Ambitious survey of human diversity yields millions of undiscovered genetic variants

A massive US programme that aims to improve health care by focusing on the genomes and health profiles of historically underrepresented groups has begun to yield results.

Analyses of up to 245,000 genomes gathered by the All of Us programme, run by the US National Institutes of Health in Bethesda, Maryland, have uncovered more than 275 million new genetic markers, nearly 150 of which might contribute to type 2 diabetes. The work has also identified gaps in genetics research on non-white populations. The findings were published on 19 February in a package of papers in Nature1,2Communications Biology3 and Nature Medicine4.

They are a “nice distillation of the All of Us resource — what it is and what it can do”, says Michael Inouye, a computational genomicist at the University of Cambridge, UK. “This is going to be the go-to data set” for genetics researchers who want to know whether their findings are generalizable to a broad population or apply to only a limited one, he adds.

Bridging the gap

Researchers have long acknowledged the lack of diversity in the genomes available for them to study, says Jibril Hirbo, a geneticist at Vanderbilt University Medical Center in Nashville, Tennessee, who studies the genetics of health disparities. One study5 that looked at data gathered up until January 2019 found that 78% of people in most large-scale genomic studies of disease were of European descent. This has exacerbated existing health disparities, particularly for non-white individuals, Hirbo says. When researchers choose genetic or molecular targets for new medicines or create models to predict who is at risk of developing a disease, they tend to make decisions on the basis of non-diverse data because that’s all that has been available.

The All of Us programme, which has received over US$3.1 billion to date and plans to assemble detailed health profiles for one million people in the United States by the end of 2026, aims to bridge that gap, says Andrea Ramirez, the programme’s chief data officer. It began enrolling people in 2018, and released its first tranche of data — about 100,000 whole genomes — in 2022. By April 2023, it had enrolled 413,000 anonymized participants, 46% of whom belong to a minority racial or ethnic group, and had shared nearly 250,000 genomes. By comparison, the world’s largest whole-genome data set, the UK Biobank, has so far released about half a million genomes, around 88% of which are from white people.

The All of Us data set is “a huge resource, particularly of African American, Hispanic and Latin American genomes, that’s massively missing from the vast majority of large-scale biobank resources and genomics consortia”, says Alicia Martin, a population geneticist at Massachusetts General Hospital in Boston.

In addition to the genomes, the database includes some participants’ survey responses, electronic health records and data from wearable devices, such as Fitbits, that report people’s activity, “making this one of the most powerful resources of genomic data”, Martin says.

An urgent need

A study in Nature on type 2 diabetes2 is an example of the power of using a database that includes diverse genomes, Ramirez says. The condition, which affects about one in ten people in the United States, can be caused by many distinct biological mechanisms involving various genes. The researchers analysed genetic information from several databases, including All of Us, for a total of more than 2.5 million people; nearly 40% of the data came from individuals not of European ancestry. The team found 611 genetic markers that might drive the development and progression of the disease, 145 of which have never been reported before. These findings could be used to develop “genetically informed diabetes care”, the authors write.

In another of the studies3, researchers used All of Us data to examine pathogenic variants — that is, genetic differences that increase a person’s risk of developing a particular disease. They found that, among the genomes of people with European ancestry, 2.3% had a pathogenic variant. Among genomes from people with African ancestry, however, this fell to 1.6%.

Study co-author Eric Venner, a computational geneticist at Baylor College of Medicine in Houston, Texas, cautions that there should be no biological reason for the differences. He says that the disparity is probably the result of more research having been conducted on people of European ancestry; we simply know more about which mutations in this population lead to disease. In fact, the researchers found more variants of unknown risk in the genomes of people with non-European ancestry than in those with European ancestry, he adds. This underscores the urgent need to study non-European genomes in more detail, Venner says.

Updating models

Gathering and using more genomic and health data from diverse populations will be especially important for generating more accurate ‘polygenic risk scores’. These provide a picture of a person’s risk of developing a disease as a result of their genetics.

To calculate a score for a particular disease, researchers develop an algorithm that is trained on thousands of genomes from people who either do or don’t have the disease. A person’s own score can then be calculated by feeding their genetic data into the algorithm.

Previous research6 has shown that the scores, which might soon be used in the clinic for personalized health care, tend to be less accurate for minority populations than for majority ones. In one of the current papers4, researchers used the more-inclusive All of Us data to improve the landscape: they calibrated and validated scores for 23 conditions and recommended 10 to be prioritized for use in the clinic, for conditions including coronary heart disease and diabetes. Martin applauds these efforts, but she hopes that future studies address how physicians and others in the clinic interpret these scores, and whether the scores can improve a person’s health in the long term because of the treatment decisions they elicit.

The All of Us programme plans to release a tranche of data every year, representing new enrolees and genomes, including one later in 2024, Ramirez says. It’s excellent that diverse data are coming in, Hirbo says, adding that he would like to see existing algorithms that were trained mainly on the genomes of people of European ancestry updated soon. “The models are still way behind,” he says.


World Social Forum in Kathmandu Calls for Peace and Justice Across Borders

Social advocates from 72 nations convened at the five-day World Social Forum (WSF) conference, which concluded on February 19 in Kathmandu, issuing a plea for the establishment of a world devoid of warfare.

The event, bearing the motto ‘Another World is Possible,’ kicked off on February 15 with a spirited rally involving 20,000 participants who paraded through the streets of Nepal’s capital, pressing for the liberation of Palestine, the eradication of slavery, casteism, fundamentalism, human trafficking, the empowerment of women, Dalits, and all marginalized groups.

A total of 252 seminars, workshops, and related sessions were organized by diverse human rights and social advocacy bodies from across the globe, tackling an array of subjects including climate justice, discrimination, secure migration, and the cessation of trafficking.

Approximately 9,000 individuals engaged in smaller group discussions, dissecting and reflecting on contemporary socio-political landscapes in various regions worldwide, and articulating statements advocating for unity, solidarity, and the revitalization of democratic values.

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Picture: Matters India

Indian representatives from numerous social and Christian organizations made a significant presence, with a notable turnout from Christian denominations, including Catholics and members of the World Council of Churches, who hosted seminars and workshops.

Among these, 60 members of the Forum of Religious for Justice and Peace from India, along with their 70 associates, led sessions focusing on themes such as environmental conservation, the protection of minority rights to foster an inclusive society, and ensuring safe and dignified migration.

During discussions on environmental stewardship, attendees deliberated on the degradation of natural habitats and ecosystems, water pollution, and the unsustainable exploitation of natural resources, advocating for a transition away from fossil fuels toward clean energy to sustain the web of life.

Calls were made for South Asian governments, particularly India and Nepal, to take decisive measures towards phasing out fossil fuels and transitioning to renewable energy sources. Additionally, developed nations were urged to compensate South Asian countries for the financial losses incurred during this transition, ensuring sustainable livelihoods for all, especially the most impoverished segments of society in the region.

Forum members and their collaborators listened attentively to accounts of persecution faced by minorities, particularly Christians, in India and Pakistan. Renowned Pakistani human rights activist Saeda Diep recounted various atrocities inflicted upon Christians, Hindus, Ahmediyas, and Shias in Pakistan, while Jesuit Father Bosco Xavier from India shed light on systemic discrimination based on ancestry and occupation worldwide.

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Picture: Matters India

The assembly condemned the prevailing atmosphere of xenophobia, exclusion, and violence targeting minority communities and those on the fringes of society, pledging to champion religious, cultural, ethnic, and linguistic diversity, which they regarded as integral to the region’s identity and deserving of respect and promotion.

In a joint statement, the forum demanded that South Asian governments, notably India, Pakistan, Bangladesh, and Sri Lanka, halt discrimination and violence against minorities and vulnerable groups, and instead, celebrate their distinctive cultural and religious heritage.

On the topic of safe and dignified migration, forum members affirmed the reality of extensive internal and international migration within South Asia driven by economic aspirations and conflict, emphasizing the need for robust legal protections for migrant workers and measures to shield them from discrimination and indignity.

Montfort Brother Varghese Theckanath, a forum participant, orchestrated a three-day International Tribunal on Evictions, wherein testimonies regarding forced displacement were presented. A panel of esteemed human rights activists from various continents rendered a verdict in favor of the rehabilitation of all displaced communities.

Forum national convener Presentation Sister Dorothy Fernandez, along with Congregation of Jesus Sister Ancy, Father Xavier, and Father Anand from the Indian Missionaries of Society, orchestrated various initiatives throughout the five-day event.

The program also featured a diverse array of cultural performances, with Bhrikuti Mandap, the event venue, resounding with Nepali melodies and dances, as well as musical renditions in various other Asian, African, South American, and European languages.

Each evening, Prerna Kala Manch, the theatrical arm of Vishwa Jyoti Communications in Varanasi, staged professional dramas addressing issues pertinent to farmers and minorities, captivating audiences with street plays that elucidated environmental concerns, discrimination, and communal strife.

Empowering Voices: ‘Women Who Win’ Unveils Inspirational Book Chronicling Diverse Journeys

In the midst of the 2020 pandemic, three women encountered a creative spark when they felt uninspired. Their response was to establish a platform aimed at uniting diverse women to foster inspiration and connection. This initiative, dubbed “Women Who Win,” commenced by inviting women worldwide to share their narratives, spanning business triumphs, personal development, conquered challenges, and surpassed obstacles.

In commemoration of their three-year milestone, the collective has unveiled its inaugural book. This publication chronicles a distinctive array of stories, with a central objective of empowering and resonating with readers on every page.

The book encompasses around 100 women, each voice compelling and every journey prompting profound contemplation in its own right. It endeavors to strike a chord with individuals from all backgrounds, featuring anecdotes from a broad spectrum of professionals including entrepreneurs, technologists, artists, community advocates, senior executives, young professionals, nonprofit leaders, healthcare providers, and change-makers of various stripes.

Highlighted personalities within the book encompass a diverse range, including Reshma Kewalramani, CEO of Vertex Pharmaceuticals; Swaroop Sampat, esteemed actress and educator; Jaishree Deshpande, philanthropist and co-founder of the Deshpande Foundation; Ami Ambani, businesswoman and avid marathoner; Chitra Banerjee, renowned Author; Annette Phillips, musician and singer from the Berklee India Ensemble; Gouri Banerjee, co-founder of Saheli Boston; Dr. Kavita Navani of Eclinical Works; Rosemarie Day, president of Day Health Strategies; Kay Khan, State Representative of Massachusetts; and Kathleen Walsh, president of YMCA Metro North, among others.

Shaleen Sheth, one of the co-founders of Women Who Win, expressed enthusiasm about the book’s inclusive representation, stating, “What excites me most is that the book includes the paths of women, coming from all different cultures and backgrounds, who are at the top of their field, and it highlights not only their successes but also the obstacles they faced along the way such as a health or family issue, or a career setback.” Sheth emphasized the importance of diverse narratives in guiding individuals through challenges and inspiring them to pursue ambitious dreams.

Dr. Deepa Jhaveri, another co-founder, echoed Sheth’s sentiments, remarking, “I love that this book encapsulates life – how some aspect of every life’s story is relatable to everyone.” She expressed hope that the stories would ignite readers’ aspirations and empower them to enact positive changes in their lives, whether in health, education, career, or personal growth.

Dr. Manju Sheth, MD, the third founder, highlighted the impact of the book’s focus on women’s health stories. Reflecting on the Wednesday Wellness series, Dr. Sheth emphasized the importance of preventative medicine and noted the positive response from readers, particularly in scheduling health screenings after reading firsthand accounts. She expressed satisfaction in potentially influencing individuals to prioritize their health.

The book, over a year in the making, has already sparked conversations and generated excitement both locally in New England and globally. Notable figures such as activist and actress Shabani Azmi have contributed to the book, with testimonials from esteemed individuals including philanthropist Desh Deshpande, Leader Bank founder and CEO Sushil Tuli, and Amruta Fadnavis, a banker, actress, singer, and social activist. The founders expressed gratitude to the women who entrusted them with their stories and anticipated celebrating with the community at launch events in Boston, New York, and India.

In a statement, the Women Who Win founders expressed their aspiration to make history by amplifying the voices of women and minorities, with the book serving as the first installment of a trilogy. They conveyed appreciation for the opportunity to spotlight the journeys of remarkable women and affirmed their commitment to this ongoing mission of empowerment and inclusion.

ADA Announces Diverse and Accomplished Leadership Team for 2024, Featuring Three Indian-Origin Experts

The American Diabetes Association (ADA) has disclosed its roster of principal officers and board of directors for the year 2024, a lineup that notably features three accomplished individuals of Indian origin. The ADA’s 15-member board, comprising professionals from the medical, scientific, education, and executive business realms, was detailed in a recent news release.

Among the distinguished appointees are Dr. Mandeep Bajaj, Dr. Rita Rastogi Kalyani, and Dr. Madi Rajulapalli, each bringing a wealth of expertise to the ADA’s leadership. Dr. Mandeep Bajaj, holding the position of president of medicine and science, serves as the vice chair for clinical affairs in the department of medicine and holds a professorship in medicine and molecular and cellular biology at the esteemed Baylor College of Medicine in Houston.

Dr. Bajaj occupies the role of chief of the endocrinology section at Baylor St. Luke’s Medical Center, concurrently acting as the medical director of the Baylor St. Luke’s Medical Center Diabetes Program and Baylor Medicine Endocrinology and Diabetes. His contributions extend beyond clinical roles, having served on the association’s scientific sessions meeting planning committee, finance committee, and research grant review committee. The ADA has acknowledged his exceptional contributions with the Outstanding Physician-Clinician award.

A graduate of the renowned All India Institute of Medical Sciences (AIIMS) in New Delhi, Dr. Bajaj pursued fellowship training in endocrinology and diabetes at the Joslin Diabetes Center in Boston. His impressive background and dedication to the field have positioned him as a respected figure within the ADA.

Dr. Rita Rastogi Kalyani, assuming the role of president-elect of medicine and science, is an associate professor of medicine in the division of endocrinology, diabetes, and metabolism at Johns Hopkins University School of Medicine in Baltimore, Maryland. Dr. Kalyani previously chaired the ADA’s professional practice committee, responsible for formulating the ADA standards of care in Diabetes in 2018. Her involvement with the ADA also extends to her presidency of the ADA’s Maryland community leadership board.

Currently serving as an associate editor for BMJ Open Diabetes Research and Care, Dr. Kalyani is a Harvard alumna, having earned her bachelor’s degree there. She completed all her medical training at Johns Hopkins, solidifying her academic and professional credentials.

Dr. Madi Rajulapalli, entrusted with the position of regional medical director for Medicare Case Management at CVS Health, boasts a distinguished career path. Before her current role, she served as the chief medical officer for Aetna Better Health of Louisiana and held leadership positions as the chief medical officer for provider-based health plans and population health, as well as chief medical officer for community healthcare centers.

Dr. Rajulapalli holds diplomas from the American Board of Internal Medicine and the American Board of Quality and Utilization Review Physicians. Her educational journey includes an MBA from Texas Woman’s University and executive education from Harvard Business School. Beyond her corporate responsibilities, Dr. Rajulapalli actively contributes to the ADA as the president of its board, Louisiana-Mississippi chapter. Additionally, she participates in the value-based care council—executive leadership advisory committee (EAC) for the National Association of Managed Care Physicians.

In her leadership role, Dr. Rajulapalli aligns with the ADA’s mission as a voluntary health organization committed to addressing the diabetes epidemic and enhancing the well-being of individuals living with diabetes.

The ADA, through its newly appointed principal officers and board members, continues to play a pivotal role in combating the challenges posed by diabetes. The inclusion of these three accomplished individuals of Indian origin underscores the organization’s commitment to diversity and excellence in its leadership. As the ADA strives to “bend the curve on the diabetes epidemic” and support those affected by the condition, the collective expertise of Dr. Bajaj, Dr. Kalyani, and Dr. Rajulapalli promises to contribute significantly to the organization’s ongoing efforts.