@article {8527,
	title = {{Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels},
	journal = {Circulation},
	volume = {139},
	year = {2019},
	month = {01},
	pages = {620{\textendash}635},
	abstract = {Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF.\ We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated {\^a}{\textperthousand}{\textasciicircum}35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events.\ We identified 13 novel genome-wide significant ( P{\^a}{\textperthousand}¤2.5{\~A}{\textemdash}10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk.\ The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.},
	author = {Sabater-Lleal, M. and Huffman, J. E. and de Vries, P. S. and Marten, J. and Mastrangelo, M. A. and Song, C. and Pankratz, N. and Ward-Caviness, C. K. and Yanek, L. R. and Trompet, S. and Delgado, G. E. and Guo, X. and Bartz, T. M. and Martinez-Perez, A. and Germain, M. and de Haan, H. G. and Ozel, A. B. and Polasek, O. and Smith, A. V. and Eicher, J. D. and Reiner, A. P. and Tang, W. and Davies, N. M. and Stott, D. J. and Rotter, J. I. and Tofler, G. H. and Boerwinkle, E. and de Maat, M. P. M. and Kleber, M. E. and Welsh, P. and Brody, J. A. and Chen, M. H. and Vaidya, D. and Soria, J. M. and Suchon, P. and van Hylckama Vlieg, A. and Desch, K. C. and Kolcic, I. and Joshi, P. K. and Launer, L. J. and Harris, T. B. and Campbell, H. and Rudan, I. and Becker, D. M. and Li, J. Z. and Rivadeneira, F. and Uitterlinden, A. G. and Hofman, A. and Franco, O. H. and Cushman, M. and Psaty, B. M. and Morange, P. E. and McKnight, B. and Chong, M. R. and Fernandez-Cadenas, I. and Rosand, J. and Lindgren, A. and Gudnason, V. and Wilson, J. F. and Hayward, C. and Ginsburg, D. and Fornage, M. and Rosendaal, F. R. and Souto, J. C. and Becker, L. C. and Jenny, N. S. and M?rz, W. and Jukema, J. W. and Dehghan, A. and Tr?gou?t, D. A. and Morrison, A. C. and Johnson, A. D. and O{\textquoteright}Donnell, C. J. and Strachan, D. P. and Lowenstein, C. J. and Smith, N. L.}
}
@article {8532,
	title = {{Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association},
	journal = {Am J Respir Crit Care Med},
	volume = {199},
	year = {2019},
	month = {03},
	pages = {631{\textendash}642},
	abstract = {Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.\ To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.\ Associations of n-3 PUFA biomarkers ({\^I}{\textpm}-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/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 SNP associations and their interactions with n-3 PUFAs.\ 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 (P2df = 9.4 {\~A}{\textemdash} 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, {\^a}{\textasciicircum}{\textonequarter}80\%) was associated with lower FVC (PSNP = 2.1 {\~A}{\textemdash} 10-9; {\^I}{\texttwosuperior}SNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP{\~A}{\textemdash}DHA interaction = 2.1 {\~A}{\textemdash} 10-7; {\^I}{\texttwosuperior}SNP{\~A}{\textemdash}DHA interaction = 36.2 ml).\ 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.},
	author = {Xu, J. and Gaddis, N. C. and Bartz, T. M. and Hou, R. and Manichaikul, A. W. and Pankratz, N. and Smith, A. V. and Sun, F. and Terzikhan, N. and Markunas, C. A. and Patchen, B. K. and Schu, M. and Beydoun, M. A. and Brusselle, G. G. and Eiriksdottir, G. and Zhou, X. and Wood, A. C. and Graff, M. and Harris, T. B. and Ikram, M. A. and Jacobs, D. R. and Launer, L. J. and Lemaitre, R. N. and O{\textquoteright}Connor, G. T. and Oelsner, E. C. and Psaty, B. M. and Vasan, R. S. and Rohde, R. R. and Rich, S. S. and Rotter, J. I. and Seshadri, S. and Smith, L. J. and Tiemeier, H. and Tsai, M. Y. and Uitterlinden, A. G. and Voruganti, V. S. and Xu, H. and Zilh?o, N. R. and Fornage, M. and Zillikens, M. C. and London, S. J. and Barr, R. G. and Dupuis, J. and Gharib, S. A. and Gudnason, V. and Lahousse, L. and North, K. E. and Steffen, L. M. and Cassano, P. A. and Hancock, D. B.}
}
@article {8494,
	title = {{Mitochondrial DNA copy number and incident atrial fibrillation},
	journal = {BMC Med},
	volume = {18},
	year = {2020},
	month = {Sep},
	pages = {246},
	abstract = {Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown.\ We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates.\ The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13\% increased risk (95\% CI 1 to 27\%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups.\ Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.},
	author = {Zhao, D. and Bartz, T. M. and Sotoodehnia, N. and Post, W. S. and Heckbert, S. R. and Alonso, A. and Longchamps, R. J. and Castellani, C. A. and Hong, Y. S. and Rotter, J. I. and Lin, H. J. and O{\textquoteright}Rourke, B. and Pankratz, N. and Lane, J. A. and Yang, S. Y. and Guallar, E. and Arking, D. E.}
}
@article {8999,
	title = {{Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation},
	journal = {Hum Genet},
	volume = {141},
	year = {2022},
	month = {Jan},
	pages = {127{\textendash}146},
	abstract = {).},
	author = {Longchamps, R. J. and Yang, S. Y. and Castellani, C. A. and Shi, W. and Lane, J. and Grove, M. L. and Bartz, T. M. and Sarnowski, C. and Liu, C. and Burrows, K. and Guyatt, A. L. and Gaunt, T. R. and Kacprowski, T. and Yang, J. and De Jager, P. L. and Yu, L. and Bergman, A. and Xia, R. and Fornage, M. and Feitosa, M. F. and Wojczynski, M. K. and Kraja, A. T. and Province, M. A. and Amin, N. and Rivadeneira, F. and Tiemeier, H. and Uitterlinden, A. G. and Broer, L. and van Meurs, J. B. J. and van Duijn, C. M. and Raffield, L. M. and Lange, L. and Rich, S. S. and Lemaitre, R. N. and Goodarzi, M. O. and Sitlani, C. M. and Mak, A. C. Y. and Bennett, D. A. and Rodriguez, S. and Murabito, J. M. and Lunetta, K. L. and Sotoodehnia, N. and Atzmon, G. and Ye, K. and Barzilai, N. and Brody, J. A. and Psaty, B. M. and Taylor, K. D. and Rotter, J. I. and Boerwinkle, E. and Pankratz, N. and Arking, D. E.}
}
@article {9644,
	title = {{A genetic association study of circulating coagulation Factor VIII and von Willebrand Factor levels},
	journal = {Blood},
	year = {2024},
	month = {Feb},
	abstract = {10-9) at seven new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and one for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multi-phenotype analysis of FVIII and VWF identified another three new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, while silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and one for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.},
	author = {de Vries, P. S. and Reventun, P. and Brown, M. R. and Heath, A. S. and Huffman, J. E. and Le, N. Q. and Bebo, A. and Brody, J. A. and Temprano-Sagrera, G. and Raffield, L. M. and Ozel, A. B. and Thibord, F. and Jain, D. and Lewis, J. P. and Rodriguez, B. A. T. and Pankratz, N. and Taylor, K. D. and Polasek, O. and Chen, M. H. and Yanek, L. R. and Carrasquilla, G. D. and Marioni, R. and Kleber, M. E. and t, D. A. and Yao, J. and Li-Gao, R. and Joshi, P. K. and Trompet, S. and Martinez-Perez, A. and Ghanbari, M. and Howard, T. E. and Reiner, A. P. and Arvanitis, M. and Ryan, K. A. and Bartz, T. M. and Rudan, I. and Faraday, N. and Linneberg, A. and Ekunwe, L. and Davies, G. and Delgado, G. E. and Suchon, P. and Guo, X. and Rosendaal, F. R. and Klaric, L. and Noordam, R. and van Rooij, F. and Curran, J. E. and Wheeler, M. M. and Osburn, W. O. and O{\textquoteright}Connell, J. R. and Boerwinkle, E. and Beswick, A. and Psaty, B. M. and Kolcic, I. and Souto, J. C. and Becker, L. C. and Hansen, T. and Doyle, M. F. and Harris, S. E. and Moissl, A. P. and Deleuze, J. F. and Rich, S. S. and van Hylckama Vlieg, A. and Campbell, H. and Stott, D. J. and Soria, J. M. and de Maat, M. P. M. and Almasy, L. and Brody, L. C. and Auer, P. L. and Mitchell, B. D. and Ben-Shlomo, Y. and Fornage, M. and Hayward, C. and Mathias, R. A. and inen, T. O. and Lange, L. A. and Cox, S. R. and rz, W. and Morange, P. E. and Rotter, J. I. and Mook-Kanamori, D. O. and Wilson, J. F. and van der Harst, P. and Jukema, J. W. and Ikram, M. A. and Blangero, J. and Kooperberg, C. and Desch, K. C. and Johnson, A. D. and Sabater-Lleal, M. and Lowenstein, C. J. and Smith, N. L. and Morrison, A. C.}
}
