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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Developed by Indonesia ITTC
Published on 3/22/2023
Abstract
Abstrak
Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci from published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent single-nucleotide polymorphisms were genome-wide significant (P < 5 × 10–8) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis and 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets.
Kecenderungan genetic terhadap gangguan penyalahgunaan NAPZA dapat diuraikan ke dalam lokus yang membuat risiko adiksi secara umum maupun spesifik terhadap zat tertentu. Kami melaporkan hasil meta-analisa asosiasi multivariat genom yang memisahkan lokus adiksi secara umum dan lokus yang spesifik terhadap zat tertentudari statistik ringkasan yang dipublikasikan terkait dengan penggunaan alkohol bermasalah, tembakau, gangguan penggunaan ganja dan opiat pada sampel dengan jumlah 1.025.550 orang keturunan Eropa dan 92.630 orang keturunan Afrika. Sebanyak 19 polimorfisme nukleotida tunggal independen signifikan untuk seluruh genom (P < 5 × 10–8) bagi faktor risiko adiksi secara umum (addiction-rf) yang menunjukkan poligenesitas tinggi. Dari semua leluhur yang diteliti, PDE4B signifikan (diantara gen lainnya), menunjukkan regulasi dopamine sebagai kerentanan lintas zat. Skor poligenik addiction-rf dikaitkan dengan gangguan penyalahgunaan NAPZA, psikopatologi, kondisi somatic, dan lingkungan yang terkait dengan munculnya kecanduan. Lokus spesifik zat (9 untuk alkohol, 32 untuk tembakau, 5 untuk ganja, dan 1 untuk opiat) melibatkan gen reseptor dan metabolik. Temuan ini memberikan wawasan mengenai lokus risiko genetik untuk gangguan penyalahgunaan NAPZA yang dapat digunakan untuk target pengobatan.
Resource Link
https://www.nature.com/articles/s44220-023-00034-y
Materials
- Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use
Alexander S. Hatoum, Sarah M. C. Colbert, Emma C. Johnson, Spencer B. Huggett, Joseph D. Deak, Gita A. Pathak, Mariela V. Jennings, Sarah E. Paul, Nicole R. Karcher, Isabella Hansen,
David A. A. Baranger, Alexis Edwards, Andrew D. Grotzinger, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Elliot M. Tucker-Drob, Henry R. Kranzler, Lea K. Davis, Sandra Sanchez-Roige, Renato Polimanti, Joel Gelernter, Howard J. Edenberg, Ryan Bogdan & Arpana Agrawal
Related Topics
- Biology/Neurobiology of Addiction
- Evidence-Based Practices
- Healthcare