Multivariate and Gene-Based Association Testing of Sarcopenia: Bushehr Elderly Health Program (BEH)

Mohammad Noorchenarboo; Mahdi Akbarzadeh; Noushin Fahimfar; Gita Shafiee; Hamed Moheimani; Kazem Khalagi; Mahsa Mohammad Amoli; Bagher Larijani; Iraj Nabipour; Afshin Ostovar; Abbas Dehghan; Mehdi Yaseri

doi:10.18502/jbe.v8i2.10417

Mohammad Noorchenarboo Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Akbarzadeh Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Noushin Fahimfar Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Gita Shafiee Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Hamed Moheimani Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Kazem Khalagi Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mahsa Mohammad Amoli Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Bagher Larijani Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Iraj Nabipour The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
Afshin Ostovar Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abbas Dehghan The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.
Mehdi Yaseri Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

DOI: https://doi.org/10.18502/jbe.v8i2.10417

Keywords: Bushehr Elderly Health Program (BEH); MultiPhen; GATES; IL10; Candidate-gene; GWAS

Abstract

Introduction: There is a strong correlation between the skeletal muscle mass index (SMI) and handgrip strength as indicators of sarcopenias. Multivariate methods can be exploited statistical power in determining the association between these correlated heritable indicators.

Methods: We conducted a multivariate candidate-gene study based on data collected from the ongoing Bushehr Elderly Health (BEH) cohort, which evaluated the prevalence of musculoskeletal disorders in 2772 Iranians over 60 years old with 663377 single nucleotide polymorphisms (SNPs). We chose genetic variants on IL10 (chromosome 1: 206940947, 206945839), a strongly associated gene known to cause muscle diseases, as candidate regions, which included 27 independent SNPs with LD<0.4 (MAF>0.01 and p-valuehwe >0.05). MultiPhen uses a linear combination of genotypes, including SMI and handgrip, to obtain stronger statistical power. To outperform and confirm the MultiPhen results, it combined with a summary statistics level genebased association test, GATES.

Results: Among the participants, 1138 men (48%) and 1205 women (52%) aged 69.2±6.35 and 69.56±6.45, were present respectively. 27 SNPs with a maximum MAF of 0.488 and a minimum of 0.0098, p-value hwe=0.3 were selected on Interleukin 10 (IL10). In the joint model MultiPhen test, 3 intronic variants (rs11119603, rs3950619, rs57461190) were associated with IL10 with effect sizes between 0.178 and 0.883 (p-value<0.05). We used the GATES model to assess the multivariate aggregated effect of IL10 on the phenotypes. Using this method, the gene's effect was significant (0.046), showing that it is a risk gene for sarcopenia.

Conclusion: This study examined the association of handgrip, SMI, with IL10, as demonstrated in previous studies as risk factors for muscular diseases, using multivariate methods that utilized a joint model to achieve a high level of statistical power.