vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-91vavilov-4811Research ArticleГЕНЕТИКА ПОВЕДЕНИЯBEHAVIORAL GENETICSИспользование полигенных показателей для оценки предрасположенности к манифестации антисоциального поведенияUsing polygenic scores to assess liability to antisocial behaviorКазанцеваА. В.KazantsevaA. V.

 Уфа 

 Ufa 

Kazantsa@mail.ruЯковлеваД. В.YakovlevaD. V.

 Уфа 

 Ufa 

ДавыдоваЮ. Д.DavydovaYu. D.

 Уфа 

 Ufa 

ХуснутдиноваЭ. К.KhusnutdinovaE. K.

 Уфа 

 Ufa 

Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук; Уфимский университет науки и технологийРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences; Ufa University of Science and TechnologyRussian Federation202509102025296838846Copyright © Казанцева А.В., Яковлева Д.В., Давыдова Ю.Д., Хуснутдинова Э.К., 20252025Казанцева А.В., Яковлева Д.В., Давыдова Ю.Д., Хуснутдинова Э.К.Kazantseva A.V., Yakovleva D.V., Davydova Y.D., Khusnutdinova E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4811

Проведенные к настоящему времени полногеномные анализы ассоциаций (GWAS) антисоциального поведения (АП) в европейских популяциях стали предпосылкой для дальнейших исследований по оценке предрасположенности к развитию схожих фенотипов в независимых выборках. В таких работах используются полигенные показатели, которые представляют собой обобщенный балл, учитывающий число «рисковых» аллелей по каждому включенному генетическому локусу. Поскольку в РФ не было проведено GWAS АП, цель настоящего исследования – проведение репликативного исследования предрасположенности к манифестации крайних форм АП (убийств) в российской когорте с использованием подсчета полигенных показателей. Кроме того, задачей было также выявление наилучшей модели, основанной на включении полигенного показателя и социальных факторов в качестве предикторов. Генотипирование 10 «топовых» SNP, идентифицированных ранее в метаанализе GWAS АП (в генах CADM2, REV3L, FOXP1, FOXP2, BDNF, FURIN, XKR6, TMEM18, SORCS3, ZIC4), проведено с помощью ПЦР в реальном времени у лиц, совершивших убийства (N = 227), и в контрольной группе (N = 254) из Волго-Уральского региона РФ. Множественный регрессионный анализ основывался на включении «взвешенных» и «невзвешенных» полигенных показателей и потенциальных социальных факторов в качестве предикторов. Наилучшая регрессионная модель предрасположенности к манифестации крайних форм АП содержала данные генетического профиля по 10 локусам и социальным факторам (черепно-мозговая травма, тяжелые хронические заболевания в анамнезе, табакокурение) и была наиболее значимой для лиц с семейной отягощенностью психическими расстройствами (p = 2 × 10–13). Введение только полигенного показателя в модель объясняло небольшой процент вариации в предрасположенности к АП (1.1–1.5 %), тогда как добавление социальных предикторов увеличивало процент объясненной вариации (16.2–21.2 %). Полученные результаты указывают на большую значимость социальных факторов по сравнению с кумулятивным эффектом 10 локусов в предикции развития АП в исследуемой выборке. Повышенная вероятность его манифестации связана с наличием коморбидного аддиктивного поведения, черепно-мозговой травмы и семейной отягощенности психопатологиями, что может быть результатом наличия «рискового» генетического профиля.

To date, several genome-wide association studies (GWAS) of antisocial behavior (ASB) have been conducted in Europeans, which promoted research aimed at evaluating liability to ASB-related phenotypes in independent samples. Such studies implemented a polygenic score (PGS) approach, which represents a composite score considering a number of “risky” alleles. Since no GWAS of ASB has been conducted in Russians, the present study aimed to perform a replication study of liability to severe criminal behavior (homicide) in individuals from Russia using PGS. Moreover, we sought to obtain the best model considering PGS and potential social factors as predictors. Genotyping of the “top” ten SNPs previously identified in GWAS meta-analysis of ASB (CADM2, REV3L, FOXP1, FOXP2, BDNF, FURIN, XKR6, TMEM18, SORCS3, and ZIC4 genes) was conducted via real-time PCR in 227 homicide offenders and 254 healthy donors from the Volga-Ural region of Russia. Multiple regression models included “weighted” and “unweighted” PGS and potential social factors as predictors. The best regression model of liability to severe ASB was based on genetic effects of examined SNPs and social predictors, including traumatic brain injury, severe chronic disease, and tobacco smoking, which was more pronounced among subjects with a family history of mental illness (p = 2 × 10–13). PGS alone explained a small proportion of variance in liability to ASB (1.1–1.5 %), while the inclusion of social parameters increased variance explained (16.2–21.2 %). Revealed findings evidence a higher impact of social factors than a composite effect of selected “top” SNPs in predicting liability to ASB in the examined cohort. A higher probability of ASB was linked to comorbid substance abuse, traumatic brain injury, and family history of mental illness, which may also represent a result of a “risky” genetic profile.

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The authors declare that there are no conflicts of interest present.