Kuldeep Kumar, Ph.D. | Blog

A small structural interval upstream of TACR3 looks, at first, like a hormone locus. But read through a neuroimaging lens, it becomes more interesting: DRAGEN-WGS, Garg 2026 AJHG, and Big40-Oxford all point toward a coherent bilateral striatal MRI signal. This post focuses on that hidden neuroendocrine–striatal story and what it reveals about structural variation in brain imaging genetics.

Two decades ago, Chenn & Walsh showed β-catenin sets cortical size; later work established APC as its Wnt-pathway antagonist. GWAS caught the pathway — but never these two genes individually, and never with a cell type. The first genome-scale, whole-brain, in-vivo Perturb-seq atlas quietly supplies the missing piece, in a structure and life-stage the classic work never reached.

Brain organoids offer a controlled window into how genomic dosage alters early human neurodevelopment. Using 16p11.2 and recent cross-mutation organoid studies as examples, this post asks what these models genuinely add to CNV, psychiatric, and neuroimaging genetics—and where their evidence should stop.

Reflections from The Neurobiology of Mental Health meeting at Lake Thun: a rare gathering where developmental neuroscience, psychiatric genetics, brain atlases, white matter, organoids, circuits and therapeutic translation flowed into one connected scientific story.