Lecture 8: Direct-to-consumer genetic testing

What is the difference in methodology between DTC genetic tests and clinical diagnostic genetic tests?

DTC tests use SNP arrays to “spot-check” specific DNA locations, whereas clinical tests use full-gene sequencing and deletion/duplicatoin analysis to examine the entire gene.

What percentage of disease variants reported in DTC raw data turned out to be false positives in clinical confirmation testing?

40% of variants in raw DTC data (especially in cancer susceptibility genes like BRCA1/2,TP53, and ATM)

Why should medical providers nerve make clinical management decisions based on DTC raw data alone?

Due to the 40% false-positive rate and high rates of variant misclassification by third-party interpretation tools.

what did twin studies reveal about consistency of DTC ancestry testing across different companies?

Identical twins show high ancestry agreement within the same company (~95-99%), but agreement drops significantly (52-84%) when comparing results across different companies.

What protections are provided by GINA (2008), and what major gap remains?

GINA protects against genetic discrimination in health insurance and employment, but does NOT protect against discrimination in life, disability, or long-term care insurance.

What ethical violation occurred in the Havasupai Tribe genetic research case?

DNA sample collected from the tribe specifically for diabetes research were used without permission for unapproved secondary studies on schizophrenia, inbreeding, and population migration.

How does a polygenic Risk score (PRS) differ from testing for a single gene mutation?

A single mutation has a large effect on one gene, whereas a PRS sums up the tiny cumulative risk contributions of thousands of common DNA variants across the entire genome.

What did the intern Health study discover regarding the major depressive disorder PRS (MDD-PRS) under stress?

MD-PRS was significantly more predictive of depression during intense internship stress than at baseline, and individuals in the lowest 2.5% tail of MDD-PRS showed high resilience against stress-induced depression.