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A genetically informed investigation into the relationship between childhood maltreatment and adult health

بررسی مبتنی بر ژنتیک در رابطه بین بدرفتاری دوران کودکی و سلامت بزرگسالی

Solveig Løkhammer, Eleni Friligkou, Dóra Koller, Jun He, Brenda Cabrera‐Mendoza, Stéphanie Le Hellard, Renato A Polimanti

Translational Psychiatry 2026
https://doi.org/10.1038/s41398-026-04498-1

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چکیده

The underlying mechanisms linking childhood maltreatment (CM) to adverse health outcomes are unclear. Here, we estimated CM pleiotropy across human phenome, also assessing the role of socioeconomic factors. Specifically, we performed a phenome-wide association study (PheWAS) of CM-associated loci using electronic health records and genetic data from the All of Us Research Program (N = 98,551), FinnGen Project (N = 377,277), and Million Veteran Program (N = 449,042). To characterize CM pleiotropy, we also conducted genetic correlation (rg), latent causal variable analysis (LCV), and bidirectional Mendelian randomization (MR) analyses. Additionally, multi-trait conditional and joint analysis and multivariate MR (MVMR) were performed to estimate whether genetically inferred CM associations are partially explained by household income (HI, a proxy for socioeconomic factors). PheWAS revealed CM loci associations with 66 medical outcomes (p < 2.76 × 10 −6 ), including psychiatric, musculoskeletal, circulatory, neurologic, and respiratory conditions. Similarly, we observed 285 CM genetic correlations (p < 3.24 × 10 −5 ) with a range of medical domains. Among them, emotional disorders starting during childhood or adolescence showed the highest CM genetic overlap (rg=0.75). LCV analysis revealed CM genetic relationships with musculoskeletal, metabolic, respiratory, and eye-related outcomes. For these, MR analyses highlighted bidirectional and heterogeneous effects possibly due to dynastic confounders, and MVMR showed a reduced effect of CM genetic liability after accounting for HI. In conclusion, different pleiotropic mechanisms likely contribute to CM relationships with several health domains, which appear to be at least partially explained by socioeconomic factors.

چکیده به فارسی

سازوکارهای زیربنایی که بدرفتاری دوران کودکی (CM) را به پیامدهای نامطلوب سلامت مرتبط می‌کنند، هنوز به‌روشنی مشخص نشده‌اند. در این پژوهش، پلیوتروپی CM در سراسر فنوم انسانی برآورد شد و همچنین نقش عوامل اجتماعی‌اقتصادی مورد ارزیابی قرار گرفت. به طور مشخص، مطالعه انجمنی فنوم‌گسترده (PheWAS) بر روی جایگاه‌های مرتبط با CM با استفاده از پرونده‌های الکترونیک سلامت و داده‌های ژنتیکی از برنامه پژوهشی All of Us (N = 98,551)، پروژه FinnGen (N = 377,277) و برنامه Million Veteran (N = 449,042) انجام شد. برای توصیف پلیوتروپی CM، همبستگی ژنتیکی (rg)، تحلیل متغیر علّی نهفته (LCV) و تحلیل‌های تصادفی‌سازی مندلی دوطرفه (MR) نیز صورت گرفت. افزون بر این، تحلیل شرطی و مشترک چندصفتی و تصادفی‌سازی مندلی چندمتغیره (MVMR) برای برآورد این‌که آیا ارتباطات استنباط‌شده ژنتیکی CM تا حدی توسط درآمد خانوار (HI، به عنوان نماینده‌ای برای عوامل اجتماعی‌اقتصادی) تبیین می‌شود، انجام شد. PheWAS ارتباط جایگاه‌های CM را با ۶۶ پیامد پزشکی (p < 2.76 × 10 −6) از جمله اختلالات روان‌پزشکی، اسکلتی‌عضلانی، گردش خون، عصبی و تنفسی نشان داد. به طور مشابه، ۲۸۵ همبستگی ژنتیکی CM (p < 3.24 × 10 −5) با دامنه‌ای از حوزه‌های پزشکی مشاهده شد. در میان آن‌ها، اختلالات هیجانی آغازشونده در دوران کودکی یا نوجوانی بیشترین همپوشانی ژنتیکی با CM را نشان دادند (rg=0.75). تحلیل LCV روابط ژنتیکی CM با پیامدهای اسکلتی‌عضلانی، متابولیک، تنفسی و مرتبط با چشم را آشکار ساخت. برای این موارد، تحلیل‌های MR اثرات دوطرفه و ناهمگن را که احتمالاً ناشی از عوامل مخدوش‌کننده سلسله‌ای هستند، برجسته کرد و MVMR کاهش اثر استعداد ژنتیکی CM پس از لحاظ درآمد خانوار را نشان داد. در نتیجه، به نظر می‌رسد سازوکارهای پلیوتروپیک متفاوتی در روابط CM با چندین حوزه سلامت نقش دارند که این روابط دست‌کم تا حدی توسط عوامل اجتماعی‌اقتصادی تبیین می‌شوند.

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موضوع‌ها و کلیدواژه‌ها

تنفسروان‌پزشکینوجوانیAdverse Childhood Experienceschild abuseadult healthgene-environment interactiongenetic epidemiologyhealth outcomes

ارجاع

Løkhammer, S., Friligkou, E., Koller, D., He, J., Cabrera‐Mendoza, B., Hellard, S. L., & Polimanti, R. A. (2026). A genetically informed investigation into the relationship between childhood maltreatment and adult health. Translational Psychiatry. https://doi.org/10.1038/s41398-026-04498-1

(Løkhammer et al., 2026)

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  1. با احترام و بدون توهین، تحقیر، برچسب‌زنی یا حمله‌ی شخصی با دیگران گفتگو کنید.
  2. از نوشتن هرگونه اطلاعات هویتی یا قابل‌شناسایی مراجعان، بیماران یا اشخاص ثالث، از جمله نام، شماره‌ی تماس، تصویر، نشانی، محل کار یا جزئیات منحصربه‌فرد پرونده خودداری کنید.
  3. اگر درباره‌ی یک تجربه‌ی بالینی سؤال می‌کنید، اطلاعات را تا حد ممکن بی‌نام و کلی بیان کنید تا امکان شناسایی فرد وجود نداشته باشد.
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  6. انتشار تبلیغات، معرفی خدمات شخصی، شماره‌ی تلفن، شناسه‌ی شبکه‌های اجتماعی، پیوند تبلیغاتی یا درخواست جذب مراجع در این بخش مجاز نیست.
  7. در بیان ادعاهای علمی، به‌ویژه درباره‌ی اثربخشی درمان‌ها، تشخیص یا یافته‌های پژوهشی، تا حد امکان نام منبع معتبر، مقاله یا راهنمای علمی را ذکر کنید.
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چکیده

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