Journal of Peking University(Health Sciences) >
Interaction between ischemic stroke risk loci identified by genome-wide association studies and sleep habits
Received date: 2022-02-27
Online published: 2022-06-14
Supported by
the National Natural Science Foundation of China(81230066);the National Natural Science Foundation of China(81473043);the National Natural Science Foundation of China(81703291);the National Natural Science Foundation of China(81872695)
Objective: To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci. Methods: A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke. Results: A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033). Conclusion: Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.
Key words： Gene loci; Sleep; Ischemic stroke; Interaction
Ruo-tong YANG , Meng-ying WANG , Chun-nan LI , Huan YU , Xiao-wen WANG , Jun-hui WU , Si-yue WANG , Jia-ting WANG , Da-fang CHEN , Tao WU , Yong-hua HU . Interaction between ischemic stroke risk loci identified by genome-wide association studies and sleep habits[J]. Journal of Peking University(Health Sciences), 2022 , 54(3) : 412 -420 . DOI: 10.19723/j.issn.1671-167X.2022.03.004
| 1 | Li W , Wang D , Cao S , et al. Sleep duration and risk of stroke events and stroke mortality: A systematic review and meta-analysis of prospective cohort studies[J]. Int J Cardiol, 2016, 223, 870- 876. |
| 2 | Titova OE , Micha?lsson K , Larsson SC . Sleep duration and stroke: Prospective cohort study and mendelian randomization analysis[J]. Stroke, 2020, 51 (11): 3279- 3285. |
| 3 | Zhou L , Yu K , Yang L , et al. Sleep duration, midday napping, and sleep quality and incident stroke: The Dongfeng-Tongji cohort[J]. Neurology, 2020, 94 (4): e345- e356. |
| 4 | Song Q , Liu X , Zhou W , et al. Long sleep duration and risk of ischemic stroke and hemorrhagic stroke: the Kailuan prospective study[J]. Sci Rep, 2016, 6, 33664. |
| 5 | Reed DL , Sacco WP . Measuring sleep efficiency: What should the denominator be[J]. J Clin Sleep Med, 2016, 12 (2): 263- 266. |
| 6 | Didikoglu A , Maharani A , Tampubolon G , et al. Longitudinal sleep efficiency in the elderly and its association with health[J]. J Sleep Res, 2020, 29 (3): e12898. |
| 7 | Hirata T , Nakamura T , Kogure M , et al. Reduced sleep efficiency, measured using an objective device, was related to an increased prevalence of home hypertension in Japanese adults[J]. Hypertens Res, 2020, 43 (1): 23- 29. |
| 8 | Yan B , Yang J , Zhao B , et al. Objective sleep efficiency predicts cardiovascular disease in a community population: The sleep heart health study[J]. J Am Heart Assoc, 2021, 10 (7): e016201. |
| 9 | Portaluppi F , Tiseo R , Smolensky MH , et al. Circadian rhythms and cardiovascular health[J]. Sleep Med Rev, 2012, 16 (2): 151- 166. |
| 10 | Shahram N , Reed AB , Dillon OB , et al. Accelerometer-derived sleep onset timing and cardiovascular disease incidence: A UK Biobank cohort study[J]. Eur Heart J Digital Health, 2021, (4): 4. |
| 11 | Korostovtseva L . Ischemic stroke and sleep: The linking genetic factors[J]. Cardiol Ther, 2021, 10 (2): 349- 375. |
| 12 | Fan M , Sun D , Zhou T , et al. Sleep patterns, genetic suscepti-bility, and incident cardiovascular disease: A prospective study of 385 292 UK BioBank participants[J]. Eur Heart J, 2020, 41 (11): 1182- 1189. |
| 13 | 王梦莹, 唐迅, 秦雪英, 等. 北方农村地区居民常见慢性非传染性疾病的家系队列研究进展[J]. 中华流行病学杂志, 2018, 39 (1): 94- 97. |
| 14 | 孙可欣, 刘志科, 曹亚英, 等. 北京某社区2型糖尿病患者血糖控制情况与肱踝脉搏波传导速度的相关性研究[J]. 北京大学学报(医学版), 2015, 47 (3): 431- 436. |
| 15 | Ohayon M , Wickwire EM , Hirshkowitz M , et al. National Sleep Foundation's sleep quality recommendations: first report[J]. Sleep Health, 2017, 3 (1): 6- 19. |
| 16 | Cheng YC , Stanne TM , Giese AK , et al. Genome-wide association analysis of young-onset stroke identifies a locus on chromosome 10q25 near HABP2[J]. Stroke, 2016, 47 (2): 307- 316. |
| 17 | Malik R , Chauhan G , Traylor M , et al. Multiancestry genome-wide association study of 520 000 subjects identifies 32 loci associated with stroke and stroke subtypes[J]. Nat Genet, 2018, 50 (4): 524- 537. |
| 18 | Gretarsdottir S , Thorleifsson G , Manolescu A , et al. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke[J]. Ann Neurol, 2008, 64 (4): 402- 409. |
| 19 | Neurology working group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium , the stroke genetics network (SiGN) , the International Stroke Genetics Consortium (ISGC) . Identification of additional risk loci for stroke and small vessel disease: A meta-analysis of genome-wide association studies[J]. Lancet Neurol, 2016, 15 (7): 695- 707. |
| 20 | Matarín M , Brown WM , Scholz S , et al. A genome-wide genotyping study in patients with ischaemic stroke: Initial analysis and data release[J]. Lancet Neurol, 2007, 6 (5): 414- 420. |
| 21 | Traylor M , Farrall M , Holliday EG , et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): A meta-analysis of genome-wide association studies[J]. Lancet Neurol, 2012, 11 (11): 951- 962. |
| 22 | Dichgans M , Malik R , König IR , et al. Shared genetic susceptibility to ischemic stroke and coronary artery disease: A genome-wide analysis of common variants[J]. Stroke, 2014, 45 (1): 24- 36. |
| 23 | Smith JG , Melander O , Lövkvist H , et al. Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: A large-scale genetic association study[J]. Circ Cardiovasc Genet, 2009, 2 (2): 159- 164. |
| 24 | Traylor M , M?kel? KM , Kilarski LL , et al. A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach[J]. PLoS Genet, 2014, 10 (7): e1004469. |
| 25 | Holliday EG , Maguire JM , Evans TJ , et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke[J]. Nat Genet, 2012, 44 (10): 1147- 1151. |
| 26 | Zhu R , Liu X , He Z , et al. miR-146a and miR-196a2 polymorphisms in patients with ischemic stroke in the northern Chinese Han population[J]. Neurochem Res, 2014, 39 (9): 1709- 1716. |
| 27 | Wan XH , Li SJ , Cheng P , et al. NINJ2 polymorphism is asso-ciated with ischemic stroke in Chinese Han population[J]. J Neurol Sci, 2011, 308 (1/2): 67- 71. |
| 28 | Liu ME , Liao YC , Lin RT , et al. A functional polymorphism of PON1 interferes with microRNA binding to increase the risk of ischemic stroke and carotid atherosclerosis[J]. Atherosclerosis, 2013, 228 (1): 161- 167. |
| 29 | Ding H , Xu Y , Bao X , et al. Confirmation of genomewide association signals in Chinese Han population reveals risk loci for ischemic stroke[J]. Stroke, 2010, 41 (1): 177- 180. |
| 30 | Domingues-Montanari S , Fernández-Cadenas I , Del Río-Espinola A , et al. KCNK17 genetic variants in ischemic stroke[J]. Atherosclerosis, 2010, 208 (1): 203- 209. |
| 31 | Zhu Y , Liu K , Tang X , et al. Association between NINJ2 gene polymorphisms and ischemic stroke: A family-based case-control study[J]. J Thromb Thrombolysis, 2014, 38 (4): 470- 476. |
| 32 | Loci associated with ischaemic stroke and its subtypes (SiGN): A genome-wide association study[J]. Lancet Neurol, 2016, 15(2): 174-184. |
| 33 | Ikram MA , Seshadri S , Bis JC , et al. Genomewide association studies of stroke[J]. N Engl J Med, 2009, 360 (17): 1718- 1728. |
| 34 | Zhang Y , Tong Y , Zhang Y , et al. Two novel susceptibility SNPs for ischemic stroke using exome sequencing in Chinese Han population[J]. Mol Neurobiol, 2014, 49 (2): 852- 862. |
| 35 | Grandner MA , Buxton OM , Jackson N , et al. Extreme sleep durations and increased C-reactive protein: effects of sex and ethnoracial group[J]. Sleep, 2013, 36 (5): 769- 779e. |
| 36 | Ramos AR , Jin Z , Rundek T , et al. Relation between long sleep and left ventricular mass (from a multiethnic elderly cohort)[J]. Am J Cardiol, 2013, 112 (4): 599- 603. |
| 37 | Abe T , Aoki T , Yata S , et al. Sleep duration is significantly associated with carotid artery atherosclerosis incidence in a Japanese population[J]. Atherosclerosis, 2011, 217 (2): 509- 513. |
| 38 | Doyle CY , Ruiz JM , Taylor DJ , et al. Associations between objective sleep and ambulatory blood pressure in a community sample[J]. Psychosom Med, 2019, 81 (6): 545- 556. |
| 39 | Lao XQ , Liu X , Deng HB , et al. Sleep quality, sleep duration, and the risk of coronary heart disease: A prospective cohort study with 60 586 adults[J]. J Clin Sleep Med, 2018, 14 (1): 109- 117. |
| 40 | Massar SAA , Liu JCJ , Mohammad NB , et al. Poor habitual sleep efficiency is associated with increased cardiovascular and cortisol stress reactivity in men[J]. Psychoneuroendocrinology, 2017, 81, 151- 156. |
| 41 | Yang L , Chu Y , Wang L , et al. Overexpression of CRY1 protects against the development of atherosclerosis via the TLR/NF-κB pathway[J]. Int Immunopharmacol, 2015, 28 (1): 525- 530. |
| 42 | Roenneberg T , Kuehnle T , Juda M , et al. Epidemiology of the human circadian clock[J]. Sleep Med Rev, 2007, 11 (6): 429- 438. |
| 43 | Kirchhof P , Kahr PC , Kaese S , et al. PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression[J]. Circ Cardiovasc Genet, 2011, 4 (2): 123- 133. |
| 44 | Li H , Cai Y , Xu AD . Association study of polymorphisms in the ABO gene and their gene-gene interactions with ischemic stroke in Chinese population[J]. J Clin Lab Anal, 2018, 32 (4): e22329. |
| 45 | Sandford AJ , Ha A , Ngan DA , et al. Adhesion molecule gene variants and plasma protein levels in patients with suspected obstructive sleep apnea[J]. PLoS One, 2019, 14 (1): e0210732. |
/
| 〈 |
|
〉 |