Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom
Authors: Iris Kleerekooper, Sharon Chua, Paul J. Foster, S. Anand Trip, Gordon T. Plant, Axel Petzold, Praveen Patel, Naomi  Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Catey Bunce, Roxana Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, Valentina Cipriani, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Alexander  Doney, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John Gallacher, David (Ted) Garway-Heath, Jane  Gibson, Dan Gore, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Pearse Keane, Sir Peng Tee  Khaw, Anthony Khawaja, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Phil Luthert, Tom Macgillivray , Sarah Mackie, Bernadette McGuinness, Gareth McKay, Martin McKibbin, Danny Mitry, Tony Moore, James Morgan, Zaynah Muthy, Eoin O'Sullivan , Chris Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Nikolas Pontikos, Jugnoo Rahi, Alicja Rudnicka, Jay Self, Panagiotis Sergouniotis, Sobha Sivaprasad, David Steel, Irene Stratton , Nicholas Strouthidis, Cathie Sudlow, Zihan Sun, Robyn Tapp, Caroline Thaung , Dhanes Thomas , Emanuele Trucco, Adnan Tufail, Stephen Vernon, Ananth Viswanathan, Veronique Vitart, Katie Williams, Cathy  Williams, Jayne Woodside, Max Yates, Jennifer Yip, Yalin Zheng
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling. <h3>Objective</h3> To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021. <h3>Exposures</h3> Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index. <h3>Main Outcomes and Measures</h3> Multiple sclerosis case status and mGCIPL thickness. <h3>Results</h3> A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted β = −3.09 [95% CI, −5.70 to −0.48] μm;<i>P</i> = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (β = −0.93 [95% CI, −1.07 to −0.79] μm;<i>P</i> &lt; .001), but there was no statistically significant association in individuals with MS (β = −2.27 [95% CI, −4.76 to 0.22] μm;<i>P</i> = .07). Smoking was not associated with mGCIPL thickness in MS. However, smoking was associated with greater mGCIPL thickness in control individuals (β = 0.89 [95% CI, 0.74-1.05 μm];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> These findings suggest that high alcohol intake was associated with retinal features indicative of more severe neurodegeneration, whereas smoking was associated with higher odds of being diagnosed with MS.