Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

Tsepilov, Yakov A.; Freidin, Maxim B.; Shadrina, Alexandra S.; Sharapov, Sodbo; Elgaeva, Elizaveta E.; Zundert, Jan Van; Karssen, Lennart C.; Suri, Pradeep; Williams, Frances; Aulchenko, Yurii S.

doi:10.1038/s42003-020-1051-9

Cited by 54 publications

(91 citation statements)

References 97 publications

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“…To estimate the effect of each SNP on each of the latent variables or factors, we first used GemonicSEM to estimate the loadings of each observed variable onto the latent one. We then applied the method described in Tsepilov et al 2020 33 . Briefly the effect of each SNP on each factor is estimated as the weighted linear combination of the effect of the SNP on each index variable, where the weights are represented by the loadings of each item on the latent variable.…”

Section: Estimation Of the Effect Of Each Snp With Each Factormentioning

confidence: 99%

Large-scale genome-wide association study of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits

May-Wilson

Matoba

Wade

et al. 2021

Preprint

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Variable preferences for different foods are among the main determinants of their intake and are influenced by many factors, including genetics. Despite considerable twins' heritability, studies aimed at uncovering food-liking genetics have focused mostly on taste receptors. Here, we present the first results of a large-scale genome-wide association study of food liking conducted on 161,625 participants from UK Biobank. Liking was assessed over 139 specific foods using a 9-point hedonic scale. After performing GWAS, we used genetic correlations coupled with structural equation modelling to create a multi-level hierarchical map of food liking. We identified three main dimensions: high caloric foods defined as "Highly palatable", strong-tasting foods ranging from alcohol to pungent vegetables, defined as "Learned" and finally "Low caloric" foods such as fruit and vegetables. The "Highly palatable" dimension was genetically uncorrelated from the other two, suggesting that two independent processes underlie liking high reward foods and the Learned/Low caloric ones. Genetic correlation analysis with the corresponding food consumption traits revealed a high correlation, while liking showed twice the heritability compared to consumption. For example, fresh fruit liking and consumption showed a genetic correlation of 0.7 with heritabilities of 0.1 and 0.05, respectively. GWAS analysis identified 1401 significant food-liking associations located in 173 genomic loci, with only 11 near taste or olfactory receptors. Genetic correlation with morphological and functional brain data (33,224 UKB participants) uncovers associations of the three food-liking dimensions with non-overlapping, distinct brain areas and networks, suggestive of separate neural mechanisms underlying the liking dimensions. In conclusion, we created a comprehensive and data-driven map of the genetic determinants and associated neurophysiological factors of food liking beyond taste receptor genes.

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Section: Estimation Of the Effect Of Each Snp With Each Factormentioning

confidence: 99%

Large-scale genome-wide association study of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits

May-Wilson

Matoba

Wade

et al. 2021

Preprint

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“…В исследовании, проведенном в 2020 г. [41], выявлена связь 5 генов (SLC398A, ECM1, EXD3, FOXP2 и AMIGO3), ассоциированных с хронической болью. Авторы полагают, что скелетно-мышечная боль при ОА определяется многими признаками, связанными с нервной системой и генетическими корреляциями с антропологическими, социально-демографическими, психиатрическими компонентами.…”

Section: заключениеunclassified

Association of the rs2167270 polymorphism of the leptin gene (LEP) with the intensity of pain in patients with osteoarthritis of the knee

Крылов¹,

Алексеева²,

Шарапова³

2021

Obes. metabol.

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Background: Osteoarthritis (OA) is a significant social problem as it is the most common disease of the joints. OA is a multifactorial disease in which great attention is paid to hereditary factors. Recently, a number of studies have demonstrated the contribution of a number of genes to the subjective assessment of pain in OA, which is the main symptom of this disease. The association of P2X7, TRPV1 and TACR1 genes and some others with pain sensitivity has been shown. One of the risk factors of pain among many others, is the increased weight. Abdominal adipose tissue is a source of release of pro-inflammatory adipokines that cause systemic inflammation associated with damage to many tissues, including subchondral bone, synovial membrane. Leptin is an endogenous hormone from the adipokine family encoded by the obesity gene leptin (LEP) and which is synthesized primarily in adipocytes.Aims: To investigate the possible association of rs2167270 (A19G) polymorphism of the LEP gene with pain intensity in patients with knee OA.Materials and methods: The study was conducted among women diagnosed with OA. Using the VAS scale (Visual analog scale), patients with mild knee pain — group 1 (VAS ≤ 40 mm) and patients with moderate or severe pain — group 2 (VAS>40 mm) were selected for pain assessment. Genetic variants of A19G leptin gene polymorphism were studied by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP) method.Results: In the group of patients with moderate or severe pain intensity (group 2, n=61), a statistically significant association was shown with a higher body mass index (p=0.006) and an increased frequency of carriers of the 19GG genotype (p=0,051) compared to group 1 (n=36). Carriers of the 19GG genotype statistically significantly had a higher rate of knee pain and an early age of OA debut compared to carriers of the 19AA genotype (p=0,035 and p=0,015, respectively).Conclusions: The findings open up new possibilities for predicting pain symptoms in patients with knee OA by genetic testing of A19G polymorphic variants of the leptin gene.

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“…We used LD-score regression to assess test score inflation, SNP-based heritability, and to assess genetic correlations among PA-liking traits and previously reported PA traits 22 . To obtain a measure of overall PA liking, we also derived a GWAS of the first principal component (PC) derived through the genetically-independent phenotype (GIP) method 23,24 and starting from the genetic correlation matrix to derive the loadings of each trait on each GIP. Independent significant loci were identified as those with p < 5 × 10 -8 with r 2 < 0.1, and > 250 kb distance.…”

Section: Statistical Analysesmentioning

confidence: 99%

Genome-wide association study of liking of physical activity in the UK Biobank

Klimentidis

Newell

Zee

et al. 2021

Preprint

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A lack of physical activity (PA) is one of the most pressing health issues facing society today. Our individual propensity for PA is partly influenced by genetic factors. Stated liking of various PA behaviors may capture additional dimensions of PA behavior that are not captured by other measures, and contribute to our understanding of the genetics of PA behavior. Here, in over 157,000 individuals from the UK Biobank, we sought to complement and extend previous findings on the genetics of PA behavior by performing genome-wide association studies of self-reported liking of several PA-related behaviors plus an additional derived trait of overall PA-liking. We identified a total of 19 unique genome-wide significant loci across all traits, only four of which overlap with loci previously identified for PA behavior. The PA-liking traits were genetically correlated with self-reported (rg: 0.38 to 0.80) and accelerometry-derived (rg: 0.26 to 0.49) PA measures, and with a wide range of health-related traits and dietary behaviors. Replication in the Netherlands Twin Register (NTR; n>7,300) and the TwinsUK (n>1,300) study revealed directionally consistent associations. Polygenic risk scores (PRS) were then trained in UKB for each PA-liking trait and for self-reported PA behavior. The PA-liking PRS significantly predicted the same liking trait in NTR. The PRS for liking of going to the gym predicted PA behavior in NTR (r2 = 0.40%) nearly as well as the one constructed based on self-reported PA behavior (r2 = 0.42%). Combining the two PRS into a single model increased the r2 to 0.59%, suggesting that although these PRS correlate with each other, they are also capturing distinct dimensions of PA behavior. In conclusion, we have identified the first loci associated with PA-liking, and extended and refined our understanding of the genetic basis of PA behavior.

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Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

Cited by 54 publications

References 97 publications

Large-scale genome-wide association study of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits

Large-scale genome-wide association study of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits

Association of the rs2167270 polymorphism of the leptin gene (LEP) with the intensity of pain in patients with osteoarthritis of the knee

Genome-wide association study of liking of physical activity in the UK Biobank

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