelle, Jeanne %A Lemaitre, Rozenn N %A Lutsey, Pamela L %A O'Connor, George %A Oelsner, Elizabeth C %A Pankow, James S %A Psaty, Bruce M %A Rohde, Rebecca R %A Rich, Stephen S %A Rotter, Jerome I %A Smith, Lewis J %A Stricker, Bruno H %A Voruganti, V Saroja %A Wang, Thomas J %A Zillikens, M Carola %A Barr, R Graham %A Dupuis, Josée %A Gharib, Sina A %A Lahousse, Lies %A London, Stephanie J %A North, Kari E %A Smith, Albert V %A Steffen, Lyn M %A Hancock, Dana B %A Cassano, Patricia A %X

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

%B Br J Nutr %P 1-12 %8 2018 Sep 12 %G eng %R 10.1017/S0007114518002180 %0 Journal Article %J Am J Respir Crit Care Med %D 2018 %T Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-Pulmonary Function Association. %A Xu, Jiayi %A Gaddis, Nathan C %A Bartz, Traci M %A Hou, Ruixue %A Manichaikul, Ani W %A Pankratz, Nathan %A Smith, Albert V %A Sun, Fangui %A Terzikhan, Natalie %A Markunas, Christina A %A Patchen, Bonnie K %A Schu, Matthew %A Beydoun, May A %A Brusselle, Guy G %A Eiriksdottir, Gudny %A Zhou, Xia %A Wood, Alexis C %A Graff, Mariaelisa %A Harris, Tamara B %A Ikram, M Arfan %A Jacobs, David R %A Launer, Lenore J %A Lemaitre, Rozenn N %A O'Connor, George %A Oelsner, Elizabeth C %A Psaty, Bruce M %A Ramachandran, Vasan S %A Rohde, Rebecca R %A Rich, Stephen S %A Rotter, Jerome I %A Seshadri, Sudha %A Smith, Lewis J %A Tiemeier, Henning %A Tsai, Michael Y %A Uitterlinden, André G %A Voruganti, V Saroja %A Xu, Hanfei %A Zilhão, Nuno R %A Fornage, Myriam %A Zillikens, M Carola %A London, Stephanie J %A Barr, R Graham %A Dupuis, Josée %A Gharib, Sina A %A Gudnason, Vilmundur %A Lahousse, Lies %A North, Kari E %A Steffen, Lyn M %A Cassano, Patricia A %A Hancock, Dana B %X

RATIONALE: Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.

OBJECTIVE: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.

METHODS: Associations of n-3 PUFA biomarkers (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (forced expiratory volume in the first second [FEV], forced vital capacity [FVC], and [FEV/FVC]) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of single nucleotide polymorphism (SNP) associations and their interactions with n-3 PUFAs.

RESULTS: DPA and DHA were positively associated with FEV1 and FVC (P<0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P=9.4×10 across discovery and replication cohorts). The rs11693320-A allele (frequency~80%) was associated with lower FVC (P=2.1×10; β= -161.0mL), and the association was attenuated by higher DHA levels (P=2.1×10; β=36.2mL).

CONCLUSIONS: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.

%B Am J Respir Crit Care Med %8 2018 Sep 10 %G eng %R 10.1164/rccm.201802-0304OC