On a deck overlooking Lake Union, the founder of my previous company pitched an idea to a group of us. What if there were people walking around in robust health while carrying a gene thought to condemn them to severe childhood disease? These people should be very sick, but aren’t. Finding those people and investigating what’s protecting them would be very interesting.

This idea went by the name of the Resilience project. Here’s how Mount Sinai Professor Ron Chen’s site describes it. “The Resilience Project aims at finding individuals with rare genetic mutations that the medical text books would indicate should have caused catastrophic illness but somehow these individuals are ‘resilient’ – they have been protected via yet to be discovered genetic or environmental factors.”

Analyzing over a half-million genomes, they found 13 individuals with apparent resilience to Mendelian diseases. Protective variants were not totally unknown previously. See Modifier genes in Mendelian disorders: the example of cystic fibrosis.

Now, at least one start-up has been created to capitalize on the idea. In February, Maze Therapeutics announced a $191 million series A funding round. Based in South San Francisco, the company is led by Charles Homcy along with scientific team including:

  • Mark Daly, geneticist at the Broad, leader of Finland’s Finngen project.
  • Sekar Kathiresan, advocate for clinical use of polygenic risk scores.
  • Stephen Elledge, geneticist and biochemist at Harvard Medical School.
  • Aaron Gitler, professor of genetics at Stanford University.
  • Jonathan Weissman, professor at UCSF.
  • Matt Brauer, former bioinformaticist at Genentech.

The hope is that modifier genes may hold the secret to new drugs.

Maze is working with public(-ish) datasets. The Nature Biotech article, Unicorn startup trawls databases for protective genetic modifiers, included this handy table of large genetics data sets:

Table 1 | Selected population genetics initiatives

Project (year established)

Goal

Funders

Partners, participants

DeCode Genetics, a subsidiary of Amgen (1996)

DeCode has whole-genome sequence data on about 15% of Iceland’s population and genotype data from about 50%, which it combines with clinical and genealogical data from Iceland and open-source data from around the globe for biological discovery

Amgen

SomaLogic

China Kadoorie Biobank (2004)

Blood samples collected from over 510,000 individuals from 2004–2008; analyses combined with clinical and mortality data, as well as biological data from periodic follow-up studies

Kadoorie Charitable Foundation, Wellcome Trust, Chinese Natural Science Foundation, Chinese Ministry of Science and Technology, British Heart Foundation, Cancer Research UK

Chinese Academy of Medical Sciences, Oxford University

UK Biobank (2006)

Prospective cohort study involving collection and analysis of genetic, physical and health data on 500,000 people aged 40–69 at time of recruitment

Medical Research Council, Wellcome Trust

Regeneron is leading exome sequencing, with support from AbbVie, Alnylam Pharmaceuticals, AstraZeneca, Biogen, GlaxoSmithKline and Pfizer; data are available to 10,000 approved industry and academic researchers

Million Veteran Program (2009)

Collecting blood samples, health, military experience and lifestyle information from one million US military veterans to study the genetic factors that influence health

US Department of Veterans Affairs Office of Research & Development

Veterans Affairs-affiliated researchers

Regeneron Genetics Center (2014)

Has sequenced 400,000 exomes of 500,000-exome target; combining genetic data with electronic health record data

Regeneron Pharmaceutica

Geisinger Health System, US National Institutes of Health, academic medical centers

Genomics Medicine Ireland (Dublin), a subsidiary of WuXi NextCode (Shanghai) (2015)

Combining medical and health data with sequence data from 400,000 genomes (>10,000 completed so far); studies in rare and chronic diseases ongoing

Arch Venture Partners, Ireland Strategic Investment Initiative, Polaris Partners, Temasek Holdings, Yunfeng Capital, Sequoia Capital

AbbVie, University College Dublin, University of Cambridge, hospitals in Ireland and Northern Ireland, UK

All of Us (formerly Precision Medicine Initiative Cohort Program) (2016)

Building a research database containing biological, physiological, environmental and health data from over one million people who reflect the diversity of the US population

US National Institutes of Health; US National Cancer Institute

Accredited academic and industry researchers, as well as interested citizen scientists, will have access to a research portal

Kaiser Permanente Research Bank (2016)

Aims to collect biological samples from 500,000 members, which it will combine with electronic health records, lifestyle and environmental data

Kaiser Permanante

Kaiser Permanante and accredited researchers

FinnGen (2017)

The University of Helsinki is responsible for the study, which involves the collection of genome and longitudinal clinical data from 500,000 individuals through a nationwide network of biobanks, universities and hospitals

Business Finland, industry partners

AbbVie, AstraZeneca (Cambridge, UK), Biogen, Celgene, Genentech, GlaxoSmithKline (London), Merck, Sanofi (Paris), Pfizer